Giant clear cell hidradenoma of the knee

Hidradenomas, also referred to as nodular hidradenomas or clear cell hidradenomas (CCH), are benign cutaneous eccrine tumors usually 2–3 cm in dimension. Hidradenomas are relatively common; however, giant forms are rare. We report a case of an 8.0 × 6.0 × 3.0 cm clear cell hidradenoma of the left knee in a 43‐year‐old man. The tumor was mobile, located above the patellar tendon and was without bony involvement on imaging studies. Grossly, the resected tumor was unencapsulated and tan, with a solid and cystic cut surface showing papillary excrescences on the cyst wall. Microscopically, the tumor cells showed an infiltrative growth pattern at the periphery, however, the tumor cytology was bland and no necrosis or mitoses were identified. The overlying dermis contained hemosiderin pigment deposition and infiltration with eosinophils. Immunohistochemically, tumor cells were positive for cytokeratin, CAM5.2, p53, carcino‐embryonic antigen (CEA) and epithelial membrane antigen (EMA), and negative for CD10 and Ki‐67. The cytological features of hidradenomas can present diagnostic challenges, as other ‘clear cell’ tumors such as metastatic renal cell carcinoma should be considered. Immunohistochemical studies and differential diagnoses are discussed. Yu G, Goodloe S, D’Angelis CA, McGrath BE, Chen F. Giant clear cell hidradenoma of the knee.     

A rare case of cutaneous oncocytic hidradenoma

Oncocytes are epithelial cells characterized by their abundant eosinophilic and finely granular cytoplasm. Their histologic appearance is due to excessive amounts of cytoplasmic mitochondria. Oncocytes generally occur in the setting of benign neoplasms. Oncocytomas, or tumors composed primarily of oncocytes, are typically found in the kidneys. Other common sites include the salivary, thyroid, and parathyroid glands. Oncocytic metaplasia has only been rarely reported in various cutaneous neoplasms. We report a case of an elderly male presenting with a 5 mm erythematous papule on his left scalp, who underwent a shave biopsy showing a nodular, dermal‐based adnexal tumor with prominent ductal differentiation, composed of multiple small, well‐formed lumina surrounded by enlarged and bland‐appearing epithelioid cells. Cytokeratin 7 (CK7), epithelial membrane antigen (EMA) and monoclonal carcinoembryonic antigen (mCEA) immunohistochemical stains were positive, consistent with adnexal differentiation. Phosphotungstic acid‐hematoxylin (PTAH) and Luxol fast blue (LFB) stains highlighted the cytoplasmic granules, consistent with mitochondria. The overall findings were consistent with an oncocytic nodular hidradenoma. Oncocytic hidradenoma is a very rare entity, with only 1 previously reported case in the literature.     

EMA positivity in epithelioid fibrous histiocytoma: a potential diagnostic pitfall

Background: Epithelioid fibrous histiocytoma (EFH) represents a morphologic variant of cutaneous fibrous histiocytoma (FH) but can lack many characteristic features. The presence of epithelioid cytomorphology may mimic other dermal neoplasms. Our anecdotal experience of epithelial membrane antigen (EMA) expression in some examples of EFH has caused diagnostic difficulty. Our aim was to examine the immunohistochemical profile and incidence of EMA expression in EFH. Methods: Forty‐four cases of EFH were retrieved from consultation files. Clinicopathologic and immunohistochemical features were evaluated. Results: Membranous EMA positivity was found in tumor cells in 27/42 cases (64%). Focal positivity for factor XIIIa was found in 10/14 (71%) and D2‐40 in 14/27 (52%). Scattered smooth muscle actin (SMA)‐positive tumor cells were seen in 11/43 (25%). Focal positivity for claudin‐1 was found in 3/42 (7%). CD163 staining highlighted stromal macrophages; however, in five cases it was difficult to exclude focal staining of tumor cells. Tumor cells were consistently negative for pan‐keratin, AE1/AE3, S100, CD31, CD34, CD68, desmin, p63, GFAP and CD45/LCA. Conclusion: Frequent EMA expression in EFH represents an unexpected finding and constitutes a potential diagnostic pitfall. Although of uncertain significance, this finding, when combined with established morphologic differences, raises the possibility that EFH is unrelated to classic FH. Doyle LA, Fletcher CDM. EMA positivity in epithelioid fibrous histiocytoma: a potential diagnostic pitfall.     

Cutaneous malignant mixed tumor. Report of a case and review of the literature

We describe an unusual malignant cutaneous neoplasm having a biphasic growth pattern and apparently arising in a mixed tumor. A lymph node metastasis was similar histologically to the primary lesion, exhibiting both carcinomatous differentiation and areas that appeared sarcomatous. Immunohistochemical stains showed selective staining for high molecular weight keratin in carcinomatous areas and for vimentin in areas having a sarcomatous appearance. The literature of cutaneous malignant mixed tumor is reviewed and possible explanations for the unusual morphology and immunohistochemical staining pattern are discussed.     

Clear cell hidradenoma: a tumor with basaliomatous changes in the overlying epidermis and follicular infundibula of surrounding skin.

We report a clear cell hidradenoma on the cheek of a Japanese man. We performed the primary operation on the flesh-colored tumor, which had surface telangiectasia. The histopathologic features of the tumor, which indicated an intradermal nodular hidradenoma, consisted mainly of typical clear cells with small numbers of eosinophilic fusiform cells. Most clear cells reacted negatively for CEA, EMA, S-100 protein and KL-1 keratin, but those in and around the cystic and ductal structures reacted positively for CEA, EMA and KL-1 keratin. Ultrastructurally, these clear cells had numerous microvillus processes, abundant intracytoplasmic glycogen granules, and numerous mitochondria. In addition, buds of hyperpigmented keratinocytes hung from the overlying epidermis and thin cords of hyperpigmented keratinocytes proliferated around the follicular infundibula beside the tumor. Within two months of the primary operation, growth of the tumor into the overlying epidermis recurred rapidly. We discuss the histological features of the combination of clear cell hidradenoma with basaliomatous changes of the overlying and surrounding skin and the highly aggressive recurrence of this type of tumor after primary treatment.     

An Immunohistochemical Study of Sebaceous Carcinoma with Anti-Keratin Monoclonal Antibodies: Comparison with Other Skin Cancers

Formalin-fixed and paraffin-embedded tissue specimens of six cases of extraocular sebaceous carcinoma were studied immunohistochemically with eight anti-keratin monoclonal antibodies, 34βB4, 35βH11, Ks13.1, Ks19.1, PKK1, LP34, KL1 and AE1. The staining patterns of sebaceous carcinoma were compared with those of normal sebaceous glands and other skin cancers which should be distinguished from sebaceous carcinoma histopathologically. The other skin cancers compared were eccrine porocarcinoma, malignant clear cell hidradenoma, extramammary Paget's disease with underlying adenocarcinoma, malignant trichilemmoma, and squamous cell carcinoma. Most cases of sebaceous carcinoma were stained with 35βH11, Ks19.1, LP34, KL1 and AE1, while normal sebaceous glands were positive only with 35βH11, LP34, KL1 and AE1. By immunostaining, sebaceous carcinoma was distinguishable from extramammary Paget's disease with underlying adenocarcinoma, squamous cell carcinoma, malignant trichilemmoma, and eccrine porocarcinoma, but was not clearly distinguishable from malignant clear cell hidradenoma. These findings demonstrate that sebaceous carcinoma shows positive reactions with antibodies to simple epithelial keratin, probably as a result of neoplastic transformation, and that immunohistochemical examination using anti-keratin monoclonal antibodies is useful in distinguishing sebaceous carcinoma from several other skin cancers.     

Schwannoma with sweat duct differentiation

We report a schwannoma with well differentiated ducts resembling cutaneous sweat ducts. The tumor presented as a painless mass near the left knee of a 41-year-old female. The mass had been present for many years. Some increase in size had been noticed over the previous 2 to 3 yr. The bulk of the tumor was composed of spindle cells with the appearance of Antoni A and Antoni B tissue. Rare mitotic figures were noted. In several areas of the tumor, numerous well-differentiated ducts were present. Most resembled normal cutaneous sweat ducts. In some areas, cystic dilatation of the ducts was present. Focal areas demonstrated poorly formed ducts and single cells with prominent nuclei and ample cytoplasm. Well formed ducts, poorly formed ducts, and single cells marked with AE 1/3 (keratin) and epithelial membrane antigen. The spindle cell proliferation marked for S 100 protein and vimentin. Sweat duct differentiation has not been reported previously in either benign or malignant schwannoma. Light and electron microscopic features of this tumor are presented.     

Staining of melanocytic neoplasms by melanoma antigen recognized by T cells

We stained benign melanocytic nevi and malignant melanoma with antibodies to melanoma antigen recognized by T cells (Mart-1) to determine if this was useful in differentiating benign from malignant melanocytic neoplasms. Forty-five primary malignant melanomas and 71 benign melanocytic nevi were stained with antibodies to Mart-1. Two cases of malignant melanoma metastatic to lymph node and three cutaneous metastases of malignant melanoma were also stained. The degree of staining was graded into diffuse positive staining, focal positive staining, and negative staining. Thirty-six of 45 primary malignant melanomas stained diffusely positive with antibodies to Mart-1. This included three of five desmoplastic malignant melanomas that showed positive staining. Four melanomas showed faint or focal positive staining. One of two metastases to lymph node showed strong positive staining and one showed no staining. All three cutaneous metastases showed diffuse positive staining. Sixty-one of 71 melanocytic nevi showed no staining or faint staining with antibodies to Mart-1. Ten of 71 melanocytic nevi showed strong positive staining. The majority of these were congenital nevi. Staining with antibodies to Mart-1 antigen was a useful marker of malignant melanoma. However, staining may also be seen in benign melanocytic neoplasms. The presence or absence of staining for Mart-1 antigen cannot be used to differentiate benign melanocytic nevi from malignant melanocytic tumors.     

Squamomelanocytic tumor: a new case of a unique biphenotypic neoplasm of uncertain biological potential

Squamomelanocytic tumor is an uncommon cutaneous neoplasm composed of an admixture of melanocytic and squamous cellular phenotypes. We describe a case of this tumor in a 94-year-old man who presented with a nodule on the back. Histologically, a well-demarcated expansive dermal nodule was composed of anastomosing epithelial strands with focal formation of squamous pearls and ductal structures commixed with elongated spindle cells with clear cytoplasm grouped in nests. The two cell types were diffusely admixed or clustered in groups within the nodule. Immunohistochemical studies showed that the spindle cells grouped in nests expressed S-100 and HMB-45 antigens, and the squamoid cells expressed cytokeratins and carcinoembrionic antigen (CEA) protein only in the inner layer of the ducts and the cystic space. Atypical features and high mitotic activity was observed in the melanocytic cells but slight atypia, mild dyskeratosis and mitotic figures were observed also in the squamoid component. This tumor represents a proliferation of two phenotypic cells that are distinctive for their intimate admixture and singular immunohistochemical profile. The authors discuss the histogenesis of this tumor, suggesting that it could represent an atypical solid-cystic hidradenoma colonized by a melanocytic malignant component. The biological behavior of this neoplasm remains currently uncertain.     

Metastatic sarcomatoid renal cell carcinoma manifesting as a subcutaneous soft tissue mass

Metastases from visceral malignancies to subcutaneous soft tissues are relatively rare and their diagnosis requires a high level of suspicion. It is even more challenging if a metastatic lesion shows non‐specific high‐grade spindle cell morphology overlapping with various primary cutaneous and soft tissue tumors. We describe a unique case of subcutaneous metastasis of sarcomatoid renal cell carcinoma which was the first manifestation of the occult malignancy. The patient had a history of lipomas and dysplastic nevi and presented with an upper back mass. The mass, located superficially within the subcutis, was composed of atypical spindle cells arranged in a storiform pattern. By immunohistochemistry, the tumor cells were strongly diffusely positive for cytokeratin AE1/AE3 and vimentin and negative for Melan‐A, S‐100 protein, SOX10, melanoma cocktail, epithelial membrane antigen (EMA), p63, CK7, CK18, CK20, smooth muscle actin (SMA), desmin, CD34, TTF‐1, CD21, CD99 and bcl‐2. Scattered tumor cells were positive for MDM2 immunostain, but MDM2 amplification was not detected using fluorescent in situ hybridization (FISH). Co‐expression of cytokeratin and vimentin by the tumor raised the possibility of metastatic renal cell carcinoma and positivity of the tumor for PAX8 supported this hypothesis. A large renal mass was detected radiologically and the subsequent nephrectomy specimen showed high‐grade clear cell renal cell carcinoma with sarcomatoid features.     

Primary cutaneous mucoepidermoid carcinoma: report of a case

Primary mucoepidermoid carcinomas of the skin are extremely rare tumors. We describe a primary cutaneous mucoepidermoid carcinoma arising in the right ear (posterior mid helix) of a 66-year-old white man. The tumor was 0.6 cm in diameter, ulcerated and nonencapsulated. No other tumors were found in the patient. Histologically the tumor showed the characteristics of a "low grade" mucoepidermoid carcinoma, consisting of lobules of polygonal cells with vesicular nuclei. In the center of the lobules were large vacuolated cells (goblet cells). Transitions between the two cell populations were present throughout the tumor. An epidermal attachment of the tumor, as well as epidermal dysplasia, predominantly at the acrosyringium was present, consistent with the theory of sweat duct histogenesis of these tumors. Immunoperoxidase staining showed positivity for epithelial membrane antigen, keratin and carcinoembryonic antigen. The latter was predominantly positive in the goblet cells. Cutaneous metastasis of mucoepidermoid carcinomas with epidermal attachment has been reported. Our case showed only ear involvement and follow-up at 8 months has revealed no evidence of recurrence. These findings are consistent with the diagnosis of primary cutaneous mucoepidermoid carcinoma.     

Clear cell syringoid carcinoma: an ultrastructural and immunohistochemical study

Syringoid carcinoma (syringoid "eccrine" carcinoma or eccrine epithelioma) is a rare cutaneous tumor with some controversy regarding its correct definition. It may also be difficult to differentiate from its benign counterpart (syringoma), other adnexal carcinomas, and cutaneous metastasis from adenocarcinomas. We present a case of a syringoid carcinoma of the clear cell variant complemented with an immunohistochemical and ultrastructural study, the latter revealing cytoplasmic accumulation of glycogen and presence of intercellular and intracellular lumina in clear tumor cells, as well as diverse hallmarks of malignancy (i.e., perineural invasion, tumor necrosis, and deep invasion). Clear tumor cells showed cytoplasmic and membranous immunoreactivity to epithelial membrane antigen, carcinoembryonic antigen, keratins, and S-100. Our ultrastructural and immunohistochemical results support the ductal differentiation of the glycogen-filled clear cell tumor population.     

Combined sentinel lymphadenectomy and mohs micrographic surgery for high-risk cutaneous squamous cell carcinoma

BACKGROUND: There are subgroups of cutaneous squamous cell carcinoma (SCC) that have a higher risk for both regional and distant metastasis. When cutaneous SCC does metastasize, it typically spreads first to local nodal groups. Sentinel lymph node (SLN) localization has been successfully used to evaluate nodal metastasis in breast carcinoma, melanoma, and other select tumors. It may also be useful in certain high-risk cutaneous SCCs. Currently, Mohs micrographic surgery is the treatment of choice for these tumors. METHODS: A patient presented with a high-risk recurrent SCC on the forehead. The regional nodal groups were clinically negative and radiographically negative by computed tomographic scan. Sentinel lymphadenectomy was performed by means of technetium 99m-radiolabeled sulfur colloid. The main tumor was resected with Mohs micrographic surgery. RESULTS: A left preauricular SLN was localized by lymphoscintigraphy. The SLN was located intraoperatively by means of a gamma probe and excised. Subsequent pathologic evaluation of the SLN was negative for evidence of metastatic SCC by light microscopy with hematoxylin and eosin, and with immunohistochemical stains for cytokeratins AE1 and AE3. The day after SLN excision, the tumor was removed via Mohs micrographic surgery with clear surgical margins after a total of 8 stages. Aggressive subclinical spread by both subcutaneous "skating" and perineural invasion was noted. CONCLUSION: The combination of Mohs micrographic surgery and sentinel lymphadenectomy is feasible and has theoretical utility in the management of a subset of cutaneous SCCs at high risk for metastasis. The ability of sentinel lymphadenectomy to identify regionally metastatic cutaneous SCC as well as the additive benefit of SLN and Mohs micrographic extirpation in the treatment of high-risk cutaneous SCC remain to be further clarified.     

Cutaneous lymphadenoma: report of 2 cases.

Cutaneous lymphadenoma is a recently described tumor with a distinctive histological picture associating a basaloid epithelial proliferation and intraepithelial lymphocytes; it seems to represent a benign adnexal neoplasm of uncertain histogenesis. We documented 2 additional examples of cutaneous lymphadenoma with typical histological features; the contiguity of some tumor lobules with preexisting follicular structures was noted. In 1 case, a cutaneous osteoma was present below the tumor. On immunostainings, S-100 protein revealed numerous dendritic intraepithelial and stromal cells. The basaloid proliferation was positive for broad-spectrum keratin antibodies, but negative for KL1 antibody. In addition, several areas were positive for involucrin within tumor lobules. Our findings are consistent with a pilosebaceous origin of cutaneous lymphadenoma.     

A case of porocarcinoma arising in pigmented hidroacanthoma simplex with multiple lymph node,liver and bone metastases

Porocarcinoma is a rare skin appendage carcinoma that may arise de novo or be associated with pre‐existing poroma and hidroacanthoma simplex (HAS). Here, we report a case of porocarcinoma arising in pigmented HAS, which led to death from multiple lymph node, liver and bone metastases. A 72‐year‐old Japanese man presented with a brown to focal black flat plaque, measuring 17 × 12 mm, on the posterior region of his right thigh. Histopathological study of the tumor revealed that there was intraepidermal proliferation of small‐sized basaloid cells, and it exhibited the ‘Jadassohn phenomenon’, with dendritic melanocytes, and a few ductal structures were observed. Continuing to the intraepidermal nests, the invasive proliferation of large polygonal cells with occasional intracytoplasmic ductal structures was observed. Carcinoembryonic antigen and epithelial membrane antigen were expressed in some carcinoma cells and they highlighted the intracytoplasmic ductal structures. Multiple lymph node, liver and bone metastases were observed, and the patient died 8 months after the initial surgery. Clinical diagnosis of HAS is extremely rare. Porocarcinoma may be associated with pre‐existing HAS and sometimes shows aggressive behavior. Therefore, pigmented HAS must be included in the differential diagnosis of brown or black lesions. Ishida M, Hotta M, Kushima R, Okabe H. A case of porocarcinoma arising in pigmented hidroacanthoma simplex with multiple lymph node, liver and bone metastases.     

Case of low‐grade neuroendocrine carcinoma of the skin presenting metastases to lymph nodes and peritoneum

A 61‐year‐old Japanese man had a gradually growing, red‐colored nodule in his umbilicus from 3 years ago. He had no symptoms such as hot flush, diarrhea or wheezing. Computed tomography detected a 3.0 cm × 3.0 cm enhanced nodule on the umbilical portion, inguinal and axillary lymph node swelling, and peritoneal nodules. Upper and lower gastrointestinal endoscopy and cystoscopy did not show any other tumor. We resected the umbilical nodule and subjected the inguinal lymph node and peritoneal nodule to biopsy. Histopathological findings indicated that the cutaneous lesion was composed of variously sized nests that included small, monomorphic, round to polygonal cells, mainly in the dermis to the peritoneum. Mitotic figures were scant. The inguinal lymph node and peritoneal nodule were positive for metastasis. Immunohistochemistry was diffusely positive for cytokeratin (CK)‐7, CD56, chromogranin A, synaptophysin, estrogen receptor‐α, progesterone receptor, GATA3 and carcinoembryonic antigen, and focally positive for mammaglobin and gross cystic disease fluid protein 15. The Ki‐67 labeling index was 1.5%. The patient was diagnosed with a case of low‐grade neuroendocrine carcinoma of the skin (LGNECS) occurring on the umbilicus. This case exhibited distant peritoneal metastasis, as well as inguinal and axillary lymph node metastases; however, the patient is alive without chemotherapy at 23 months after the first visit. LGNECS is a newly proposed, extremely rare entity that has been reported under various names, including primary cutaneous carcinoid tumor. In the present case, this tumor shows a slow‐growing nature and favorable prognosis, even though it harbors metastatic potential.     

A case of cutaneous myoepithelial carcinoma

BACKGROUND: Cutaneous myoepithelioma, both benign and malignant, is a rare neoplasm composed of neoplastic myoepithelial cells showing diverse histopathological features, and criteria for discriminating benign or malignant have not been fully clarified. PATIENT: We present a case of cutaneous myoepithelial carcinoma in a 62-year-old woman presenting a solid mass in the right back. RESULTS: Resected tumor was located in the whole dermis and subcutis. Histopathologically, two different growth patterns were noted: a small-nested or trabecular pattern in the superficial part and a large nodular pattern with extensive central necrosis in the deep part. Tumor cells were all epithelioid, although plasmacytoid and glycogen-rich clear cells were also observed within the large nodules of the deep part. Immunohistochemically, the cells were positive for both epithelial and myogenic markers, suggesting myoepithelial origin. Lymphatic invasion and lymph node metastasis were evident despite inconspicuous atypia and low mitotic rate. CONCLUSION: The final diagnosis was cutaneous myoepithelial carcinoma. At present, it seems to be difficult to predict the behavior of myoepithelioma of the skin and soft tissue, although atypia and high mitotic rate are reported to be associated with local recurrence and metastasis.     

Local recurrence of cutaneous mixed tumor (chondroid syringoma) as malignant mixed tumor of the thumb 20 years after initial diagnosis

Benign cutaneous mixed tumor (chondroid syringoma) is the cutaneous counterpart of the benign mixed tumor (pleomorphic adenoma) of salivary glands, consisting of both epithelial and mesenchymal elements. The incidence of cutaneous mixed tumor is rare, composing <0.01% of all primary skin tumors. Herein, we report a case of malignant mixed tumor which recurred in the right thumb 20 years after the reported initial diagnosis of a benign mixed tumor at this site. Histologically, the lesion consisted of highly atypical and infiltrative cells in cords and ductal structures, with an adjacent focus of residual benign mixed tumor present. Perineural invasion of multiple dermal and subcutaneous nerves was also seen. Immunohistochemical staining was strongly and diffusely positive for CK5/6 and p63, with patchy positive S100 and CK7 staining. Wide excision was performed, with no evidence of recurrence or metastasis 5 years later.     

CD20‐Positive nodal natural killer/T‐cell lymphoma with cutaneous involvement

CD20‐positive natural killer (NK)/T‐cell lymphoma is extremely rare. We describe a case of a CD20‐positive nodal NK/T‐cell lymphoma with cutaneous involvement in a 32‐year‐old man. The patient presented with fever, night sweats, right inguinal lymphadenopathy and multiple violaceous to erythematous nodules and plaques on the back and bilateral legs. Immunohistochemical analysis showed diffusely and strongly positive staining for CD3, CD3 epsilon, CD43, CD56, TIA‐1 and CD20 but negative staining for other B‐cell markers, including CD79a and PAX‐5 and T‐cell markers CD5 and CD7. The tumor cell nuclei were diffusely positive for Epstein–Barr virus‐encoded RNA in situ hybridization. A partial clinical response was observed after chemotherapy, indicated by the decreased size of the lymph nodes and skin lesions. It is a diagnostic challenge to deal with lymphoma cells that present with the surface proteins of both T‐ and B‐cells.