A free left atrial ball thrombus is relatively a rare diagnosis and usually leads to systemic embolization or fatal complication of thrombus incarceration in left ventricle inflow. We report a case of 52-year-old woman who was admitted to hospital with symptoms of heart failure. Routine echocardiography showed a free-floating ball thrombus in the left atrium. The free-floating thrombus was round with smooth surface and about 37 mm in diameter. The mitral valve prosthesis was well-functioning. The computed tomography of the patient also showed the left atrial ball thrombus. The erratic finding was that the patient was compliant on oral anticoagulants for the last 6 months with her INR in theraputic range. This suggested that this thrombus had been there for a some time and anticoagulants failed to resolve this problem. She was referred to cardiac surgery for thrombus extraction but the patient refused to have the operation. This case report includes the clinical and echocardiographic signs of a free ball thrombus discovered in the left atrium in a patient who had undergone mitral valve replacement nine years previously. Free-floating ball thrombus usually leads to catastrophic complications of thrombus incarceration in left ventricle inflow and sudden death3. The presence of free-floating thrombus also leads to higher embolic potential4.The incidence of free-floating ball thrombus in the left atrium is quiet rare5, however anticoagulation long term role in prevention of thrombus recurrence is evident.4Anticoagulation and thrombolytic therapy seem to have no role in the immediate management of left atrial free thrombi and surgical extraction remains the first choice treatment A 52-year-old woman, who had a bi-leaflet mechanical prosthesis placed in the mitral position 9 years previously, was admitted to hospital because of paroxysmal dysnea, orthopnea, generalized edema and easy fatigability for 2 weeks. She had never before experienced embolic manifestation or syncopal attacks. She was maintained on a regimen of adequate anticoagulation with warfarin (12 mg). The international normalized ratio was 3.6 on day of admission.At time of hospital admission, she was in New York Heart Association (NYHA) class 4 and in atrial fibrillation (AF) with rapid ventricular response. Her blood pressure was 100/70 mmHg. She was given furosemide 40 mg IV to relieve pulmonary congestion and digoxin 0.5 mg IV to control the heart rate. On auscultation, the prosthetic valve click was normal, bilateral medium-sized crepitations were heard over the chest wall. An ECG revealed AF with rapid ventricular rate of 120 b/m and poor R progression in the chest leads. The chest radiograph showed cardiomegaly, left-atrial enlargement, biventricular enlargement, and pulmonary venous congestion . TransthThe relatively large size of the thrombus, compared to mitral prosthesis orifice, seemed to protect the patient from systemic embolization of the thrombus. Computed tomography of the chest also revealed the left atrial ball thrombus  and 3b. 1. Although rare, early detection & management is important because of its potentially fatal complications 6.Thrombus formation in the left atrium can occur as either an early or late complication of mitral valve replacement, but the presence of ball thrombus, freely floating in the left atrium without attachment to the mitral valve prosthesis or the atrial wall, is very rare2. Mural thrombus slowly increases in size to become a projecting mass connected to the atrial wall through a pedicle. The bulbous part of the thrombus becomes more bulky, with progressive deposition of fibrin and platelets, and the pedicle thins out and finally detaches or breaks down into multiple small fragments, causing systemic embolization events. Ball thrombus freely rotates in the dilated left atrium with a characteristic smooth fine surface6.Ball thrombus usually originates as a mural thrombus adherent to the interatrial septum and to a lesser extent to atrial appendages2.The reason for the typical spherical or oval shape of free ball thrombi remains unclear. It has been suggested that this configuration comes from fresh clot being layered out concentrically as it spins around the atrium1 .The movement of the thrombus results in a ping-pong effect characterized by sudden acceleration due to the impact of the mitral leaflets during ventricular systole. A floating rotatory movement within the left atrial cavity, and a rotation of the thrombus on its own axis that does not follow the cardiac cycle, are highly suggestive of a ball-valve thrombus6. Our patient demonstrated none of these features, and an echocardiogram was necessary to reveal the presence of a free-floating thrombus. The diagnosis of a free floating thrombus in echocardiography is based on two criteria: the thrombus must be bigger than the cross sectional area of the valve orifice, so that it is locked up within the atrium, and it should have a smooth surface with no attachment to the atrial wall7.Clinical diagnosis is difficult, but LA free thrombus should be suspected if patients with mitral stenosis, or mitral valve prosthesis, and atrial fibrillation have intermittent or changing murmurs, embolic manifestations and syncope. Variations in symptoms have also been associated with changes in the position of the patient1. Anticoagulant and thrombolytic therapy do not appear to play a role in the acute management of left atrial ball thrombus5.Diagnosis of a free-floating ball thrombus necessitates emergency surgery with simultaneous treatment of the underlying cause. Surgery produces a long-term survival rate of more than 90%The datasets used during the current study are available from the corresponding author on reasonable request.The author reports no conflicts of interest.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.


Soft tissue perineurioma of the kidney is rare, with only a few reported cases. We report two additional cases with histologic, immunohistochemical and genetic analyses.MDM2 and rearrangements of ESWR1, FUS, and KMT2A. Targeted next-generation sequencing revealed a low tumor mutation burden and likely pathogenic mutations (CYP2B6 and FLT1 mutations for 1 each). Follow-up data were available for both patients; neither had tumor recurrence or metastasis.Both tumors were from adults  and grossly had maximum diameters of 6.5 and 10 cm, respectively. The tumors were overall well circumscribed but unencapsulated, with focally entrapped benign native renal tubules in one case; both tumors seemed to arise in the capsular areas. The tumors had histologic and immunohistochemical profiles consistent with soft tissue perineurioma. Fluorescence in situ hybridization analyses demonstrated that the tumors were negative for amplification of In conclusion, renal perineurioma is rare, usually arises in the capsular areas, and is cured by resection. Low-grade dedifferentiated liposarcoma and low-grade fibromyxoid sarcoma as well as other spindle cell lesions should be considered in the differential diagnosis. NF2 or deletions of 17q11 (including NF1)[Perineurioma is a rare and usually benign peripheral nerve sheath tumor composed entirely of cells resembling normal perineurium that includes soft tissue, intraneural, sclerosing and reticular variants , 2. Softding NF1).Soft tissue perineurioma mostly affects the superficial soft tissues of the extremities and trunk, with approximately 30 % developing in deep soft tissue and very rarely in visceral locations . Soft tiA previously healthy 49-year-old female patient was admitted to the hospital due to incidental discovery of a solid mass in the left kidney by abdominal ultrasound. A computed tomography (CT) scan showed a sharply defined, heterogeneously enhancing mass involving the upper pole of the left kidney measuring 5.7 cm×4.0 cm in size Fig. A. With tGross examination of the resection specimen revealed a well-demarcated, round and whitish tumor with solid and firm texture (6.5 cm×5.0 cm×4.0 cm) Fig. B. MicrosMDM2  for 425 cancer-relevant genes (Gene seqPrime) revealed a low tumor mutation burden (TMB) (1.1 mutations per megabase) and a likely pathogenic mutation of CYP2B6 (NM_000767.5) at chromosome 19:41,515,212 of exon5 c.734T > C, which has a variant allele frequency (VAF) of 25.0 %  at chromosome 13:28,964,050 with exon 13 c.1852 A > T, which has a VAF of 1.5 %  of renal perineurioma in English-language publicationsReferenc. CompareWith regard to soft tissue perineurioma of the kidney, the differential diagnoses were broad and principally included neurofibroma, schwannoma, solitary fibrous tumor, and spindle cell predominant angiomyolipoma in the kidney. Familiarity with its unique morphological features, including storiform or whorled arrangements of slender spindle cells with delicate bipolar cytoplasmic processes with wavy or tapering nuclei, supplemented by the frequent immunoexpression of EMA, claudin-1 and GLUT1 as well as absence of expression of S100 protein, SOX10, STAT6, HMB45, and SMA/desmin, can usually distinguish renal perineurioma from the other entities mentioned above.MDM2 and CDK4) amplification, the genetic hallmark of DDLPS, can serve as a robust tool to distinguish DDLPS from soft tissue perineurioma.Clinically, the most important differential diagnosis is from low-grade dedifferentiated liposarcoma (DDLPS) and low-grade fibromyxoid sarcoma (LGFMS), both of which can extend into and become secondarily involved in the kidney as a primary tumor in the retroperitoneal regions. DDLPS by definition is an atypical lipomatous tumor/well-differentiated liposarcoma showing transition to nonlipogenic sarcoma, which in most cases is of high grade and uncommonly exhibits low-grade histologic features . Low-graFUS-CREB3L2 fusion in approximately 75 % of cases. Rare cases harboring fusion variants of FUS-CREB3L1 and EWSR1-CREB3L1 have been described [FUS/EWSR1-CREB3L fusion harbored a novel YAP1-KMT2A fusion, potentially expanding the genetic spectrums of these related tumors. In case 1 of our report, MUC4 was expressed in less than 10 % tumor cells, raising the suspicion of LGFMS. However, positivity for CD34 by IHC, which is very uncommon in LGFMS, and negativity for rearrangements of FUS and EWSR1 by FISH analyses excluded the possibility of LGFMS. Both our cases were negative for KMT2A rearrangements, which can further help with differentiation.Perhaps the closest histologic mimic of soft tissue perineurioma of the kidney is LGFMS, which arises most commonly in deep soft tissue of the extremities and occasionally in the abdominal cavity and retroperitoneum . LGFMS iescribed . MUC4, aescribed . In a stescribed , MUC4 waescribed found thaNF2 are the most frequently reported genetic abnormalities. Deletion of 17q11 (including NF1) is also a recurrent event in a subset of cases [NF1 and NF2, in both tumors, which revealed low levels of TMB and likely pathogenic mutations with CYP2B6 and FLT1 mutations for 1 each; however, no genomic alterations in NF1 or NF2 were identified. CYP2B6, located at 19q13.2, is a polymorphic detoxification gene that plays a vital role in the degradation of genotoxic compounds. Single nucleotide polymorphisms in the CYP2B6 gene locus, which result in reduced enzymatic activity, have been associated with many types of solid tumors, mainly hematological malignancies [FLT1, also known as vascular endothelial growth factor receptor-1 (VEGFR-1), is located at 13q12.3 and encodes a member of the VEGFR family. VEGFR family members are receptor tyrosine kinases and serve as critical mediators of tumor angiogenesis and vessel permeability. VEGFR-1 has been detected in schwannoma, and increased levels of this factor correlate with increased rates of tumor growth [CYP2B6 and FLT1 have not been reported in soft tissue perineurioma, and the pathogenic significance of these mutations is largely unknown. It is worth collecting more cases for further in-depth study to determine whether these are novel potential pathogenic mutations in soft tissue perineurioma.Cytogenetically, soft tissue perineurioma shares similar pathogenic mechanisms with those of other nerve sheath tumors. Deletion of 22q12 and mutations in of cases . In the r growth . MutatioIn summary, soft tissue perineurioma rarely arises from the kidney and is usually located in the capsular areas. Although atypical histologic features such as local invasive growth can be seen, the clinical behavior is benign. Low-grade DDLPS and LGFMS as well as other spindle cell lesions should be considered in the differential diagnosis.


Despite mostly indolent course and favorable postoperative outcome long‐term follow‐up studies are needed to identify the most appropriate therapeutic strategies to minimize surgical morbidity and neurologic injury in patients with RGNT. Despite mostly indolent course and favorable postoperative outcome long‐term follow‐up studies are needed to identify the most appropriate therapeutic strategies to minimize surgical morbidity and neurologic injury in patients with RGNT. Two months following radical resection of the tumor the patient succumbed due to postoperative complications.Rosette‐forming glioneuronal tumor (RGNT) is a rare, slow‐growing, mixed neuroglial neoplasm of the central nervous system with a predilection to the fourth ventricle region.RGNT affects young to middle‐aged adults with a variable female predominance, according to some authors up to 2:1.A MEDLINE and PubMed searches for terms “rosette,” “forming,” “glioneuronal,” and “tumor” were performed in December 2019 and non‐English articles were excluded. All relevant publications and related articles were scrutinized for RGNT. To our knowledge, about 150 cases have been described in the English literature to present time.Originally, the location of the RGNT was described as arising exclusively in the fourth ventricle, the vermis, and the cerebellum. However, recent reports show that RGNTs may occur outside the characteristic locations, such as spinal cord, optic chiasm, tectum, pineal gland, third ventricle, cerebellopontine angle, and hypothalamus.The spectrum of symptoms is wide and depends on the size and the exact location of the lesion. It includes headache, dizziness, ataxia, dysarthria, blurred vision, vomiting, hemiparesthesia, tinnitus, neck pain, diplopia, nausea, somnolence, hand tremor, anisocoria, and cranial nerve palsy..On computed tomography (CT), RGNT presents as a hypodense mass lesion with/without microcalcifications.RGNT usually presents on magnetic resonance imaging (MRI) as iso/hypointense on T1‐weighted and hyperintense on T2‐weighted images with limited mass effect and surrounding edema. To a variable amount, it may be enhanced after contrast administration; however, the enhancement is usually nonhomogeneous, rather focal and minimal.Microscopically, the tumor displays a typical biphasic morphology; cellular areas with neurocytic rosettes and perivascular pseudo‐rosettes and paucicellular glial areas. Occasionally, Rosenthal fibers of ganglion cell dimension, eosinophilic granular bodies, microcalcifications, and dysmorphic neurons of ganglion cell dimension may be found in glial areas. Necroses and mitoses are usually absent. Immunohistochemically, the glial fibrillary acidic protein (GFAP) is positive in glial component, while cores of neurocytic rosettes and neuropil of perivascular pseudo‐rosettes are immunoreactive to synaptophysin. The proliferation index (Ki‐67) does not precede 1%.Clinically and morphologically, RGNT must be differentiated from pilocytic astrocytoma, other low‐grade gliomas with piloid glial component, hemangioblastoma, and glioneuronal tumors arising from the floor of the fourth ventricle or inferior cerebellum.Despite the usual favorable postoperative course and prognosis in terms of survival, the location may prevent complete surgical removal, presents a significant risk of neurologic injury and extends postoperative deficits.2A 34‐year‐old Caucasian male with unremarkable medical history was urgently admitted to the Department of Neurosurgery with a 2‐month history of progressively worsening morning headaches accompanied by nausea and vomiting. The pain did not disappear completely after analgesic use and was followed by numbness, tingling sensations and muscle power loss in his upper extremities. Occasionally, the patient also experienced foggy or double vision, vertigo, and clumsy gait. Neurological examination showed both vertical and horizontal nystagmus, accompanied with gait ataxia. Cranial nerve functions were normal.Head CT showed a hypodense mass lesion occupying the central part of the posterior cranial fossa, measuring 30 × 40 × 40 mm. The lesion did not demonstrate any contrast enhancement. No calcifications were noticed within the lesion. Surrounding edema of the brain parenchyma and hydrocephalus were identified Figure .MRI revealed an abundant, relatively well‐demarcated tumor mass in the fourth ventricle Figure  causing The patient underwent a suboccipital midline craniotomy with total resection of the tumor. Several tan and gray fragments of the lesion were submitted for frozen section (FS) and further histopathological examination. On FS examination, the tissue was mostly hypocellular. On one edge of the examined sample, the cellularity was focal slightly pronounced; there were small, uniform, and bland nuclei arranged in a circle‐like fashion. Mitotic activity, necroses, and endothelial proliferation were not present Figure . The repThe remaining tumor tissue was formalin‐fixed and embedded in paraffin. The microscopic examination of Hematoxylin & Eosin (H&E) stained sections revealed typical features of a RGNT. The major component of the tumor was represented by neurocytes with small, round, regular nuclei with speckled chromatin and scant cytoplasm forming rosettes with central eosinophilic neuropil material and perivascular pseudorosettes. The counterpart of the neurocytic component was a paucicellular astrocytic component, which consisted of fibrillated spindle and stellate cells with elongated or oval nuclei. Very rare microcalcifications were present and there was no evidence of necrosis, mitotic activity, endothelial proliferation, or nuclear atypia. Ganglion cells and Rosenthal fibers were absent too. Occasional eosinophilic granular bodies were seen Figure .The glial fibrillary acidic protein (GFAP) was immunoreactive in glial component, but absent in rosettes and pseudorosettes. Synaptophysin was positive in the central areas of neurocytic rosettes and in the neuropil of perivascular pseudorosettes, which, on the contrary, did not show any immunoreactivity for the GFAP Figure . The Ki‐Immediately after surgery, the patient was awake and cardio‐circulatory stable with Glasgow Coma Scale (GCS) score 15. About eight hours after surgery, he went into cardiac arrest with PEA  and was successfully resuscitated after more than 10 minutes. However, his pupils were widened and unreactive, he was completely unresponsive (GCS score 3) and hemodynamically unstable with irregular tachyarrhythmia and hypotension. Generalized brain edema and small (12 mm) epidural suboccipital hematoma on the right side were present on a control CT scan and decompressive suboccipital craniectomy was performed. Despite intensive therapy, the patient remained in an unresponsive state with signs of hypoxic encephalopathy on several CT scans. Brain death test results were positive. He died due to pneumonia two months later. An autopsy was performed. Microscopically, the whole brain tissue was avital and no tumor remnants were found.3RGNT is rarely encountered tumor occurring in the fourth ventricle.RGNT is a grade 1 tumor entity included in the WHO 2016 Classification of Tumours of the Central Nervous System. According to this classification, RGNT is defined as “a slowly growing neoplasm that affects preferentially young adults, occurs predominantly in the fourth ventricle, can also affect other sites as pineal region, optic chiasm, spinal cord, and septum pellucidum and is composed of two distinct histologic components: one with uniform neurocytes forming rosettes and/or perivascular pseudorosettes, the other being astrocytic in nature and resembling pilocytic astrocytoma”.The lesion has also been documented in other midline locations within the cerebellum, brain stem, third and lateral ventricles, pineal gland, and hypothalamus.The histogenesis of RGNT is, to date, unclear. The presumed origin of the RGNT is the pluripotent cells of the subependymal plate , which have also been suggested as the site of origin of DNTs of the cerebellum.It is not known yet whether this finding reflects the normal or aberrant developmental site of precursor or stem cells. The increasing numbers of RGNTs, reported in locations other than the fourth ventricle, cannot exclude the alternate possibility of histologically similar tumors with underlying genetic differences. Although it may resemble a pilocytic astrocytoma, there are no MGMT promoter methylation and no BRAF‐V600E alteration, fusion, as well as mutation, present in either the rosette‐forming or the glial regions of the tumor.The rarity of the lesion and therefore the lack of experience represent a great challenge for the pathologist examining the frozen section (FS) of the RGNT. The location of the lesion, the age and the sex of the patient are helpful data; however, the most important is the biphasic morphology of the lesion. Hypo‐ and hypercellular areas, presence of circle‐like structures made of small, uniform, and bland nuclei, the absence of nuclear atypia, endothelial proliferates, and necroses are the clue to a proper FS diagnosis.Pilocytic astrocytoma, other low‐grade gliomas with piloid glial component, DNT, oligodendroglioma, central neurocytoma, and glioneuronal tumors arising from the floor of the fourth ventricle or inferior cerebellum should be included in the clinical and morphological differential diagnosis of RGNT. The most difficult tumor to differentiate from RGNT is pilocytic astrocytoma, especially if only the astrocytic component is present in the tissue sample. However, pilocytic astrocytoma can be differentiated from RGNT by the absence of rosettes or perivascular pseudorosettes. DNT is typically a supratentorial tumor that presents in younger age group. Oligodendrogliomas with neurolytic differentiation may show neurocytes or even well‐formed rosettes; however, they occur in older age, include oligodendroglial components, and generally arise in frontal lobe. Neurocytoma lacks the biphasic pattern—small round cells forming rosettes are present, yet there is the absence of astrocytic components in the tumor.RGNTs are benign brain tumors with the possibility of malignant transformation and IDH‐1 mutation.Our case elucidates the need for possible changes in surgical techniques to minimize surgical morbidity and neurologic injury in these benign tumors especially before they could progress locally, transform into malignant and become occlusive. Could the use of the stereotactic‐guided Gamma Knife or stereotactic laser‐induced thermotherapy (LITT) be reasonable in RGNT patients as well? Should the prior biopsy help the surgeon in planning the surgical procedure? Do we have to test all RGNTs for IDH‐1 mutation or should this testing be reserved only for cases with frankly malignant transformation? Long‐term follow‐up studies are needed to answer these questions and to identify the most appropriate therapeutic strategies to diminish severe and disabling postoperative neurological deficits in patients with RGNT.In summary, RGNT is considered a rare, mostly low‐grade tumor entity with distinct radiological, histological, and immunohistochemical features. Although it was initially described as a strictly fourth ventricle lesion, other locations are possible to dictate the clinical symptoms and the choice of treatment. RGNT should always be considered in differential diagnosis with other infratentorial lesions, especially in young adults. Despite mostly indolent course and favorable postoperative outcome, the experience with this tumor remains limited.The authors declare no conflict of interest.TV: involved in conception, design and preparation of the manuscript, acquisition, analysis and interpretation of the gathered data, and critically revised the manuscript.JR: involved in acquisition of the clinical data, performed the surgical procedure, and critically revised the manuscript. RK—the corresponding author— analyzed the histopathological slides  and signed out the final biopsy report, involved in conception, design and preparation of the manuscript, analysis and interpretation of the gathered data, microphotography, and critically revised the manuscript.The authors declare human ethics approval was not needed for this study.


We describe a case of a patient who presented with a mildly symptomatic, giant myelolipoma which was excised by laparoscopic approach without complications.Adrenal myelolipoma (AML) is a rare tumour composed by fat and myeloid tissues. Usually it is asymptomatic, so the diagnosis is mostly incidental. It is generally located in the right adrenal gland, but it can also be found bilaterally. If its size exceeds 10 cm it is defined as a “giant myelolipoma”; in this case its treatment of choice would be adrenalectomy with an open surgical approach.Patient's signs and symptoms were mild pain in the right hypochondrium and a positive right Giordano's sign. The mass was detected by a contrast-enhanced CT scan. Once excised it measured 16 cm.Laparoscopic adrenalectomy for giant myelolipoma is a safe approach if performed by an expert surgeon, with low risk of bleeding and a better outcome for the patient. •Literature evidences are scarce regarding the surgical management of giant adrenal myelolipomas.•Laparoscopic surgery is safe and feasible even for adrenal lesions larger than 10 cm.•Clear resection margins can be obtained even for massive adrenal tumors. Both sexes are equally affected by AML, mainly in the fifth-sixth decade of life. It is a rare tumour with an incidence of 0.08–0.2% at autopsy It is frequently diagnosed incidentally, given its asymptomatic nature. Its diagnosis has become simpler and more frequent thanks to the widespread use of imaging studies like Ultrasonography (US), computed tomography (CT), and Magnetic Resonance Imaging (MRI). If its diagnosis cannot be certified with imaging, and hence malignancy suspicion remains, a fine needle biopsy should be performed Adrenal myelolipomas were first described by Gierke in 1905 AML is a rare tumour AML is a benign mesenchymal tumour with different cell types, mainly adipocytes and haematopoietic cells, which include erythroid and myeloid elements. They are not extramedullary sites of haematopoiesis Most commonly myelolipomas are found in the right adrenal gland, but it can also be found bilaterally. Sometimes they were described in the presacral area, stomach, spleen, liver, lung and testes Rarely it presents with unspecific abdominal symptoms like pain, abdominal discomfort, nausea, vomiting, weight loss, diarrhea, and dyspepsia, most of them for its mass effects, impinging on the surrounding organs; some patients experience episodes of haematuria or signs of internal haemorrhage. As they grow larger than 10 cm in diameter, they could rupture spontaneously. Although, according to Meyer et al. there isn't correlation between symptoms and the dimension of the tumour Recently, the widespread use of imaging studies increased the detection of AML On MRI, instead, the fatty component is usually hyperintense on the T1-weighted images and heterogeneously hyperintense on the T2-weighted images However, MRI doesn't help in carrying out the diagnosis of adrenal myelolipoma in patients with unclear CT findings, and, thereof, needle biopsy could be helpful in such difficult cases Conservative approach is usually preferred as treatment strategy. However, if symptomatology ensues, mass growth increases speedily, or if presents as greater than 6 cm, adrenalectomy will be the main indication. In fact, the potential risk of malignancy and retroperitoneal haemorrhage would be substantial.Thereby, the mainstay of surgical treatment of giant myelolipomas is radical adrenalectomy through an open surgical approach 2A 61-year-old Caucasian male was admitted to our General Surgery Department for a two-month persistent pain in the right hypochondrium, with no other relevant symptomatology. His medical history included hypertension, obesity , aortic valve replacement with bio-prosthesis performed in 2018 for severe aortic valve stenosis.Preoperative abdominal US revealed a mass bigger than 10 cm with a heterogeneous appearance. It appeared mainly hyperechoic with hypoechoic islets, interposed between the lower hepatic margin and the upper renal pole. Vascularization at colour-Doppler sonography was non-significant.A contrast-enhanced abdominal CT scan confirmed the presence of a voluminous (14 × 12 cm) encapsulated neoformation composed of mainly adipose tissue in the right adrenal lodge. It arose from the medial branch of the right adrenal gland, in contiguity with the upper third of the right kidney, which appeared dislocated and partially horizontalized on its major axis a, b.Fig.Laboratory data showed normal hormonal levels: aldosterone 40.60 pg/ml [37–432 pg/ml]; serum cortisol 10.1 μg/dL [3.7–19.4 μg/dl], adrenocorticotropic hormone 17.60 pg/mL [≤46 pg/ml]; dehydroepiandrosterone sulfate 91.90 μg/dl [48.6–361.8 μg/dl]; renin 10.10 microUI/ml [5.3–99.1 microUI/ml]; 24-h urinary metanephrines 111.84 microg/24 h [0–374.99] and normetanephrines 326.77 microg/24 h 0–779.99. Dexamethasone suppression test revealed adequate decrease of serum cortisol <1 μg/dL. Abdominal physical examination was unremarkable. All radiological features showed no signs of malignancies. However, due to patient's discomfort a laparoscopic procedure was performed. Under general anaesthesia, an anterior transabdominal approach using four trocars was carried out. Our patient was placed in a left flank position with a 45 ° side tilt. The optical trocar (11 mm) was inserted on the intersection between the trans-umbilical and periumbilical lines. The liver retractor trocar (11 mm) was placed subxiphoidally on the paraumbilical line. The last two trocars (11 mm and 5 mm) were positioned at the level of the mammary line, respectively in the subcostal and right iliac regions. During dissection, the tumour had a red-brown pigmentation, due to the presence of focal areas of haemorrhage. After right adrenalectomy, the specimen was placed in an Endopouch inserted through a Pfannenstiel incision .Fig. 2PoHistological examination revealed a large encapsulated adrenal myelolipoma measuring 16 × 12 × 6 cm and weighing 634 g .Fig. 3SuThe operative time (OT) was of 160 min and no clinical intra-or postoperative complications occurred. Laboratory data after surgery didn't present any alteration and no laboratory signs of post-operative complications were observed.On the 1st postoperative day (POD) the patient was mobilized. Oral feeding was initiated 2 days after surgery and on the 4th POD the abdominal drain was removed. The patient was discharged in good general condition on the 5th postoperative day. At 6 month-follow up no signs of recurrence were detectable.3Treatment for adrenal masses is required for lesions with the following features: clinically relevant, hormonally active, or large in size. The risk of malignancy for adrenal masses increases to 25% in lesions bigger than 6 cm, therefore this is the surgical cut-off value. Small, non-functioning tumors should be managed via annual radiological follow up while the ones greater than 7 cm should be removed. Instead, giant myelolipomas (greater than 10 cm) are even more commonly associated with intraoperative complications, such as bleeding, capsular breach and a higher risk of local recurrence Open radical adrenalectomy is the standard treatment for giant myelolipomas or in emergency cases wherein haemorrhage or rupture occur, while the minimally invasive approach is preferred for small AML The first laparoscopic adrenalectomy was described by Gagner in 1992 Only few cases of giant myelolipomas were treated with minimally invasive adrenalectomy 4Very scarce evidence can be found in the literature regarding the laparoscopic surgical approach of giant adrenal masses. The gold standard yet remains the open surgical approach, however thanks to the improvements of minimally invasive techniques, we have presented a case wherein this approach can be considered safe and feasible. Furthermore, clear resection margins and a 6-month negative follow up can be achieved.No source of funding.Not applicable.Written informed consent was obtained from the patient for this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.Not commissioned, externally peer-reviewed.Dr. Tinozzi Francesco Paolo, MD.Not applicable.Dr. Tinozzi Francesco Paolo, MD Study design, study concept, data collection, final approval of the version to be submitted, surgical operationDr. Morone Giovanni, MD Study design, study concept, data collection, data analysi, surgical operationDr. Benedetto Calì, MD, Study design, study concept, data collection, data analysis, writing the articleDr. Rebba Andrea, MD, Study design, study concept, data collection, data analysis, writing the articleDr. Osman Nadine, MD, study concept, data collection, data analysisDr. Albertario Simone, MD, study concept, data collection, data analysisDr. Abbiati Francesca, MD, study concept, data collection, data analysisDr. Ruggiero Rubina, MD, Study design, study concept, data collection, surgical operationNo conflict of interest is present.


Primary synovial chondromatosis, or Reichel's syndrome, is a rare benign tumour arising from the synovial lining of a joint. We present the case of a 25-year-old male with Reichel's syndrome of the ankle, with subsequent recurrence following open retrieval of loose bodies. The initial presentation was of lateral malleolus discomfort which limited moderately strenuous exercise. Clinical examination showed a mild effusion and pain on extremes of movement. Imaging confirmed the presence of multiple loose bodies within the anterior and anterolateral recesses of the ankle. Open removal of 27 loose bodies from the joint was performed, with good postoperative recovery. He represented with pain 9 months later, with imaging of the ankle showing reaccumulation of loose bodies to a lesser extent. A trial of conservative management was opted for. Reichel's syndrome confined to the ankle is an exceedingly rare diagnosis, with few cases reported in the literature. This case saw the recurrence of the disease in a short time period despite successful surgery in the first instance. Management options to treat recurrence include repeat retrieval of foreign bodies, synovectomy, radiotherapy, or arthrodesis. While the prognosis is favourable, a low risk of malignant potential warrants adequate patient follow-up. Synovial chondromatosis (SC) is a rare benign tumour arising from the synovial lining of a joint . This syA 25-year-old male student presented with persistent discomfort over the lateral malleolus following an uncomplicated twisting inversion injury of the ankle 3 months prior. The pain was responding to bandage compression and simple analgesia, however was limiting moderately strenuous exercise. On examination, there was full range of movement at the ankle in all directions, with discomfort on maximal dorsiflexion and eversion. A mild effusion of the ankle joint was appreciated compared to the contralateral side. No ankle deformities or overlying skin changes were appreciated. The patient was previously healthy, on no regular medication. He smokes and drinks only socially. Routine blood investigations taken recently had been unremarkable.An x-ray was performed on first presentation which demonstrated multiple globular calcified loose bodies in the anterior aspect of the joint, in keeping with suspected synovial chondromatosis . No fracMagnetic resonance imaging of the ankle joint was performed to better visualize the lesions .This confirmed the presence of multiple variably sized loose bodies within the ankle, primarily in the anterior and anterolateral recesses. The lesions were of indeterminate signal intensity on T1 and proton dense fat saturated images with a thin sclerotic rim. The largest loose body was 12 mm. The ankle and subtalar articular surfaces were normal with no evidence of osteochondral lesions or tarsal coalition. The visualized bones and ligaments were unremarkable.Open removal of 27 loose bodies from the anterior gutter was performed, with the larger bodies sent for analysis . An openThe patient represented 9 months later, as he was once again experiencing ankle discomfort for the past two weeks. A repeat x-ray of the affected joint showed the reaccumulation of loose bodies, however to a much lesser extent . Once agPrimary synovial chondromatosis (SC), or Reichel's syndrome, most commonly affects adults with a typical age presentation of 30 to 50 years and a predisposition towards males . RadioloWhile SC is typically a benign condition, there have been reports of malignant potential in the form of synovial osteochondroma, at an estimated rate of 5% , 5. DistThere is a scarcity in the literature of case series demonstrating SC confined solely to the ankle; however, the prognosis tends to be favourable –9. PatieThe management options for primary SC, as well as disease recurrence, are limited. Conservative management has been documented for asymptomatic patients or those not experiencing bothersome symptoms . Repeat Primary synovial chondromatosis confined to the ankle is an exceedingly rare diagnosis, with only a low volume of cases reported in the literature. Our case saw the recurrence of disease in a relatively short period despite complete removal of loose bodies in the first instance. Management options to treat recurrence include repeat open or arthroscopic retrieval of foreign bodies, synovectomy, radiotherapy, or arthrodesis. While the prognosis is favourable, a low probability of malignant potential should not be overlooked and thus patients warrant adequate follow-up.


Undifferentiated embryonal sarcoma (UES) is an uncommon paediatric hepatic tumour that clinically simulates a liver abscess when present with fever. This report describes a case of UES in a 12-year-old boy, who presented with abdominal pain, swelling and fever, all simulating a liver abscess. The possibility of UES was considered at imaging, based on the solid appearance on ultrasound and cystic appearance with serpiginous peripheral vessels on computed tomography/magnetic resonance imaging. The diagnosis was confirmed at histopathology. Additionally, some patients present with intermittent and low-grade fever, making it difficult to distinguish from a liver abscess or a complicated hydatid cyst.2 However, an accurate diagnosis is essential to initiate appropriate management. Imaging features can be variable; however, a peculiar paradoxical appearance on imaging, that is, solid on ultrasonography (USG) and cystic on CT or MRI, can help in the early diagnosis of this entity.4 Presented here is a case of UES of the liver in a 12-year-old boy who presented with abdominal pain, right-sided upper abdominal bulge and low-grade fever, masquerading as a liver abscess.Undifferentiated embryonal sarcoma (UES) of the liver is a rare malignant hepatic tumour of mesenchymal origin. It is primarily seen in children between 6 and 10 years of age.A 12-year-old boy was admitted with complaints of mild abdominal pain and fever for one month. The intermittent and low-grade fever was relieved with analgesics. The mild and dull aching abdominal pain was confined to the right hypochondrium without any radiation. He also complained of a right upper abdominal bulge. There was a history of decreased appetite and weight loss of about 2–3 kg. The patient was haemodynamically stable. On abdominal examination, a firm and mildly tender mass was palpable 10 cm below the right costal margin, and the mass was not separately palpable from the liver. No prior history of hydatid disease, malignancy or any other comorbidity was found.At USG, a large well-defined mass was found in the right lobe of the liver. It was solid and iso to hyperechoic in appearance with a few cystic areas . No appaFollowing failure to respond to antibiotic therapy, contrast-enhanced CT (CECT) and CE-MRI were requested for further evaluation of the lesion. Contrast-enhanced CT demonstrated a cystic appearing mass (attenuation: 20–25 HU) with peripheral internal vascularity  and b. MA core needle biopsy was performed under USG guidance, using an 18G semi-automatic gun; however, the pathology was inconclusive because of the predominant necrotic material obtained during the biopsy procedure. Microbiological analysis of the biopsy sample was negative for bacteria, fungi, Entamoeba and parasites. Due to the non-resolving condition and inconclusive diagnosis, the patient finally underwent a right hepatectomy with removal of the lesion approximately 16 days after hospitalisation. The resected specimen revealed a large soft and friable tumour. The cut surface of the specimen revealed components of haemorrhage, necrosis and gelatinous material. There were no intra-operative or postoperative complications, and the patient was discharged on the 11th postoperative day in a stable condition.Histopathological analysis of the resected specimen indicated that the tumour was composed of sheets of spindle cells with cellular pleomorphism, indistinct cytoplasm and hyperchromatic nuclei. Immunohistochemistry showed CD10 membrane positivity, vimentin reactivity in spindle cells and negativity for Myo D1. These findings were suggestive of UES.Postoperatively, the patient received six cycles of chemotherapy (vincristine + cyclophosphamide + epirubicin). He was asymptomatic with no recurrence on the last follow-up at 11 months after surgery.1 Undifferentiated embryonal sarcoma is most commonly seen between 6 and 10 years of age; however, it has been reported in adult patients as well.5 Clinical manifestations are usually non-specific. Children present with abdominal pain, loss of appetite and weight and a mildly tender abdominal lump. Some patients may have fever and elevated leukocyte counts which cause difficulty in differentiating it from other hepatic pathologies, such as a liver abscess or complicated hepatic hydatid cyst.3 In a recent case series of 10 patients, fever was one of the manifestations in eight of 10 patients.6 A few patients present to the emergency department with acute abdominal pain because of tumour rupture and bleeding.2Undifferentiated embryonal sarcoma is an uncommon malignancy of undifferentiated mesenchymal cells. It accounts for only 0.1% of surgically resected primary liver masses.6Unlike other common paediatric hepatic tumours such as hepatoblastoma and hepatocellular carcinoma (HCC), AFP levels are usually not elevated in UES, which is an additional clue to its diagnosis. Alternatively, LDH levels can be elevated in about 70% – 75% of cases; however, the cause is still unclear.7 Characteristically, imaging shows a paradoxical appearance. On USG, UES shows solid-dominant mixed echogenic areas with variable anechoic cystic areas; however, it often appears as a cystic lesion with low attenuation on CT. This discrepancy in appearance is attributed to myxoid tissue, which usually appears hyperechoic on USG.4 A similar appearance was also seen in the patient presented. At times, lesions may be predominantly anechoic with multiple septa, simulating benign tumours such as mesenchymal hamartoma and biliary cystadenoma.8 Nodular solid components and septations are also not uncommon, which show delayed enhancement.3 This case showed serpiginous vessels along the periphery of the lesion which has also been described in a previous study by Gabor et al. Serpiginous vessels were found in 9 of 15 patients in their study.3 Undifferentiated embryonal sarcoma often shows areas of haemorrhage, and MR signal varies depending on ages of the bleeds. Hyperintense signal on T1W images with fluid-fluid levels can occur because of internal haemorrhage and necrosis. Haemorrhagic ascites or perihepatic fluid may be seen in cases of tumour rupture.8 Neither was found in our patient.The imaging appearance of UES may be inconsistent, varying from entirely cystic to entirely solid.8 Rhabdomyosarcoma is an alternative differential; however, it arises from the biliary tree and causes biliary obstruction, unlike UES.8Mesenchymal hamartoma is the most common imaging differential as both share common imaging features. Although age may not be a reliable element, age < 2 years usually favours mesenchymal hamartoma and age > 5 years, usually favours UES. Additionally, intralesional haemorrhage and serpiginous vessels favour UES.6 Another lesion that closely mimics UES on imaging is a hydatid cyst, especially in endemic regions. A complicated hydatid cyst can present with fever.9 Amoebic serology, hydatid serology and fluid analysis may provide clues to the specific diagnosis.Clinically and radiologically, UES simulates a liver abscess, particularly when fever and leukocytosis are present.8 A hepatic tumour in a child < 5 years old that shows lower enhancement than the adjacent hepatic parenchyma and elevated serum AFP levels is more likely to be hepatoblastoma. Hepatocellular carcinoma usually arises on a background of diffuse parenchymal liver diseases, such as glycogen storage disorders, tyrosinemia, Wilson’s disease, etc.10 Hepatocellular carcinoma appears as an arterially hyperenhancing mass with washout during the portal venous or delayed phases of imaging. It is commonly seen in children > 5-year-old.10 Various salient features of the differential diagnoses of UES are summarised in 12Hepatoblastoma and HCC rarely have a cystic appearance; however, AFP levels are often elevated in these tumours, unlike UES, where the AFP level is often normal.13 Image guidance helps procure a biopsy sample from the viable part of the tumour with a higher diagnostic yield and is also associated with a lower complication rate. An 18G biopsy needle suffices in most instances.3 However, because of the predominantly cystic nature of UES, percutaneous biopsy may not provide representative tissue and an open biopsy may be required for diagnostic confirmation.13 A definitive diagnosis of UES is made only on histopathology, supported by immunohistochemistry.7Collection of inadequate specimens or sampling error usually leads to an incorrect histological diagnosis which often occurs in this condition because of the predominance of tumour necrosis and haemorrhage.15 Although there is no universal consensus regarding the management guidelines, complete resection of the tumour and combined adjuvant chemotherapy is the standard treatment strategy.15 Liver transplantation may be an option for patients with unresectable tumours. Imaging plays a vital role in post-treatment follow-up. It helps in the assessment of treatment response and to detect tumour recurrence early.13In the past, the postoperative recurrence rate was high. However, advancement in current treatments has substantially improved the clinical outcome with a lower rate of recurrence.The peculiar paradoxical appearance of a paediatric liver lesion, that is, solid on USG and cystic on CT/MRI, should raise the possibility of UES, especially in the presence of normal AFP levels, serpiginous vessels and intralesional haemorrhage.


Clostridium perfringens, other clostridia, and non-clostridia bacterial species producing gas. Unlike classical gas gangrene or myonecrosis, the disease develops without a wound or a port of entry. Instead, gas-producing bacteria in the gastrointestinal tract colonize an underlying pathological process with foci of necrosis, producing excessive gas and spreading hematogenously to other organs. Herein we present two autopsy cases of primary hepatic gas gangrene diagnosed on autopsy, with the gross and histological changes that can be considered specific for this rare condition. Both patients had severe underlying liver disease-prone for this entity development. The gross changes in the cases are postmortem subcutaneous emphysema, skin bullae with pooled blood, pneumothorax, pneumoabdomen, abundant gas in the circulatory system, porous structure of the internal organs (tissue gas bubbles), and advanced tissue lysis, not corresponding to the post mortem time. Histology showed optically empty areas of varying size in the internal organs, which weave the structure of the organs and rod-shaped bacteria with scarcity or complete absence of inflammatory reaction.Primary hepatic gas gangrene is a form of primary abdominal gas gangrene. The condition is caused by  Clostridium perfringens and is most commonly associated with soft tissue infections of the extremities after trauma.-,-Gas gangrene is an infection caused predominantly by The patient was a 62-year-old caucasian male complaining of dizziness, headache, and nausea, without vomiting. Previous medical history included type 2 diabetes mellitus for 23 years, hypertension, ischemic heart disease, chronic renal failure, and benign prostate hyperplasia. Laboratory tests are summarized in Due to the neurological symptoms, the patient was referred to a neurological evaluation which reported severe dysphonia, dysarthria, dysmetria, decreased spinal reflexes, and a positive Babinski reflex. The patient was referred for brain computer tomography (CT). However, the patients' condition deteriorated. The accompanying neurologist reported a Glasgow coma scale of 3 points, and a perceived shock condition was suspected. Cardiopulmonary resuscitation (CPR) was initiated without success. The patient was pronounced dead thirty minutes after the initial presentation.A 62-year-old caucasian female sought medical care in a severely deteriorated clinical condition with complaints of general malaise, dyspnea, abdominal pain, and vomiting over the last three days prior. Previous medical history included breast cancer with liver metastases. Laboratory tests are summarized in Both patients showed elevated levels of serum glucose, creatinine, and c-reactive protein (CRP). A more detailed list of laboratory parameters is shown in Both autopsies were performed within eight hours after the death. Both patients had a body mass index (BMI) of more than 35. Subcutaneous crepitations corresponding to subcutaneous emphysema were noted in both patients in all topographical areas. Abdomen and lower limbs showed skin bullae, some of which with pooled blood  and 2.Rigor mortis had been set in both patients across all muscle groups except the palmar muscles. On section, free gas, under pressure, was present in the subcutaneous tissue and the thoracic and abdominal cavities. Therefore, a probe for gas and air embolism was attempted. Still, upon filling the pericardial pouch with water and severing the cardiac chambers, large gas bubbles were released from all four cardiac chambers. Both patients had gross changes associated with hypertension - cardiomegaly (cardiac weight 520 g (mean reference range [mRR] 302 g);, left ventricular thickness 19mm  and right ventricular thickness 7mm  in the first patient, and in the second case the cardiac weight was 440g , left ventricular thickness 17mm  and right ventricular thickness 5mm , and hypertensive nephrosclerosis.All internal organs were greyish, soft, and cross-sections revealed a porous surface most pronounced in the liver and spleen. In addition, both patients had enlarged steatotic livers, with multiple metastases in the second case.rigor mortis.All organs seemed to have undergone severe autolysis, not corresponding to the time elapsed after death and the presence of In Case 1, other gross changes worthy of note were a small polypoid tumor of the cecum, and in case 2, multiple liver metastases were present.Specimens of all internal organs were obtained and preserved in 10% buffered formaldehyde for histological evaluation.Histopathology from both cases revealed a porous composition of the organs, with varying pore size, from small to medium and large optically empty areas dissecting the architecture of the organs and artificially weaving its structure. These correspond grossly to gas-filled bubbles. In most of these optically empty areas, free rod-shaped bacteria and rod-shaped bacterial colonies could be seen, as well as rod-shaped bacteria in the adjacent tissue, with a paucity or complete lack of inflammatory cells. In both patients, the most severely affected organ was the steatotic liver , 4.In both cases, similar changes were observed in multiple organs, namely the spleen, pancreas, gastrointestinal tract mucosa, kidneys, and myocardium , 6.In both cases, additional unterated to the gas gangrene findings were cardiomyocyte hypertrophy, with scant interstitial myocardiosclerosis, arteriolohyalinosis, and sclerosis in the kidneys (with glomerulosclerosis) and brain, corresponding to hypertension, as well as fibrosis and lipomatosis of the pancreas.In both cases, the treating physicians were consulted for the presence of the bullae and subcutaneous emphysema. In both cases, they confirmed these changes were not present antemortem.rigor mortis was still set. Underlying conditions for development were considered severe steatosis in the first patient and multiple hepatic metastases from the mammary carcinoma in the second patient.The hepatic gas gangrene diagnosis was established based on the fulminant clinical course, gas-filled bubbles throughout the organs, and advanced lytic changes, while ,,Primary hepatic gas gangrene and primary abdominal gas gangrene are rapidly fatal and underreported conditions, difficult to recognize and treat clinically.,,-,,,The postmortem interpretation in such cases should be cautious and detailed. The physicians treating the patients' should be consulted for the postmortem development or progression of subcutaneous emphysema, bullae, and the presence of localized organ symptoms, or if present imaging investigations such as computer tomography (CT) or abdominal ultrasound.,,,-,,The site of primary development in the liver and adjacent structures is likely due to clostridia and other gas-producing bacterial species in the gastrointestinal tract (GIT).,,,,,,,Postmortem microbiological isolation of clostridia and other gas-producing bacteria can be of aid.,,-,-Clinically although difficult to suspect and diagnose, a combination of abdominal CT or ultrasound do identify gas collections in parenchymal organs as well as microbiological identification of clostridia, and antimicrobial treatment has been reported to still be with high mortality due to the progressive nature of the condition.Primary hepatic gas gangrene, as a form of primary abdominal gas gangrene, is a rare condition, difficult to diagnose clinically and with high mortality. However, the two autopsy cases presented herein underline the gross and morphological changes of the internal organs, which can be considered specific in the first 48 hours postmortem.


Solitary bone plasmacytoma (SBP) is a rare manifestation of plasma cell tumor. Although axial skeleton is the most frequently affected site of SBP, adjacent disc space involvement is rare. Herein we report a case of SBP in thoracic vertebra with involvement of adjacent disc space.A 57-year-old male presented with a 2-year history of intermittent back pain with activity. The patient's back pain intensity with activity was a score of 5 of the 10-point visual analog scale).The patient underwent a posterior fusion procedure from T6 to T10, and an open biopsy of the vertebral lesion confirmed that final diagnosis of SBP. The patient received postoperative radiotherapy with a total of 4000 Gy to the T7–T9 vertebral levels over a 20-day period.Following radiotherapy, the patient's pain intensity was reduced to the visual analog scale score of 1 at the 6-month follow-up.SBP lacks typical clinical symptoms, and the accurate diagnosis before clinical intervention remains challenging. Due to the disc involvement, SBP often manifests as spinal infection. Hence, differential diagnosis in spinal lesions involving the disc should include SBP. The presentation of vertebral lesion with adjacent disc space involvement usually indicates spinal infection, whereas the possibility of an SBP involvement is rarely considered. We here report a case of SBP in the thoracic spine involving an adjacent disc space, and its differential diagnosis from spinal infection.The most common complaint of patients with spinal disease is back pain, which has a series of underlying causes such as infection and neoplasm. Differentiating these causes of back pain is important to diagnosis and medical management. This case report described a patient presented with back pain caused by a solitary bone plasmacytoma (SBP). SBP is characterized by a localized proliferation of neoplastic plasma cells in the absence of significant bone marrow plasma cell infiltration, which occurs primarily in red marrow-containing bones such as vertebrae, femurs, pelvis, and ribs.2The Institutional Review Board and Ethic Committee of Shandong Province Chest Hospital and the 960th Hospital of Joint Logistics Support Force of PLA approved the proposal of this investigation.Written informed consent was obtained from the patient for this case report to be published .3A 57-year-old male was admitted with a chief complaint of intermittent pain in the back for the past 2 years. The pain was nonradiating and not responding to conservative medical management. The patient's pain intensity score was 5 on a 10-point visual analog scale. He had no symptom of sensorimotor neuropathy. The severity of the neurologic deficit was defined as “E” according to the American Spinal Injury Association Impairment Scale. His medical history and findings from physical examinations were unremarkable. His routine blood tests were within normal range and the urine analysis showed normal values. Old tuberculin test and brucellosis agglutination test were negative. His lateral spine radiograph showed osteolytic destruction from T7 to T8 vertebrae with intervertebral space stenosis. Computed tomography (CT) revealed slight expansile osteolytic destruction at T8 with sclerosis margin, extended to the T7 and T9 and adjacent disc space destruction. Magnetic resonance imaging (MRI) showed the lesion centered in the T8 vertebral body extending to T7 and T9 with disc space destruction. The lesion was mildly isointense on T1-weighted images, hyperintense on T2-weighted images, and homogeneously enhanced on T1-weighted post contrast images Fig. . ImmunohPostoperative fluorodeoxyglucose-positron emission tomography/CT showed that the T7-T9 lesion was fluorodeoxyglucose avid with standard uptake value of 10.9, and no other suspicious hypermetabolic lesions Fig. . Based o4 The median age at the diagnosis is 55 years and males are more frequently affected than females. The lesion is often present for many years as a single lesion; however, it can eventually progress to multiple myeloma (MM). Currently, regional radiotherapy continues to be the recommended treatment for SBP at a dose of 40 to 50 Gy over approximately 4 weeks. The response rate to radiotherapy has been shown to be 94%. The adjuvant chemotherapy did not affect the incidence of progression of SBP to MM, but it did delay the progression from 29 to 59 months. Ultimately, 53% of patients with SBP develop MM within 17 years of treatment, and 14% develop local recurrence within 5 years of treatment.,6,7SBP is a rare hematologic malignant disease, which is defined by the presence of a single osteolytic lesion due to monoclonal plasma cell infiltration, with or without soft-tissue extension.,9 Diagnostic criteria of a SBP include pathological proven solitary lesion, normal bone marrow with no evidence of clonal plasma cells, normal skeletal survey and MRI (or CT) of spine and pelvis (except for the primary solitary lesion), and absence of end-organ damage. Our case meets all these criteria for the diagnosis of SBP. Several studies have reported that patients complained back pain on average 8 months before the diagnosis of SBP. In those cases, patients visited various health care services on multiple occasions leading to the SBP diagnoses; some even received incorrect diagnoses.,11 Imaging studies play an important role in the diagnosis, treatment, and prognosis. However, imaging studies may not always provide a conclusive diagnosis. SBP has an osteolytic appearance on plain radiographs, and an expansile osteolytic lesion with marked enhancement on CT or MRI. SBP of spine could show curved coarse trabeculae with hypertrophic sclerosis, forming “mini brain sign” which may have certain characteristics. This appearance may be correlated with the less aggressive nature of SBP comparing with other malignant tumors that aggressively destroy the bone with no radiological evidence of bone repair features such as sclerosis and thickening.,13 In our case, we could not observe this similar imaging feature. To the best of our knowledge, most studies did not report the imaging presentation of SBP involving adjacent disc space. In fact, only in 1 case of SBP, involvement of the adjacent disc space (by direct extension) was reported. Afonso et al reported a 41-year-old woman with SBP, her spine CT revealed areas of destruction in both the vertebrae and discs between T12 and L2. That case report mainly focused on CT and MRI findings, and did not offer differential diagnosis of spinal neoplasms and infections in the involved vertebrae and associated disc spaces.The most common site of SBP is in the vertebrae, especially in the thoracic vertebrae. Back pain is a common clinical feature due to lesion compression.,15 However, 1 study found that 2% malignant spinal lesions involved vertebral discs. SBP with adjacent disc space destruction of the patient may be due to aggressive traits of primary plasmacytoma infiltrating and destructing adjacent bones, muscles, fats, and vascular encasements.,18 In spinal lesions involving adjacent disc spaces, the differential diagnosis should include neoplasm and bacterial infection tests. In some conditions of spinal infection, patients can be afebrile with nonspecific symptoms, and imaging findings can be nonspecific or atypical. Laboratory examinations including white blood cell count, erythrocyte sedimentation rate and C-reactive protein are inconclusive,20 and biopsy is warranted to establish diagnosis. However, a study reported that the presumed etiology in 18% of the cases was not confirmed on pathological examination. A recent meta-analysis reported the sensitivity of CT-guided percutaneous needle aspiration biopsy was 52.2%  for the diagnosis of spinal infections. The presentation of disc involvement is a nonspecific feature of spinal infection, and can be SBP, as is shown in our case. Hence, differential diagnosis between spinal neoplasm and infection could be more difficult and complicated. The diagnostic approach for the patients of spinal lesions with disc involvement should include a complete medical history, physical examination, and necessary laboratory examinations and imaging evaluations during which possible risk factors for infections and neoplasm must be investigated and identified. It is important to recognize the imaging findings as the signs of spinal neoplasm and infection, and a short-term follow-up imaging examination should be performed to detect any changes. In some cases, repeat or open biopsy may be required as it is the only reliable method to distinguish neoplasm versus infection.Usually, spinal lesions associated with a poorly defined vertebral body endplate, involvement of intervertebral disc space, presence of paravertebral abscesses, and involvement of two contiguous vertebral bodies are suggestive of spinal infection. On the contrary, spinal lesions associated with a well-preserved disc space, destroyed vertebral bodies with solid extraosseous soft tissue, skip or nonconsecutive multifocal involvement of spine are suggestive of spinal neoplasm.5In conclusion, our case illustrated atypical imaging features of SBP with disc involvement. The imaging feature of disc involvement may be difficult to differentiate from spinal infection. Importantly, we conclude that differential diagnosis of spinal SBP with disc involvement and spinal infection relies mainly on the combined application of imaging examination and its correlation with clinical history and laboratory tests. Due to limited literature available, our case report may help to recognize this rare sign of SBP with disc involvement, thus avoiding misdiagnosis and mistreatment.Conceptualization: Gang Sun.Data curation: Hongdong Tan, Jia Gu, Liang Xu.Investigation: Jia Gu, Liang Xu.Methodology: Hongdong Tan, Jia Gu.Supervision: Gang Sun.Writing – original draft: Hongdong Tan, Gang Sun.Writing – review & editing: Hongdong Tan, Gang Sun.Hongdong Tan: data collection and analysis, MRI and manuscript writing; Liang Xu: data curation; Jia Gu: pathology; Gang Sun: conception and design and manuscript writing.


Retroperitoneal intravenous leiomyomatosis is a rare benign tumor that can spread through veins carrying significant morbidity. The challenge of its management lies within the complexity of completely excising the tumor, which if carried out improperly can result in neurological or vascular complications requiring complex reparative surgeries. Here we present the successful resection of a retroperitoneal angio-leiomyoma by combining laparoscopic route, micro-surgical techniques and modern endoscopic tools.The online version of this article (10.1007/s13224-020-01404-7) contains supplementary material, which is available to authorized users. Intravenous leiomyomata (IVL) are rare benign vascular neoplasms characterized by intraluminal growth of smooth muscle into either venous or lymphatic vessels outside the limits of myoma. Uterine IVL can extend through the veins, with inferior vena cava extension or pulmonary and heart metastasis, carrying significant morbidity –3. RetroA 35 year-old patient with two children underwent laparoscopic retroperitoneal pelvic tumor excision at the Dubai London Clinic and Speciality Hospital. The patient presented with chronic left leg pain for many years. At admission, ultrasound examination and MRT image findings were described as a mucinous cystadenoma of the left ovary (9.2 × 5.6 cm with relative irregular outline and filling the pouch of Douglas), with the differential diagnosis of a broad ligament leiomyoma with intrinsic tumor degeneration and necrotic features. By combining laparoscopic route, in-bag morcellation and micro-surgical technics, it was possible to ensure complete resection of the retroperitoneal tumor without intraoperative vascular or neural complications Below is the link to the electronic supplementary material.


To report a rare case of isolated intraconal meningioma. A 24-year-old woman presented with painless proptosis in her left eye whichstarted and progressed during her pregnancy about 10 months ago. Hertelexophthalomometry revealed anterior displacement of the globe with 4 mm ofproptosis which was remarkable. Magnetic resonance imaging (MRI)demonstrated an intraconal circumscribed oval-shaped mass with hypointensesignals on T1-weighted images and hyperintense signals on T2-weightedimages, mimicking cavernous hemangioma. This mass, however, was free of anyconnections to optic nerve or bones. Due to the imaging characteristics,more prevalent diagnoses like cavernous hemangioma were placed on the top ofthe differential diagnoses list. However, during the surgical excision, thetumor’s consistency and gross features were not compatible with cavernoushemangioma. The pathologic findings instead determined meningotheliomatousmeningioma, a very rare condition, which was far from our expectations priorto the surgery.Ectopic orbital meningiomas are rare tumors that are not easily diagnosedwithout postoperative histopathology. Despite its low prevalence, theyshould be considered in the differential diagnosis list of intraconal masseswith hypointense signals on T1-weighted images and hyperintense signals onT2-weighted images. These lesions are furthersubdivided into three classifications. The first classification is primary opticnerve sheath meningiomas (ONSM) originating from the arachnoid layer of the opticnerve  intraconal meningioma.Orbital meningiomas account for 0.4–2% of all meningiomatous tumors.A 24-year-old woman presented with painless proptosis in her left eye, which startedand progressed during her pregnancy about 10 months ago. Her uncorrected- andbest-corrected visual acuity (UCVA and BCVA) were 20/25 and 20/20, respectively. Inaddition, the relative afferent pupillary defect (RAPD) in the left eye wasnegative. While the Hertel exophthalmometry revealed an anterior displacement of theglobe with 4 mm of proptosis, the fundoscopy showed a left optic disc edema. Otherslit-lamp examinations were normal.Magnetic resonance imaging (MRI) demonstrated an intraconal circumscribed oval-shapedmass with hypointense signals on T1-weighted images and hyperintense signals onT2-weighted images [Figure 1] mimicking cavernous hemangioma.As a consequence, the patient underwent uncomplicated superomedial orbitotomy whichresulted in the removal of a 3A histopathological examination showed tumoral cells with syncytial and whirlingarrangement, indistinct cell membranes, eosinophilic cytoplasma, and rather uniformnuclei. Some intranuclear pseudoinclusions were also present. Mitotic figures wererare. Immunohistochemistry revealed positive staining for epithelial membraneantigen (EMA) a progesterone receptor (PR) [Figure 2] and negative staining forS100, CD34, and BCL2. Ki67 showed proliferative activity in about 1–2% of tumorcells. As a result, a meningotheliomatous meningioma (WHO grade 1) diagnosis wasmade.Postoperative radiotherapy was performed on the orbital tumor bed. After a one-yearfollow-up, no complications or changes in the patient's perimetry, visual acuity,and RAPD were detected.When assessing an intraconal mass with hypointense signals on T1-weighted images andhyperintense signals on T2-weighted images, several differential diagnoses should beconsidered, such as cavernous hemangioma, schwannoma, lymphoma, and neurofibroma. Inour case, the orbital mass was intraconal without connections to the optic nerve orbones. Due to the imaging features of the lesion, a more prevalent diagnosis, suchas cavernous hemangioma was expected. However, during the surgical excision of thelesion, the tumor's consistency and gross features were different from that of acavernous hemangioma and the pathological evaluation of the mass determinedmeningotheliomatous meningioma.As a result, our patient underwent an orbitotomy with a partial tumor resection dueto its fragile nature. Systemic work up was normal and the patient was referred foradjunctive radiotherapy. Although recurrence is rare in cases of complete excision,it should be mentioned that incisional biopsy has been known to accelerate spreadingand recurrence of the tumor. were ruled out in our case.It should be mentioned that other possible diagnoses such as sclerosis or hyperplasiaof the superior orbital rim or asymmetry of the sinuses Origin of ectopic meningiomas hasalways been debated. These tumors may originate from congenitally dislocated nestsof meningothelial cells, regressed orbital meningoceles located within the orbit, orcuriously associated with dislocated meningeal tissues into the orbit secondary topenetrating injury or trauma.Interestingly, several reports exist regarding extracranial or extraduralmeningiomas found in unusual sites such as the neck, skin, finger, lung,mediastinum, and adrenal gland.Orbital meningiomas most commonly arise from the base of skull or optic nerve sheathwhile ectopic orbital meningiomas are extremely rare accounting for Lee Teak Tan et al reported a case of presumed ectopic orbital meningioma which wasdecidedly diagnosed as olfactory groove meningioma. As a consequence, hehypothesized that a number of the previously reported cases have had similarscenarios of misdiagnosis. Having said that, other distinguished researcherscontinue to consider ectopic meningioma as a distinct entity where the origin andexistence of ectopic orbital meningioma is still being debated.To date, there have been few reports of intraconal ectopic meningioma cases. A briefreview of some of the recent reports of ectopic meningioma cases and other relatedissues such as demographic data, history, imaging findings, treatment, and finaloutcomes are summarized in Table 1. As a consequence, future case would need to be monitoredto ensure all avenues are investigated.The unique aspect of this case which has not been reported in prior studies is thedevelopment of an ectopic meningioma during pregnancy. This coincidental discoveryon the possible association between pregnancy and the development and enlargement ofmeningiomatous tumors currently has no precedence and hence no available supportingdata. However, it is recommended that treatment of these tumors be executed toensure prevention of focal aggression.In summary, as ectopic orbital meningiomas are characteristically very rare tumorsand are not easily diagnosed with orbital imaging because of similar resemblance toother intraorbital tumors, serious consideration should be made in ensuringexecution of postoperative histopathology to determine the existence or absence ofthese low prevalent tumors. The possible occurrence of these meningiomas should alsobe considered in the differential diagnosis of intraconal masses with hypointensesignals on T1-weighted images and hyperintense signals on T2-weighted images. Thisapproach would ensure the accurate diagnosis of conditions and would encourage theappropriate course of treatment.Nil.There are no conflicts of interest.


Fistulas are an abnormal connection between two or more epithelial surfaces. When fistulization between adjacent structures occurs in the pelvis, there is almost invariably significant associated morbidity and impact on a patient’s quality of life. Imaging may aid in the diagnosis of pelvic fistulas and is essential to identify any associated pathology, define the course of the fistula, and aid in pre-surgical planning.This article aims to review the wide array of clinical and imaging presentations of fistulas in the pelvis, with a focus on the radiologists’ role in managing this challenging entity.This article will review each classification type of fistula.Pelvic fistula is a devastating condition that causes significant morbidity and evaluation can be challenging.Imaging, and particularly MRI, plays a vital role in the diagnosis, characterizing the course of a fistula and demonstrating associated complications, which are essential to guide treatment decisions. Fistulas are an abnormal connection between two or more epithelial surfaces. When fistulization between adjacent structures occurs in the pelvis, there is almost invariably significant associated morbidity and impact on a patient’s quality of life. This is exacerbated by the difficulty of diagnosing pelvic fistulas clinically . ImagingFistulae in the pelvis may be classified by the two structures involved and include genitourinary, intestinogenitourinary and genitocutaneous fistulas. Genitourinary fistulas include vesicouterine, vesicovaginal, urethrovaginal, and ureterovaginal fistulas. Intestinogenitourinary fistulas include colouterine, colovaginal, colovesical, and rectovaginal fistulas. A variety of cutaneous fistulas may form in the pelvis, including genitocutaneous fistulas such as perineovaginal. Additionally, some patients may have a compound or mixed fistulae, involving more than two pelvic organs , 3.Clinical presentation varies by the structures that have fistulized. Genitourinary fistulas may cause incontinence, vaginal urine leakage, localized pain, vaginal pruritis, perineal skin irritation, and recurrent infections of the genitourinary tract. Colovesical and enterovesical fistulas typically produce gas or fecal material in the urine. Changes in vaginal discharge, recurrent vaginal infection or abnormal passage of stool, mucus or flatus per the vagina suggests the presence of a rectouterine, rectovaginal, or colovaginal fistula , 4. SmalRadiologic evaluation of fistulas is paramount in their diagnosis. In some cases, imaging may provide direct visualization of a fistulous tract. In other cases, imaging may demonstrate focal wall thickening, the presence of air or contrast material in a non-anatomic location, or loss of a normal soft tissue plane .Radiologic diagnosis can be complemented by physical and laboratory examinations. In addition to a thorough physical exam, a variety of diagnostic tests can help identify the presence of a fistula. Vaginal fluid analysis can be performed to test for urea, creatinine, and potassium, which would suggest a genitourinary fistula. In a pyridium test, a tampon placed in the vagina is examined for staining after the administration of oral phenazopyridine. If positive, this suggests the presence of a ureterovaginal fistula. This can be performed in tandem with a methylene blue test, where methylene blue is instilled retrograde into the bladder and a tampon in the vagina is examined for the presence of blue dye, indicating a vesicovaginal fistula. When done concurrently, this is referred to as the double-dye test. Cystoscopy should also be performed for direct visualization of genitourinary fistulas . A specuFluoroscopic evaluation via cystogram, excretory urography, vaginography, water-soluble enemas and fistulograms can be used to evaluate pelvic fistulas. Fluoroscopy is widely accessible and cost-effective. Additionally, real-time imaging on fluoroscopy can be advantageous as the radiologist can utilize different projections and provocative maneuvers to visualize a fistula. Oblique and lateral views can be particularly helpful. However, fluoroscopy alone is somewhat limited in that the radiologist has limited visualization of associated complications, and there is little anatomic detail.Similar to fluoroscopy, computed tomography (CT) is also broadly available and cost-effective. CT also offers increased sensitivity and accuracy for the detection of fistulas compared with fluoroscopy. Multiphasic acquisition  are essential. Even if a fistula is difficult to directly visualize, there may be indirect signs such as gas or contrast in the bladder . AdditioMRI is the examination of choice for evaluating pelvic fistulas due to its high intrinsic soft tissue contrast, which allows for direct visualization of the tract , 5–7. MuRadiographs and ultrasound offer little diagnostic value in the setting of pelvic fistulae. Radiographs are quick and may be helpful to easily visualize presence of intraperitoneal or intravesical air. Endoanal ultrasound can be used in a conjunction with MRI to evaluate the anal sphincter in anovaginal fistulae . OtherwiFistulas have numerous causes including malignancy, birth trauma and gynecologic pathologies as well as infectious, inflammatory and iatrogenic etiologies .Genitourinary tract fistulae include any fistula between the female genital tract and the bladder, urethra, or ureters, with vesicovaginal fistulas being the most common. Worldwide, obstetric trauma is the most common cause of genitourinary fistula formation. Pressure necrosis in the setting of obstructed labor often causes large fistulae. In low- and middle-income countries in the Middle East, Africa and Asia, incidence of birth-related fistulas is estimated at one to three out of 1000 deliveries .Postsurgical causes of pelvic fistulae are more common in developed countries. Postoperative genitourinary fistula typically occurs as an early complication (less than 30 days post-operative) after gynecologic surgery . FistulaNeoplasm involving any of the pelvic organs  can cause fistula from direct tumor invasion. Approximately 2.5% of patients with gynecologic malignancy develop fistulas, with vesicovaginal and colovaginal being most common .Post-radiation therapy fistula formation can be caused by tumor downsizing or fibrosis and tissue necrosis. Fibrosis is a later complication, occurring 1–2 years after treatment after external beam radiation or brachytherapy of the vaginal vault or prostate. Radiation-induced fibrosis and loss of normal anatomy and soft tissue planes causes endarteritis obliterans and ischemic necrosis, allowing fistula formation , 12, 13.Any inflammatory or infectious process in the pelvis may predispose to fistula formation. Intrapelvic foreign body erosion can result in genitourinary fistula, such as erosion of a pelvic mesh into the urethra as illustrated in Fig. Inflammatory processes, in particular diverticular disease and inflammatory bowel disease, commonly cause intestinogenitourinary fistulas. Fistula formation has been reported at a rate up to 14% following acute diverticulitis . ColovesThe pathophysiology of fistula formation in Crohn’s disease is not well understood; however, theories include mucosal and transmural inflammation and luminal bacteria . In CrohSimilar to genitourinary tract fistulae, anovaginal and rectovaginal fistulas are most commonly caused by obstetric trauma due to pressure necrosis from prolonged labor. Infections, particularly from chronic granulomatous disease such as tuberculosis, schistosomiasis, and actinomycosis, as well as retained foreign bodies are also associated with intestinogenitourinary fistula formation.Finally, intestinogenitourinary fistulas can result from pelvic malignancy, either by direct tumor invasion, due to post-radiation therapy, or as a postsurgical complication. Figure Occasionally, multiple pelvic fistulas may be present simultaneously. Multiple complex fistulas often occur in the setting of prior surgery due to postsurgical changes and active inflammatory processes. An example of multiple complex fistulas is demonstrated in Fig. Pelvic fistulas are often difficult to treat, and a multidisciplinary approach with surgery, urology, gynecology, and gastroenterology is frequently necessary for appropriate management .Conservative management of pelvic fistulas may be appropriate if the fistulous tract is simple, small, and unrelated to malignancy or radiation therapy. Treatment typically involves antibiotic therapy and abscess drainage if present. For fistulas involving the urinary tract, urinary diversion with transurethral catheters, suprapubic catheters or nephrostomy may allow a tract to heal , 21. SitThe majority of pelvic fistulas require operative management and depends on location, etiology, fistula morphology, and history of prior repair. The edges of a fistula may be surgically debrided or the tract may be excised and closed with sutures . Grafts Pelvic fistula is a devastating condition that causes significant morbidity and evaluation can be challenging. Imaging, and particularly MRI, plays a vital role in the diagnosis, characterizing the course of a fistula and demonstrating associated complications, which are essential to guide treatment decisions. A multidisciplinary approach is often necessary for adequate treatment.


Fibroblastic connective tissue nevus (FCTN) is a rare, benign, and recently described dermal mesenchymal lesion characterized by CD34-positive spindle cells. We present a case of FCTN on the upper back of a 9-month-old boy who was diagnosed with a benign lipoma by ultrasound. Fibroblastic connective tissue nevus (FCTN) is a rare, cutaneous mesenchymal lesion initially described by de Feraudy and Fletcher in 2012 [A healthy 9-month-old male presented with an asymptomatic, well-defined, nonmobile subcutaneous nodule of the upper back. The lesion appeared in the first two months of life and slowly increased in size. The ultrasound showed a 4-cm long heterogenous lesion with a solid appearance and an echogenicity similar to that of fat. There was no connection with the deep fascia. The ultrasound diagnosis was compatible with a lipoma and was surgically removed as the lesion had grown in the last month. Since clinically and ultrasonographically the diagnosis was unclear, it was preferential to remove it.Histopathological examination revealed a papillomatous epidermis without atypia. In the deep reticular dermis and superficial subcutis, a poorly circumscribed lesion consisting of bundles of monomorphic spindle cells with pale eosinophilic cytoplasm arranged in a disorderly manner in the short fascicle in the stroma, was observed. Furthermore, entrapped adnexal structures with abundant mature adipocytic components were also found. Atypical mitoses, cytologic atypia, or other features suggestive of malignant transformation were absent. Immunohistochemistry revealed that the cells were CD34-positive, while they were negative for smooth muscle actin, S100, desmin, myoglobin, Factor XIIIa, and CD31 . MoreoveFibroblastic connective tissue nevus is an infrequent, benign, cutaneous mesenchymal lesion of fibroblastic and myofibroblastic origin, first described by de Feraudy and Fletcher . The cliMicroscopically, the lesion shows a poorly circumscribed, deep dermal proliferation of fibroblastic cells arranged in disordered short fascicles entrapping collagen bundles and sweat glands without destruction of the structures. There is no evidence of cytological atypia, mitosis, or necrosis. Immunohistochemically, these cells are CD34-positive in 87% of cases, smooth muscle actin-positive in less than 50% of the cases, but S100-negative in all cases, which is consistent with a fibroblastic/myofibroblastic process [The differential diagnosis is broad and includes dermatofibroma, dermatomyofibroma, plaque-stage dermatofibrosarcoma protuberans (DFSP), CD34-positive plaque-like dermal fibroma, fibroblastic-predominant plexiform fibrohistiocytic tumor, and fibrous hamartoma of infancy, among others ,3,4,5,6.One of the most important differential diagnoses includes DFSP  which maIn summary, we report a case of an infrequent fibroblastic connective tissue nevus with an ultrasonographic appearance of a lipoma. The histological and immunohistochemical features support our diagnosis of FCTN. This lesion is benign, and patients have a good prognosis with local excision.


Ectopic adrenocorticotropic syndrome (EAS) is a rare cause of endogenous ACTH-dependent Cushing’s syndrome, usually associated with severe hypercortisolism as well as comorbidities. Tumor detection is still a challenge and often requires several imaging procedures. In this report, we describe a case of an ectopic ACTH secretion with a misleading localization of the responsible tumor due to a concomitant rectal carcinoma.68Ga]-DOTA-TOC PET/CT scan was negative, while [18F]-FDG-PET/CT showed a tracer accumulation in the superior nodule. After a multidisciplinary consultation, the patient underwent thoracic surgery that started with two atypical wedge resections of nodules. Frozen section analyses showed a neuroendocrine tumor on the right middle lobe nodule and a metastatic colorectal adenocarcinoma on the superior lesion. Then, a right superior nodulectomy and a right middle lobectomy with mediastinal lymphadenectomy were performed. The final histopathological examination confirmed a typical carcinoid tumor, strongly positive for ACTH. A post-surgical follow-up showed a persistent remission of Cushing’s syndrome.A 49-year-old man was referred to our Endocrinology Unit due to suspicion of Cushing’s syndrome. His medical history included metastatic rectal adenocarcinoma, diagnosed 5 years ago and treated with adjuvant chemotherapy, radiotherapy and surgical resection. During follow-up, a thoracic computed tomography scan revealed two pulmonary nodules located in the superior and middle lobes of the right lung with a diameter of 5 and 10 mm, respectively. However, these nodules remained radiologically stable thereafter and were not considered relevant. All biochemical tests were suggestive of EAS  and radiological localization of the ectopic ACTH-secreting tumor was scheduled. The CT scan revealed a dimensional increase of the right superior lung nodule (from 5 to 12 mm). [The present report describes a case of severe hypercortisolism due to EAS not detected by functional imaging methods, in which the localization of ACTH ectopic origin was puzzled by a concomitant metastatic rectal carcinoma. The multidisciplinary approach was crucial for the management of this rare disease. Cushing’s syndrome (CS) is caused by a chronic exposure to supraphysiological levels of glucocorticoids leading to several comorbidities and high mortality if not adequately treated . An ectoHere we describe the case of a severe CS due to ectopic ACTH secretion with a misleading localization of the responsible tumor due to a concomitant rectal carcinoma.18F]-FDG) uptake at positron emission tomography (PET) performed in September 2017, they were not considered relevant.A 49-year-old Caucasian man was referred to our Endocrinology Unit in June 2020 from the Hepatology Unit with suspicion of CS. The patient reported a recent occurrence of severe backache and progressive muscular weakness, leading to gait impairment and the need to use crutches. His past medical history was relevant for a left knee chondroblastoma, diagnosed and surgically treated at 14 years of age, and a rectal adenocarcinoma with liver metastasis, diagnosed in 2015 and treated with adjuvant chemotherapy, radiotherapy and surgical resection. Thereafter the patient underwent a regular oncologic follow-up and in June 2017, a thoracic computed tomography (CT) scan revealed two pulmonary nodules located in the superior and middle lobes of the right lung with a diameter of 5 and 10 mm, respectively. However, since these two nodules remained stable during radiological follow-up, including CT scans in 2018 and 2019, and did not show fluorodeoxyglucose  with central adiposity, a moon face and a buffalo hump. The patient also presented proximal miopathy and scattered bruises, while no striae rubrae was present. The blood pressure was at 170/120 mmHg and the fasting capillary glycemia was at 310 mg/dl. The other biochemical features are summarized in Physical examination showed the patient being overweight (BMI: 26.6 kg/m68Ga]-DOTA-TOC PET/CT scan did not show any pathologic tracer accumulation. On a [18F]-FDG-PET/CT (capillary glycemia <150 mg/dl before examination), the right superior nodule took-up the radiopharmaceutical with a maximum standardized uptake value (SUV) of 2.4, while the other pulmonary nodule did not accumulate [18F]-FDG (The diagnostic work-up included four major steps: 1) Biochemical confirmation of CS; 2) Classification as ACTH-dependent CS; 3) Differential diagnosis between Cushing’s Disease (CD) and EAS; and 4) Localization of ACTH-secreting tumor and evaluation of its extension. The biochemical diagnosis was rapidly posed as all the tests were suggestive of EAS Table 1 The assessment of the CS-associated comorbidities revealed multiple vertebral and costal fractures, the former accounting for the patient’s back pain; rapidly worsening glucose control, which required basal-bolus insulin therapy; severe hypokalemia and refractory hypertension which needed a progressive increase of canrenone of up to 300 mg/day in addition to three other antihypertensive drugs Table 2.Immediately after the laboratory and radiological assessment, medical therapy with metyrapone, a steroidogenesis enzyme inhibitor, was started. Due to severe and refractory hypokalemia and hypertension, the initial dose was at 500 mg/day, which quickly increased to 1,000 mg/day. This dose allowed a rapid and important reduction of basal cortisol levels and a normalization of free urinary cortisol Figure 1In the meantime, the case was discussed in a multidisciplinary team that included an endocrinologist, a thoracic surgeon, an anaesthesiologist, a neurosurgeon, and a radiologist. After that, it was decided to refer the patient to a thoracic surgery with the aim to analyze the pulmonary nodules through frozen section and then proceed with thoracic surgery, according to the results. The patient was informed by the multidisciplinary team on the procedure and its associated risks, including the possible need for a chronic oxygen therapy because of his low pulmonary function. The patient accepted the surgery and pulmonary rehabilitation, in addition to continuous-positive airway pressure (CPAP) therapy, which was immediately started. One week later, the patient underwent a minimally invasive thoracic surgery. Surgical procedure started with two atypical wedge resections of nodules. Frozen section analyses resulted positive for neuroendocrine tumor on right middle lobe nodule and for metastatic colorectal adenocarcinoma on the superior lesion. For oncological reasons a right middle lobectomy and a mediastinal lymphadenectomy were performed. The postoperative course was uneventful and the patient was discharged on post-operative day 4 in good clinical condition. The final histopathological examination confirmed the frozen section procedure results: a colorectal carcinoma metastasis in the right superior pulmonary nodule and a typical carcinoid tumor (according to the WHO 2015 classification), strongly positive for ACTH immunostaining, in the middle lobe Figure 2“I remember my first endocrinological visit at Fondazione Ca’ Granda, Ospedale Maggiore Policlinico, I was feeling tired, very anxious, also depressed, with mood swings and I was having difficulties to concentrate. My back was aching very hard and I was able to walk only a few steps with two crutches and my face was swollen and reddish. My symptoms began three four months before and worsened quickly. The weeks after the surgical procedure I was feeling very tired, my appetite lacked, but my mind was clear and I was feeling more optimist. After three months my back still hurts, but less than before and I can easily walk with one crutch, so now I’m autonomous. My appetite is normal, I feel energetic, my mind is clear and I have begun to do small jobs. Overall, I can say that my quality of life significantly improved after the surgical intervention.”The present case report describes an unusual association of a lung carcinoid tumor responsible for a severe EAS with a metastatic rectal cancer that puzzled the localization of ectopic ACTH source. Although the state of intense hypercortisolism is not precisely defined in the literature, it was seen that the CS complications are more frequent and rapidly evolving when UFC is increased five times above the upper limit of normal range (ULN) . In thes68Ga]-DOTA-TOC PET/CT scan, that resulted negative, and a [18F]-FDG-PET/CT scan that showed a radiopharmaceutical uptake of the nodule located in the superior lobe of right lung. The second nodule was not reported as [18F]-FDG avid, although the small size lowered the sensitivity of the examination. The performance of [68Ga]-DOTA-TOC PET/CT and [18F]-FDG-PET/CT for the detection of EAT is still debated. [68Ga]-DOTA-TOC PET/CT is usually preferred in occult tumors, that are often non-metastatic and well-differentiated NETs. In fact, the slow growth rate of these tumors can determine a negative result to [18F]-FDG-PET/CT  , 13 and G-PET/CT , which iG-PET/CT .68Ga]-DOTATOC PET/CT provides a high sensitivity (88–93%) and specificity (88–95%) for the diagnosis of carcinoid tumor ?; ii. EAT of right middle lobe with false negative [As stated before, an indication to thoracic surgery was confirmed after a multidisciplinary discussion and motivated by the following arguments: first, the patient suffered from a severe and life-threatening form of CS; second, metyrapone therapy is able to inhibit adrenal steroidogenesis but it does not target the primary cause of cortisol excess and may have various side effects such as hypertension, hypokalaemia, and adrenal insufficiency ; and thiThe frozen section examination revealed an EAT in the middle lobe of the right lung and a rectal carcinoma metastasis in the right superior lobe. An atypical resection of the right superior pulmonary lobe for the rectal metastasis and a middle lobectomy lymphadenectomy for the ACTH positive carcinoid tumor were performed accordingly. Then, in the present case the pulmonary carcinoid tumor was not detected in either functional imaging methods.In conclusion, the present report describes a case of severe hypercortisolism due to EAS in which the localization of ACTH ectopic origin was puzzled by a concomitant metastatic rectal carcinoma. The biochemical diagnosis of EAS was instrumental in the reassessment of apparently benign lung nodules and the past history of metastatic rectal cancer imposed a rapid surgical exploration of both lesions. A multidisciplinary approach as well as a clear and close communication with the patient played a crucial role in the management of this case.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.AS, GM, EF, MA, MR, MC, and ACh: diagnostic approach of the case and writing the paper. AS and GC: editing images. ACr, RI, and BM: sample collection and preparation and patient follow-up. LR, PM, and MN: surgical treatment of the patient and writing the paper. GC: histopathological examination. All authors contributed to the article and approved the submitted version.This work was supported by Ricerca Corrente Funds from the Italian Ministry of Health.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.