Small cell neuroendocrine carcinoma of the uterine cervix presenting with syndrome of inappropriate antidiuretic hormone secretion
A 41-year-old Korean woman with parity of 3-0-4-3 who had no significant findings in a Pap smear conducted 9 months earlier than she came to the hospital. She had suffered vaginal spotting and blood tinged vaginal discharge for 5 months and experienced vaginal bleeding the day before she went to see a doctor in February 2012.\nPhysical examination revealed no abnormal findings, and gynecological examination showed exocervical protruded cervical mass measured about 4.5 cm in diameter and parametrium was not involved. Colposcopy confirmed the polypoid mass arising from the exocervical side of the cervix. Biopsy of this tumor was reported histologically as small cell carcinoma of the cervix. On T2-weighted imaging of pelvic magnetic resonance imaging (MRI), an enhancing tumor of the uterine cervix, sized 3.5×3.6×4.7 cm, was found and normal cervical stromal hyposignal intensity was almost missing (). Irregular spiculated margin of the tumor mass was noted. Vaginal invasion was not observed but two prominent lymph nodes were noted along the both iliac chains (). Chest X-ray did not show any significant findings. Since the tumor was over 4 cm in size and limited to the cervix without findings of vaginal or parametrial invasion, we clinically diagnosed her illness as cervical cancer IB2.\nHer blood test showed the following results: hemoglobin 12.1 g/dL, white blood cell 6,000/µL, and platelet 359,000/µL. Liver function tests, renal function tests and coagulation profile were all normal while urinalysis was normal except hematuria, and urine specific gravity was 1.015. She was positive for high-risk human papillomavirus (HPV) 18, and carcinoembryonic antigen (CEA) was 3.81 ng/mL higher than normal levels (under 3 ng/mL), and the level of squamous cell carcinoma antigen was 1.14 ng/mL (normal range, 0-2 ng/mL). There were no abnormal findings from an esophagogastroscopy, colonoscopy and cystoscopy. Before surgery, we found the hyponatremia ,124 mEq/L (normal range, 135-145 mEq/L) and low chloride 97 mEq/L (normal range, 98-110 mEq/L), although the serum potassium concentration was normal, 4.5 mEq/L (normal range, 3.5-5.5 mEq/L). After the administration of intravenous hydration, the levels of sodium and chloride dropped even further to 122 mEq/L and 91 mEq/L, respectively. The diagnosis of SIADH was confirmed by diagnostic criteria, i.e., decreased serum osmolality (252 mOsm/kg) and elevated urine osmolality (384 mOsm/kg). There were no significant findings from thyroid function tests and adrenal functions were normal. Under the diagnosis of SIADH, we treated her with water restriction and 3% hypertonic saline. Her blood sodium and chloride levels return to normal (136 mEq/L and 105 mEq/L, respectively), and proceeded with surgery. The types of surgical procedures were a radical hysterectomy, bilateral salpingectomy, pelvic lymph node dissection and para-aortic lymph node dissection.\nDuring operation, the size of uterus was normal and exocervical mass measured about 4.5 cm in size was found. Grossly, invasion into parametrium, paracolpium or vagina was not found. Both adnexa were normal, but we found both external iliac lymph nodes slightly swollen. Microscopic findings showed that tumor cells were small and round- or spindle-shaped with hyperchromatic nuclei and scant cytoplasm (). Tumor size was 4 × 3.5 × 3.5 cm and subtle parametrial invasion was present, but the depth was less than 0.1 cm (). We observed myometrial invasion () and metastases to both external iliac lymph nodes () as well. The immunocytochemical profile demonstrated marker positivity for neurone-specific enolase and positive for chromogranin (). They were partially positive for cytokeratin and negative for leukocyte common antigen, so we diagnosed her with small cell carcinoma.\nOn 48 hours after surgery, the serum sodium were increased and showed persistent normal range (over 135 mEq/L). Potassium and chloride were also normal (3.8 mEq/L and 106 mEq/L).\nShe was discharged 11days after surgery without any significant complications. Considering the high risk factors of the pathology, the patient received concurrent chemoradiotherapy (CCRT) on 30 days after operation. There is no definite abnormal finding on follow-up pelvic computed tomography (CT) taken 3 months after the operation. However, 4 months after surgery, the patient was admitted to our hospital because of anorexia and fatigue. She had hyponatremia (133 mEq/L) and elevated CRP (c-reactive protein) (7.88 mg/dL; normal, 0-0.3 mg/dL). On abdominal and pelvic CT scanning showed multiple enlarged para-aortic lymph nodes. These data strongly suggested the recurrence of small cell cervical carcinoma. with SIADH. After the completion of carboplatin-paclitaxel chemotherapy (×3 cycles), positron emission tomography (PET)-CT scanning conducted.\nBut, metastases to Lt (left) common iliac chain, retrocaval and Lt para-aortic areas were existed. Those enlarged lymph nodes were removed at 8 months after the first surgery. CEA, a tumor marker of this case, had been within a normal range after the first surgery but rose to 4.92 ng/mL before removal of recurrent lymph nodes. But after the lymph node excision, CEA level returned to normal again (1.62 ng/mL). However, after 1year, the first surgery which means 4 months after the lymph node excision, the CEA level has been elevated up to 4.41 ng/mL and PET-CT results showed that there is metastasis of para-aortic lymph nodes, supraclavicular lymph nodes and right femur lymph nodes. Therefore the patient underwent radiation therapy and now is having etoposide-cisplatin chemotherapy.