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.

Distribution of CD1a-positive cells is not different between pseudolymphomatous folliculitis and primary cutaneous marginal zone lymphoma.

Pseudolymphomatous folliculitis (PLF) is a subtype of cutaneous pseudolymphoma that is recognized as an independent disease. PLF is characterized by dermal lymphocytic infiltration surrounding an irregular hyperplastic pilosebaceous unit (i.e., activated pilosebaceous unit). An interstitial distribution of CD1a-positive cells is regarded as an important feature of PLF, especially in distinguishing it from primary cutaneous marginal zone lymphoma (PCMZL), which is associated with a peripheral concentration of CD1a-positive cells. We undertook a clinicopathological investigation of PLF, with a reassessment of CD1a immunohistochemistry. We defined diagnostic criteria for PLF based on past studies and consequently identified 79 cases. In addition, we collected 32 cases of PCMZL and performed detailed clinical, pathological, and immunohistochemical investigations using antibodies to CD3, CD20, and CD1a. We found an interstitial concentration of CD1a-positive cells in 90.2% of PLF and 34.5% of PCMZL cases. The peripheral concentration of CD1a-positive cells was seen in 9.8% of PLF and 34.5% of PCMZL cases. In both diseases, CD1a-positive cells appeared in T-cell nests (88.5% in PLF and 92.9% in PCMZL) but were absent in B-cell nests (0% in both groups). All 79 cases of PLF showed activated pilosebaceous units while 22 of the 32 PCMZL cases displayed pilosebaceous units, although none of these were activated. In summary, regarding the distribution patterns of CD1a-positive cells as a diagnostic feature in distinguishing between PLF and PCMZL is somewhat inconclusive. To differentiate PLF and PCMZL, determining the presence or absence of activated pilosebaceous units is essential.

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.

Aluminum Chloride-Induced Apoptosis Leads to Keratinization Arrest and Granular Parakeratosis.

Aluminum chloride (AlCl3) is the main active ingredient in commonly used antiperspirant. Antiperspirant use may cause a rare keratinization disease, granular parakeratosis (GP), then AlCl3 may be associated with the etiology of GP. The objective of this study is to elucidate the skin effect of topical aluminum application using a mouse model. We sprayed 20% aluminum chloride every day on the depilated mice skin and analyzed the skin clinically, histopathologically, and immunohistologically. We have succeeded in the histological replication of GP on mouse skin. The basophilic granules in the stratum corneum contained filaggrin, and processing of profilaggrin to filaggrin was disrupted in aluminum-treated mouse skin (Al-mouse). In Al-mouse, cytochrome c and cleaved-caspase 3 were upregulated mainly in the granular layer, and caspase 3 p20 subunit was upregulated. TUNEL-positive cells increased significantly in the Al-mouse from the granular to the horny layer. Caspase 3 inhibitor inhibited granular parakeratotic change of Al-mouse. Our results indicated that aluminum-induced apoptosis leads to keratinization arrest and acceleration of nuclear degradation before completion of profilaggrin processing. This could lead to retention of the basophilic granules composed of underprocessed profilaggrin in the horny layer of Al-mouse skin, the hallmark of GP.

Subcutaneous Nodule on the Right Palm of a Young Boy: A Quiz.

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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.

Keratoacanthoma en plaque/nodule: A brief report of the clinicopathological features of five cases.

Keratoacanthoma (KA) is characterized by exoendophytic growth with a central keratin-filled crater, representing the crateriform architecture. We herein report five rare cases of KA without a central keratin-filled crater. These KA cases histopathologically showed that one or a few infundibular structures/isthmic lobules had their own open keratotic pores on the surface without a common merged keratotic plug/horn, clinically representing verrucous (keratotic) plaque/nodule, namely, "KA en plaque/nodule". KA rarely but on occasion does show verrucous plaque (or nodular) lesions without a central keratin-filled crater, as the notion that KA invariably shows crateriform architecture is nonsensical.

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.

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.

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.

Pathological Investigation of Acquired Lymphangiectasia Accompanied by Lower Limb Lymphedema: Lymphocyte Infiltration in the Dermis and Epidermis.

BACKGROUND: Sometimes acquired lymphangiectasia (lymphangioma circumscriptum), the pathological mechanism of which is unknown, accompanies lymphedema. The purpose of this study was to better understand the pathological changes present in acquired lymphangiectasia. METHODS AND RESULTS: We examined the pathological characteristics of acquired lymphangiectasia with lymphedema among patients treated at the University of Tokyo Hospital from March 2008 to December 2015. In total, 16 biopsies from 10 patients were investigated. The average age of the patients was 57.2 years (range 43-69), and all were female with secondary lymphedema. Surgical specimens were fixed in formalin, and tissue sections were stained with hematoxylin-eosin. Additional immunostaining (podoplanin, lymphatic vessel endothelial hyaluronan receptor [LYVE] -1, CD4, CD8, CD20, and CD31) was performed in cases 1-3 and 8-10. Dilation of lymphatic vessels in the papillary dermis was present in all 10 cases. Infiltration of inflammatory cells, most of which were lymphocytes, was also observed in the dermis and the epidermis in all cases, even though there were no clinical signs of inflammation. The infiltrating lymphocytes were mainly CD4+ T cells, and less commonly, CD8+ T cells and CD20+ B cells. The number of three types of lymphocytes was significantly larger in the superficial layer of the dermis than in the deep layer, which may indicate that they oozed out from the dilated lymphatic vessels located in the superficial dermis. CD8+ T cells infiltrated the epidermis in seven of eight specimens. In case 4, coagulated lymphatic fluid inside the lymphatic vessel was observed. Proliferation of collagenous fiber in the dermis and acanthosis were observed. CONCLUSIONS: Lymphatic dilation and proliferation of collagenous fiber in the dermis were seen in cases of acquired lymphangiectasia (lymphangioma circumscriptum). Constant infiltration of lymphocytes in the dermis and the epidermis may have a relation to frequent cellulitis, which is often seen in lymphedema patients.