Chronological changes in trichofolliculoma: Folliculosebaceous cystic hamartoma is not a very-late-stage trichofolliculoma.

Some authors have reported that the secondary hair follicles in trichofolliculomas (TF) undergo regressive changes and are subsequently replaced by the developed sebaceous elements, and that folliculosebaceous cystic hamartoma (FSCH) is a TF at a very late stage. In the present study, we revaluated the histopathological features of 40 TF lesions, focusing on their chronological changes. The results of the present study indicate that while the secondary follicles in the TF exhibited the hair cycle, the normal hair cycle was out of control, and tertiary hair follicles randomly developed from the involuting secondary follicles. The repeated development of hair follicles in this disordered hair cycle caused the development of chains of several continuous hair follicles in late-stage TF. In the TF lesions, no features indicating the replacement of the regressing secondary hair follicles by any sebaceous elements were observed, thereby suggesting that FSCH is not a very-late-stage TF.

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.

Localized Subcutaneous Insulin-Derived Amyloidosis Excised after Evaluation Using Ultrasonography in a Patient with Type 2 Diabetes Mellitus.

A 62-year-old man with type 2 diabetes mellitus, who had been on insulin therapy for the past 20 years, was found to have subcutaneous mass formation in the abdomen during a workup of worsened glycemic control. Because of suspected amyloid deposition, he was advised to avoid injections to the mass, which led to improvement of glycemic control. However, he strongly requested mass excision and was hospitalized. After evaluation using ultrasonography and computed tomography, a total mass excision was performed, and a diagnosis of insulin-derived amyloidosis was made. Comparison of the ultrasonographic and histopathological findings demonstrated that the location of the amyloid deposition nearly corresponded to the hypoechoic region. This case highlights that ultrasonography, which is a noninvasive imaging modality, can be useful for detection of insulin-derived amyloidosis.

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.

Two cases of seborrheic keratosis with basal clear cells.

Seborrheic keratosis with basal clear cells (SKBCC) is an extremely rare histopathological variant of seborrheic keratosis that has histological similarities to melanoma in situ. We herein report two cases of SKBCC and provide the first description of the dermoscopic features of this condition, in addition to the histopathological findings. Both of the two lesions showed typical histological architectures of seborrheic keratosis with rows or focal clusters of monomorphic clear cells with abundant pale cytoplasm and small round nucleus in the basal layer. Immunohistochemical examination revealed that most clear cells were positive for high molecular weight cytokeratin (34ßE12) in a peripheral pattern but were negative tor Melan-A. Dermoscopy revealed typical features of ordinary seborrheic keratosis, while unfortunately did not reflect the presence of basal clear cells.

Clinicopathological analysis of 384 cases of poroid neoplasms including 98 cases of apocrine type cases.

We examined 384 cases of poroid neoplasms. Most cases (n = 279, 72.7%) exhibited the features of only one subtype. One hundred and ninety-eight cases (51.6%) showed only the features of poroma (P), 20 (5.2%) hidroacanthoma simplex (HS), five (1.3%) dermal duct tumor (D) and 56 (14.6%) hidradenoma (HA). Composite tumors of those four subtypes were observed in 105 cases (27.3%). In the trunk and lower extremities, lesions with the features of P were observed at higher rates than other sites. Those of HS and D were more frequently observed in the lower extremities. Those of HA were seen at higher rates in the scalp, face, neck and genitalia. Ninety-eight cases (25.5%) showed decapitation secretion and diagnosed as apocrine type lesion. Apocrine type lesions were frequently observed in the lesions on the genitalia (40.0%), scalp (31.8%) and trunk (31.1%), whereas at lower rates in those on the neck (21.4%) and lower extremities (24.0%). In apocrine type cases, the lesions were located more frequently on the scalp and trunk than non-apocrine type, whereas were less frequent on extremities. The rate of apocrine type lesions in the cases with only one subtype (19.7%) was lower than that of those with composite tumors (41.0%). In the apocrine type (43.9%), composite tumors are more frequent than in the non-apocrine type (21.7%). In D (40.8%) and HA (32.3%), apocrine type lesions were more frequently observed than other subtypes. In conclusion, it should be noted that a quarter of poroid neoplasms are composite tumors and/or show apocrine differentiation.

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.

Four Japanese cases of dendritic cell neurofibroma with pseudorosettes.

Dendritic cell neurofibroma with pseudorosettes (DCNWPR) is a rare peripheral nerve sheath tumor (PNST). To our knowledge, the only reported case of DCNWPR in Japan was documented by our team. We experienced three additional cases of DCNWPR in our institute since 2007, and report the clinical and histological features of DCNWPR of these Japanese cases. All four patients were adult women, with ages ranging 48-77 years (mean, 63.8). All patients presented with small solitary lesions that were clinically diagnosed as fibroma, melanocytic nevus or mixed tumor of the skin. Three cases were located on the back, and one on the cheek. Histopathologically, well-circumscribed nodules were present in the dermis, and composed of small lymphocyte-like cells with dark nuclei (type I cells) and larger cells with pale vesicular nuclei and abundant eosinophilic cytoplasm (type II cells). Small type I cells were grouped concentrically around the larger type II cells, thereby forming pseudorosettes. Immunohistochemical studies using antibodies against CD57 and S100 protein revealed that type II cells contained a copious cytoplasm endowed with a network of slender dendritic extensions. CD57 should be a useful marker for identifying type II cells because it allows these cells to be stained exclusively. We should recognize DCNWPR with its characteristic histological features such as pseudorosettes and presence of dendritic type II cells as a variant of PNST.

Three cases of reconstruction with a simply designed bilobed flap after excision of squamous cell carcinomas of the lateral eyebrow areas.

Squamous cell carcinoma is frequently observed on the lateral eyebrow, one of the most difficult sites for one-stage reconstruction because of its location close to the eyelids. The reconstruction of defects by the single-stage flap is advantageous for elderly patients because of its good functional and aesthetic outcome. We surgically treated three cases of squamous cell carcinoma on this area and performed reconstruction with a simply designed bilobed flap, all of which resulted in favorable outcomes. We therefore report on the usefulness of this reconstructive method for the lateral eyebrow defects.

Ber-EP4 is a useful marker for follicular germinative cell differentiation of cutaneous epithelial neoplasms.

Ber-EP4 is a monoclonal antibody that recognizes 34-kDa and 39-kDa non-covalently linked glycopolypeptides expressed by most human epithelial cells and carcinomas. In this study, we performed immunohistochemical staining of 31 cases of basal cell carcinoma (BCC); 20 cases of trichoblastoma (TB), including ten cases of nodular type, eight cases of cribriform type (trichoepithelioma) and two cases of columnar type (desmoplastic trichoepithelioma); 16 cases of actinic keratosis (AK); and 10 cases each of Bowen's disease, poroma and seborrheic keratosis. Six cases of BCC and AK were co-lesions of both neoplasms. In normal skin tissue, Ber-EP4 reacted positively with the secretory portion of eccrine glands and follicular germinative cells at the lower end of catagen hairs. Neoplastic cells in 97% of cases with BCC reacted positively with Ber-EP4 in at least 5% of neoplastic cells. Those in 90% with nodular type TB and 50% with trichoepithelioma also reacted positively in at least 5% of neoplastic cells. No cases of poroma, seborrheic keratosis, AK or Bowen's disease were immunohistochemically positive for Ber-EP4 in neoplastic cells. In all six cases with co-lesions of BCC and AK, neoplastic cells of BCC reacted positively with Ber-EP4 and those of AK were negative. Immunohistochemical examination using the Ber-EP4 antibody is a useful tool for diagnosing neoplasms with follicular germinative differentiation, such as TB, TE or BCC, and for differentiating those from squamous cell carcinoma in situ, poroma or seborrheic keratosis.

Sebaceous carcinoma: an immunohistochemical reappraisal.

The rates of distant metastases and tumor death in sebaceous carcinoma (SC) have been reported to be higher than those of other cutaneous carcinomas, such as squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), regardless of whether they occur in ocular or extraocular regions. Therefore, strict differentiation of SC from SCC and BCC is required. In this article, we report immunohistochemical findings of SC and compare these data to those of SCC, BCC, and sebaceoma. An immunohistochemical study was performed using 7 antibodies [anti-carcinoembryonic antigen (CEA), anti-epithelial membrane antigen (EMA), anti-CA15-3, anti-CA19-9, anti-androgen receptor (AR), anti-epithelial antigen (Ber-EP4), and anti-adipophilin (ADP)] on 35 cases of SC (16 cases in ocular and 19 cases in extraocular regions) and 10 cases of each SCC (5 cases in ocular and 5 cases in extraocular regions), BCC (5 cases in ocular and 5 cases in extraocular regions), and sebaceoma (no cases arose on the eyelids). In summary, the typical immunophenotypes of SC were EMA+, CA15-3+, AR+, Ber-EP4-, and ADP+; those of sebaceoma were CEA-, EMA+, Ber-EP4-, and ADP+; those of SCC were CEA-, EMA+, CA19-9-, AR-, Ber-EP4-, and ADP-; and those of BCC were CEA-, EMA-, CA15-3-, Ber-EP4+, and ADP-. Other antibody tests for each neoplasm were positive in about half of the cases. The detection of AR and ADP was useful for differentiating SC from SCC, whereas the determination of EMA, CA15-3, Ber-EP4, and ADP was valuable in differentiating SC from BCC.

Immunohistochemical findings of sebaceous carcinoma and sebaceoma: retrieval of cytokeratin expression by a panel of anti-cytokeratin monoclonal antibodies.

This study examined immunohistochemical findings of sebaceous carcinoma and sebaceoma. An immunohistochemical study using 13 anti-cytokeratin (CK) antibodies (anti-CK1, 5-8, 10 and 14-20) and 35 cases of sebaceous carcinoma (16 cases on ocular and 19 cases on extraocular regions) and 10 cases of sebaceoma (no cases arose on the eyelids) was performed. Overall, those in ocular lesions were almost the same as those for extraocular lesions in sebaceous carcinoma other than CK8. The findings in sebaceous carcinoma were almost equal to those of sebaceoma. Over 75% of cases with sebaceous carcinoma were positive with anti-CK5 and anti-CK14 antibodies and negative with anti-CK1, CK10, CK15, CK17, CK18 and CK20 antibodies. Most cases (50-75%) of those were positive with CK7 and negative with CK6, CK16, CK19 and CK8. The sensitivity and specificity of immunohistochemical detection of sebaceous carcinoma using the panel of anti-cytokeratin antibodies were lower than those of other antibodies. Immunohistochemical detection of cytokeratins in diagnosing sebaceous carcinoma should be considered to be ancillary to conventional microscopic findings and those of other antibodies.

Cytokeratin expression patterns in multiple infundibulocystic basal cell carcinoma.

Infundibulocystic basal cell carcinoma (IBCC) is a variant of basal cell carcinoma. Sporadic cases usually represent a solitary tumor and multiple IBCC is rare. There have been no reports in which the tumor differentiation is characterized immunohistochemically. We report a case of multiple IBCC which developed on a patient's scalp by performing histopathological and immunohistochemical examinations, using monoclonal antibodies against cytokeratins (CKs). A 76-year-old female had noticed multiple small papules on her scalp. She noticed that the tumors were growing when she underwent systemic chemotherapy for metastatic lung cancer. Routine histopathological specimens from skin biopsies revealed findings typical of IBCC. The tumor cells expressed CK14 and CK17. However, CK1 and CK10 were expressed only in a few cells in the inner area of the tumors. The present case is unique in two points. First, multiple tumors developed on the patient's scalp during the systemic chemotherapy for the lung cancer. Second, the tumor showed CK expression patterns characteristic to infundibular and trichilemmal epithelia.

A clinicopathologic study of folliculosebaceous cystic hamartoma.

Folliculosebaceous cystic hamartoma (FSCH) is a distinctive cutaneous hamartoma of follicular, sebaceous, and mesenchymal components. Only 70 cases of FSCH have been reported in the literature since the original report of 5 cases in 1991. There has been little information reported about the clinicopathologic characteristics of FSCH. We summarize the clinicopathologic features of 153 cases of FSCH that were diagnosed histopathologically at Sapporo Institute for Dermatopathology. The 153 cases of FSCH comprised 92 male and 61 female patients. The typical clinical presentation of FSCH revealed solitary and skin-colored, protruding papules or nodules measuring several millimeters in diameter on the face, especially on the nose, of middle-aged or older persons. These cases fulfilled the common denominators for the histopathologic diagnosis of FSCH as Kimura et al reported. Seven of 153 cases (4.6%) were accompanied by distinctive features of Miescher-type melanocytic nevi. All 7 cases showed lesions on face, especially on or around the nose. We consider that Miescher-type melanocytic nevi play a significant role in the pathogenesis of FSCH, at least in some cases.

Interstitial type granuloma annulare associated with Sjögren's syndrome.

We describe a case of granuloma annulare (GA) associated with Sjögren's syndrome (SS) in a 69-year-old woman. She complained of erythematous plaques on the left forearm and neck in addition to dry eyes and mouth. The laboratory and clinical findings also fulfilled the criteria for diagnosis of SS. Histopathological examination revealed the features of interstitial type GA. It is not rare that granulomatous diseases are associated with autoimmune diseases. This case indicated that granulomatous diseases and SS are closely related and that GA should be recognized as a cutaneous manifestation associated with autoimmune diseases, including SS.