Numerous multinucleated giant cells in cutaneous epithelioid angiosarcoma and pulmonary metastasis: A unique observation with potential diagnostic pitfalls.

The histopathologic diagnosis of poorly differentiated cutaneous angiosarcoma can be challenging. We report a case of cutaneous epithelioid angiosarcoma with numerous multinucleated giant cells (MGCs) developing pulmonary metastasis. A 79-year-old man presented with a red-purple plaque on the scalp. A skin biopsy revealed epithelioid cell proliferation, admixed with numerous MGCs, and background hemorrhage. Vascular spaces were focally present and lined by atypical endothelial cells, including MGCs. Immunohistochemically, tumor cells, including MGCs, were positive for CD31, D2-40, and ERG. The patient received radiation therapy and chemotherapy, after which a follow-up CT scan revealed symptomless pneumothorax and pulmonary metastases. The patient received palliative partial lung resection, and the specimen revealed histopathological and immunohistochemical features similar to the primary cutaneous lesion. Our report expands the morphologic spectrum of cutaneous epithelioid angiosarcoma. Cutaneous angiosarcoma is an aggressive neoplasm; thus, awareness of this rare manifestation is important.

Trichilemmal cysts with proteinaceous material: A potential diagnostic pitfall.

BACKGROUND: Cysts of the skin are observed frequently and their diagnoses are generally straightforward. However, atypical cystic lesions for which differentiation is indistinct have been noted. METHODS: We examined five cases of trichilemmal cyst with proteinaceous material (TCPM), which required differentiation from sweat duct/gland tumors. We investigated the histopathological findings of TCPMs and evaluated the immunohistochemical expression of cytokeratin (CK) 10, CK13, CK17, CK19, CD8, and CD117. Immunohistochemical analysis was performed on the 5 TCPMs, 10 trichilemmal cysts (TCs), 5 clear-cell hidradenomas, 5 poroid hidradenomas, and cutaneous normal adnexa. RESULTS: Apoptotic cells were present in the cyst wall with a small amount of keratin or calcification in the cavity of TCPMs. The TCPMs and TCs were negative for CK19 and CD117, on the other hand clear-cell hidradenoma and poroid hidradenoma were positive for CK19 and CD117. The restricted positivity for CK10 was detected in the suprabasal layers of the cyst walls of TCPMs and TCs. The immunostaining patterns of TCPMs and TCs were similar to those of normal follicular isthmus. CONCLUSIONS: The histopathological findings with characteristics of TCs and a panel of immunohistochemical antibodies including CD117, CK19, and CK10 contributed to a correct diagnosis of TCPM.

A case of cutaneous syncytial myoepithelioma with extensive adipocytic metaplasia: Usefulness of EWSR1-PBX3 gene fusion analysis.

Cutaneous syncytial myoepithelioma (CSM) is a recently recognized variant of myoepithelioma characterized by an intradermal syncytial proliferation of spindled, ovoid, and histiocytoid cells. Immunohistochemically, tumor cells usually show strong expression of S-100 protein and epithelial membrane antigen (EMA). Here we report a case of CSM in the thigh of a 51-year-old Japanese woman. Histopathological findings showed a sheet-like growth of ovoid cells and histiocytoid cells with an eosinophilic syncytial cytoplasm, and adipocytic metaplasia was widely observed in the tumor. Immunohistochemical staining revealed a diffuse, strong pattern for EMA, smooth muscle actin (SMA), and HHF35, and variable expression of S-100 protein and p63 in ovoid and histiocytoid cells without significant mitotic figures or pleomorphism. In addition, EWSR1-PBX3 gene fusion, which is characteristic of CSM, was observed in the tumor. Based on these findings, we diagnosed the patient as having CSM. Our case shows that CSM can exhibit extensive adipocytic metaplasia, which could make its histopathological diagnosis challenging.

Ln-γ 2 chain of laminin-332 is a useful marker in differentiating between benign and malignant sclerosing adnexal neoplasms.

AIMS: Laminin (Ln)-γ 2, one of the chains of Ln-332, is a marker of invasive tumours and is frequently expressed as a monomer in malignant tumours. Desmoplastic trichoepithelioma (DTE), some types of basal cell carcinoma (BCC) (infiltrating and morphoeic BCC) and microcystic adnexal carcinoma (MAC) belong to a group of tumours known as sclerosing adnexal neoplasms (SAN) that are frequently difficult to differentiate and often require immunohistochemistry for diagnosis. The aim of this study was to assess the usefulness of Ln-γ 2 expression in the differential diagnosis of DTE, infiltrating/morphoeic BCC, MAC and syringoma. METHODS AND RESULTS: In this study, we compared the expression of Ln-γ 2 in infiltrating/morphoeic BCC (n = 28), DTE (n = 26), MAC (n = 10) and syringoma (n = 20). Immunohistochemically, Ln-γ 2 positivity was noted in 96% (27 cases) of infiltrating/morphoeic BCC and 90% (nine cases) of MAC, while all DTE and syringoma cases were negative. Furthermore, Ln-γ 2 expression pattern in infiltrating/morphoeic BCC was different from that in MAC. Ln-γ 2 expression was found in the cytoplasm of tumour cells in infiltrating/morphoeic BCC tumour cells, while in MAC linear expression was noted both along tumour nests and in the cytoplasm. CONCLUSION: Ln-γ 2 is a helpful adjunct in the differential diagnosis of SAN.

Tubulopapillary Cystic Adenoma With Apocrine Differentiation: A Unifying Concept for Syringocystadenoma Papilliferum, Apocrine Gland Cyst, and Tubular Papillary Adenoma.

Syringocystadenoma papilliferum (SCAP), apocrine gland cyst (AGC, also called apocrine hidrocystoma or apocrine cystadenoma), and tubular papillary adenoma (TPA) with apocrine differentiation are defined as proliferations of apocrine epithelium with myoepithelial cells. At Sapporo Dermatopathology Institute, we retrieved 308 benign neoplastic lesions diagnosed as SCAP, AGC, or TPA and combinations of these entities. Among the 308 lesions, 202 (66%) exhibited features of only one type, of which 144 (47%) were AGC, 39 (13%) were TPA, and 19 (6%) were SCAP. The other 106 lesions (34%) had features of 2 or more types, including 56 lesions that were AGC + TPA (18%), 2 that were AGC + SCAP (1%), 34 that were TPA + SCAP (11%), and 14 that were AGC + TPA + SCAP (5%). The most frequent site of these lesions was the face (56%), followed by the scalp (13%). Lesions with the features of AGC were more frequently found on the face, especially the periocular region, than at other sites. TPA lesions were more frequent on the face and scalp than at other sites, whereas SCAP lesions were preferentially found on the face, scalp, and trunk. We also retrieved clinicopathological data and other information. We propose a unifying concept for AGC, TPA, and SCAP. Approximately one-third of these lesions are composite entities with the features of 2 or 3 different tumors, and we propose calling such tumors tubulopapillary cystic adenoma with apocrine differentiation.

Carcinoid-Like/Labyrinthine Pattern in Sebaceous Neoplasms Represents a Sebaceous Mantle Phenotype: Immunohistochemical Analysis of Aberrant Vimentin Expression and Cytokeratin 20-Positive Merkel Cell Distribution.

This study investigated the nature of carcinoid-like, labyrinthine, rippled, and conventional cell arrangements in sebaceous neoplasms, focusing on vimentin expression and Merkel cell distribution in sebaceous neoplasms relative to these findings in normal sebaceous units and other sebaceous conditions. Immunohistochemistry for vimentin and cytokeratin 20 (CK20) was evaluated in carcinoid-like (n = 2), labyrinthine (n = 4), rippled (n = 3), and conventional (n = 6) sebaceomas; sebaceous mantle hyperplasia (n = 1); steatocystomas (n = 5); fibrofolliculomas (n = 4); sebaceous mantleoma (n = 1); sebaceous gland hyperplasias (n = 4); sebaceous adenomas (n = 4); and sebaceous carcinomas (n = 4) as well as normal skin tissue. The sebaceous mantle and its hamartoma (fibrofolliculoma) showed weak positivity for vimentin in the basal layer of the epithelial component and contained a few CK20-positive Merkel cells within the epithelial component, whereas mature sebaceous lobules were negative for vimentin and did not contain any Merkel cells. All sebaceomas with carcinoid-like or labyrinthine pattern highly expressed vimentin. CK20-positive Merkel cells were distributed with varying numbers in carcinoid-like pattern (2/2) and labyrinthine pattern (3/4) sebaceomas, sebaceous mantle hyperplasia (1/1), steatocystomas (3/5), fibrofolliculomas (3/4), and sebaceous mantleoma (1/1). Vimentin expression and Merkel cell distribution were observed in normal sebaceous mantles and sebaceous mantle-associated lesions, which could be evidence of a sebaceous mantle nature in the limited setting of sebaceous lesions. Furthermore, carcinoid-like/labyrinthine pattern sebaceomas also showed vimentin immunoreactivity and contained Merkel cells. Therefore, carcinoid-like/labyrinthine pattern of cell arrangement in sebaceous neoplasms may represent a morphological phenotype of sebaceous mantles.

Low-Grade Neuroendocrine Carcinoma of the Skin (Primary Cutaneous Carcinoid Tumor) as a Distinctive Entity of Cutaneous Neuroendocrine Tumors: A Clinicopathologic Study of 3 Cases With Literature Review.

There is scarcity of information on primary cutaneous low-grade neoplasms commonly known as carcinoid tumors, owing to their rarity. The authors present 3 cases that were named "low-grade neuroendocrine carcinoma of the skin" (LGNECS). These occurred in the dermis and subcutis of the anterior chest or the inguinal region in the elderly. Histologically, the tumors showed infiltrating proliferation of nests of various sizes, with low-grade neuroendocrine cytologic features but without mucin production. All cases exhibited varying degrees of intraductal tumor components. On immunohistochemical examination, these tumors expressed estrogen receptor alpha, progesterone receptor, androgen receptor, gross cystic disease fluid protein 15, mammaglobin, and GATA3 as well as neuroendocrine markers. Although a literature review revealed 8 additional possible cases with no evidence of other diseases, it was difficult to determine if these were true cases of LGNECS, because of the limited information available. Based on its characteristic histologic features and immunoprofile, it can be proposed designating LGNECS as a distinct entity among cutaneous neuroendocrine tumors. Otherwise, such tumors could be misdiagnosed as mammary carcinomas (particularly when involving the skin of the breast) or as metastatic visceral neuroendocrine tumors of the skin.

CD117 (KIT) is a useful immunohistochemical marker for differentiating porocarcinoma from squamous cell carcinoma.

BACKGROUND: Distinguishing porocarcinoma from squamous cell carcinoma (SCC) is clinically significant but can pose a diagnostic dilemma. The present study sought to confirm the diagnostic utility of CD117 immunohistochemistry in distinguishing porocarcinoma from SCC and to examine histologic, carcinoembryonic antigen (CEA) immunohistochemical and CA19-9 immunohistochemical differences between these tumors. METHODS: Immunostaining with anti-CD117, anti-CEA and anti-CA19-9 antibodies was performed for 22 porocarcinomas and 31 SCCs. The extent of CD117, CEA and CA19-9 staining was classified as negative (<1%), rarely positive (1-4%), focally positive (5-29%) or diffusely positive (30-100%). CD117 staining intensity was semi-quantitatively graded as weak, moderate or strong. RESULTS: All (100%) porocarcinomas were positive for CD117, with mainly focal (8/22) or diffuse (11/22) and moderate (9/22) to strong (8/22) staining. In contrast, only 6 of 31 SCCs (19.4%) expressed CD117 focally, and this expression was limited to the basal layer of the tumor in four cases. CEA immunostaining highlighted the lumina of all 22 porocarcinomas; however, CEA expression was not significantly different between porocarcinomas and SCCs (100 vs. 71.0%, respectively). CA19-9 was not expressed in the lumina of 5 of 22 porocarcinomas. CONCLUSIONS: Along with CEA, CD117 immunohistochemistry could be helpful in distinguishing porocarcinomas from SCCs.

Spiradenocarcinoma in Preexisting Spiradenoma With a Large In Situ Adenocarcinoma Component.

Spiradenocarcinoma is a very rare malignant tumor. In situ adenocarcinoma has recently been observed and defined by the preservation of a peripheral myoepithelial cell layer. The pathway for this phenomenon has been hypothesized to involve a sequence of adenomatous changes followed by atypical adenomatous changes, adenocarcinoma in situ, and invasive adenocarcinoma. However, there are no clearly defined morphological distinctions between atypical adenomatous changes and adenocarcinoma in situ. The authors present a case of spiradenocarcinoma in a preexisting spiradenoma in the left inguinal area of a 71-year-old woman. Adenomatous changes, atypical adenomatous changes, adenocarcinoma in situ, and invasive adenocarcinoma were found within the same lesion. The majority of the malignant component was an in situ adenocarcinoma. Although a loss of the myoepithelial cell layer and coalescing, irregular, glandular nests were present in several discrete foci, this case did not show infiltrative growth beyond the fibrous connective tissue. The authors speculate that this case represents a very early invasive spiradenocarcinoma lesion. We present this case to discuss the histological and/or immunohistochemical criteria of atypical adenomatous changes and to discuss the optimal treatment in cases with a disparity between the preservation of the whole architecture and the loss of the myoepithelial cell layer, which may be associated with favorable biological behavior.

A clinicopathologic and immunohistochemical study of 7 cases of sclerosing perineurioma.

Sclerosing perineurioma is a relatively rare tumor that has remained widely unknown since first reported by Fetsch in 1997. To our knowledge, no large or small series of claudin-1 in sclerosing perineurioma has been confirmed to date. We collected 7 new cases of sclerosing perineurioma. Six patients were female, and 1 was male. The patients' age ranged from 15 to 58 years (mean, 36.6 years; median, 42.0 years). The primary reason for consultation at the outpatient clinics was a slowly enlarging mass. The preoperative durations were available for 4 of the 7 cases and ranged from 2 to 7 years. Six tumors were located in the fingers, and the other tumor was found in the palm. The sizes ranged from 4 to 12 mm in diameter (mean, 6.7 mm; median, 6.0 mm). Microscopically, all tumors were nodular lesions, with sclerotic stroma involving reticular dermis primarily consisting of small oval epithelioid cells and plump spindle cells, scattered and arranged in corded, trabecular, reticular, and/or whorled growth patterns. The neoplastic cells were immunoreactive for epithelial membrane antigen (7 of 7) and glucose transporter 1 (7 of 7). The periodic acid-Schiff reaction and positive immunostaining for type IV collagen were observed directly adjacent to the lesional cells in all cases (6 of 6). Claudin-1 immunostaining was positive in all 7 cases, suggesting that claudin-1 may serve as a helpful diagnostic marker for sclerosing perineurioma.

Relationship among human herpesvirus 6 reactivation, serum interleukin 10 levels, and rash/graft-versus-host disease after allogeneic stem cell transplantation.

BACKGROUND: The relationship between herpesvirus reactivation and graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT) is unclear. OBJECTIVE: We sought to examine the relationship between human herpesvirus (HHV) reactivation and rash/GVHD after allo-SCT by prospective evaluation. METHODS: Fifteen patients who had received allo-SCT underwent prospective serial examinations for human herpesvirus 6 (HHV-6), HHV-7, cytomegalovirus, and Epstein-Barr virus DNA in the blood by polymerase chain reaction and real-time polymerase chain reaction. Serum interferon gamma, interleukins 4 and 10, tumor necrosis factor alpha, and soluble interleukin 2 receptor (sIL-2R) were also measured. RESULTS: In 10 of 15 patients, macular/papular eruptions were seen after allo-SCT and GVHD was diagnosed. In 8 patients with rash, HHV-6 DNA levels correlated with the cutaneous manifestation. Interleukin 10 and sIL-2R also increased in association with rash. LIMITATIONS: The number of patients in our study was relatively small. Not all patients were examined for cytokines and sIL-2R. CONCLUSIONS: HHV-6 reactivation may be involved in the pathogenesis of rash/GVHD after allo-SCT.

Dermoscopic features of endocrine mucin-producing sweat gland carcinoma.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is very rare, with only 61 cases reported to date. EMPSGC is considered to be a low-grade carcinoma of sweat gland origin. Dermoscopic findings of EMPSGC have not been previously reported. We report the first case of a man with EMPSGC, featuring dermoscopic findings. Dermoscopic examinations of the present EMPSGC lesion revealed tumor cell proliferation that appeared as pink ovoid nests and elongated epidermis that resembled a whitish-pink network. Another characteristic finding of the present lesion was the large red/blue globules in pink ovoid nests in the tumor. Those reflected lacunae containing secretory fluid with red blood cells. We think that the large red/blue globules in pink ovoid nests in our case could be a characteristic dermoscopic finding specific to EMPSGC. We dermatologists encounter many "pink nodules" at out-patient clinics. The present dermoscopic findings may be useful for the differential diagnosis of EMPSGC.

Paraneoplastic pemphigus presenting as erythrodermic lichenoid dermatitis with concomitant features of pemphigus foliaceus.

We describe a patient with paraneoplastic pemphigus who presented with erythrodermic lichenoid dermatitis, later developing blisters of pemphigus foliaceus type and oral erosive lesions. In addition to antibodies against the plakin family proteins, the patient's serum was positive for anti-desmoglein 1 antibodies without coexisting anti-desmoglein 3 activities by enzyme-linked immunosorbent assay, which is a very rare autoantibody profile in paraneoplastic pemphigus.