Ulcerated<unk>  affecting the skin of the nose in an elderly individual To diagnose<unk> s, a skin biopsy is performed for histopathologic analyses. The most common method is a shave biopsy under local anesthesia. Most nodular<unk> -cell cancers can be diagnosed clinically; however, other variants can be very difficult to distinguish from benign lesions such as intradermal naevus, sebaceomas, fibrous papules, early acne scars, and hypertrophic scarring. Exfoliative cytology methods have high sensitivity and specificity for confirming the diagnosis of<unk>  when clinical suspicion is high but unclear usefulness otherwise. Characteristics High-magnification micrograph of<unk> .<unk> <unk> s appear similar to epidermal<unk> <unk> s, and are usually well differentiated. In uncertain cases, immunohistochemistry using BerEP4 can be used, having a high sensitivity and specificity in detecting only<unk> <unk> s. Main classes<unk>  can broadly be divided into three groups, based on the growth patterns. # Superficial<unk> , formerly referred to in-situ<unk> , is characterized by a superficial proliferation of neoplastic<unk> -cells. This tumor is generally responsive to topic chemotherapy, such as imiquimod, or fluorouracil, although surgical treatment is better able to ensure complete removal and confirm that there is not an underlying more aggressive subtype that was not sampled in the initial biopsy. # Infiltrative<unk> , which also encompasses morpheaform and micronodular<unk> -cell cancer, is more difficult to treat with conservative methods, given its tendency to penetrate into deeper layers of the skin. # Nodular<unk>  includes most of the remaining categories of<unk> -cell cancer. It is not unusual to encounter heterogeneous morphologic features within the same tumor. Nodular<unk> <unk>  with nodular pattern. Nodular<unk>  (also known as "classic<unk> ") accounts for 50% of all<unk> . It most commonly occurs on the sun-exposed areas of the head and neck. Histopathology shows aggregates of<unk> oid<unk> s with well-defined borders, showing a peripheral palisading of<unk> s and one or more typical clefts. Such clefts are caused by shrinkage of mucin during tissue fixation and staining. Central necrosis with eosinophilic, granular features may be also present, as well as mucin. The heavy aggregates of mucin determine a cystic structure. Calcification may be also present, especially in long-standing lesions. Mitotic activity is usually not so evident, but a high mitotic rate may be present in more aggressive lesions. Adenoidal<unk>  can be classified as a variant of NBCC, characterized by<unk> oid<unk> s with a reticulated configuration extending into the dermis. File:Palisading in<unk> <unk>  cancer.Palisading File:Nodular<unk> <unk>  cancer with cleft.Cleft. Other subtypes Other more specific subtypes of<unk>  include: Type Histopathology Other characteristics Image Cystic<unk>  Morphologically characterized by dome-shaped, blue-gray cystic nodules. 150px Morpheaform<unk>  (also known as "cicatricial<unk> ", and "morphoeic<unk> ") Narrow strands and nests of<unk> oid<unk> s, surrounded by dense sclerotic stroma. Aggressive 150px Infiltrative<unk>  Deep infiltration. Aggressive Micronodular<unk>  Small and closely spaced nests. 150px Superficial<unk>  (also known as "superficial multicentric<unk> ") Occurs most commonly on the trunk and appears as an erythematous patch. 150px Pigmented<unk>  exhibits increased melanization. About 80% of all<unk>  in Chinese are pigmented while this subtype is uncommon in white people. Rodent ulcer (also known as a "Jacob's ulcer") Nodular, with central necrosis. Generally a large skin lesion with central necrosis. Fibroepithelioma of Pinkus Anastomosing epithelial strands in a fenestrated pattern Most commonly occurs on the lower back. 150px Polypoid<unk>  Exophytic nodules (polyp-like structures) Generally on head and neck. Pore-like<unk>  Resembles an enlarged pore or stellate pit. Aberrant<unk>  Absence of any apparent carcinogenic factor, and occurring in odd sites such as the scrotum, vulva, perineum, nipple, and axilla. Aggressiveness patterns There are mainly three patterns of aggressiveness, based mainly the cohesion of cancer<unk> s: Low-level aggressive pattern Moderately aggressive pattern Highly aggressive pattern File:Low-level aggressive<unk> .Cohesive nodular File:Micrograph of superficial<unk> .Superficial File:Micrograph of<unk>  with fibroepitheliomatous pattern.Fibroepitheliomatous pattern (anastomosing<unk> oid epithelial strands enclosing round islands of fibrous stroma) File:Moderately aggressive<unk> .Moderate cohesion File:Morpheaform<unk> .Narrow strands and nests of<unk> oid<unk> s. "Cicatricial" or "morphoeic" pattern. Differential diagnoses +Main histological differential diagnoses of<unk> : Differential diagnosis Pathological Features Image Hair follicles Peripheral sections may look like nests, but do not display atypia, nuclei are smaller, and serial sections will reveal the rest of the hair follicle. 190px Squamous-cell<unk>  of the skin Squamous-cell<unk>  of the skin is generally distinguishable by for example relatively more cytoplasm, horn cyst formation and absence of palisading and cleft formations. Yet, a high prevalence means a relatively high incidence of borderline cases, such as<unk>  with squamous<unk>  metaplasia (H&E stain at left in image). BerEP4 staining helps in such cases, staining only<unk> <unk> s (right in image). 190px Trichoblastoma Absence of cleft, rudimentary hair germs, papillary mesenchymal bodies. 190px Adenoid cystic<unk>  Lack of<unk> oid<unk> s disposed in peripheral palisades; adenoid-cystic lesion without connection to the epidermis; absence of artefactual clefts 190px Microcystic adnexal<unk>  Bland keratinocytes, keratin cysts, ductal differentiation. BerEp4- (in 60% of cases), CEA+, EMA+ File:Micrograph of microcystic adnexal<unk>  - superficial follicular keratin-filled cysts.jpg File:Micrograph of microcystic adnexal<unk>  - infiltrative aggregates.jpg Trichoepithelioma Rims of collagen bundles, calcification, follicular/sebaceous/infundibular differentiation and cut artefacts. Cytokeratin (CK)20+, p75+, Pleckstrin homology-like domain family A member 1 + (PHLDA1+), common acute lymphoblastic leukemiaantigen + (CD10+) in tumor stroma, CK 6-, Ki-67- and Androgen Rceptor- (AR-) 190px Merkel<unk><unk> <unk> s arranged in a diffuse, trabecular and/or nested pattern, involving also the subcutis. Mouse Anti-Cytokeratin (CAM) 5.2+, CK20+, S100-, human leukocyte common antigen- ( LCA-), thyroid transcription factor 1- (TTF1-) 190px Radicality Comparison H&E stain (left) with BerEP4 immunohistochemistry staining (right) on a pathological section having<unk>  with squamous<unk>  metaplasia. Only<unk> <unk> s are stained with BerEP4. In suspected but uncertain<unk> <unk> s close to the resection margins, immunohistochemistry with BerEp4 can highlight the<unk> <unk> s.
Basal-cell carcinoma
Melanoma
Lymphoepithelioma
Seborrheic keratosis
Trichoepithelioma
Psoriasis
Angiokeratoma
Milium (dermatology)