Apocrine hidradenocarcinoma showing Paget's disease and mucinous metaplasia

A 54-year-old man presented with a solitary, erythematous, rapidly growing 1-cm nodule on his scalp that had arisen over the previous 3 months. He had no history of skin cancer. An excisional biopsy of the lesion showed a fairly well-circumscribed but focally invasive tumor consisting of areas of typical-appearing clear cell hidradenoma as well as areas with mucinous goblet-type cells and cells with eosinophilic cytoplasm and decapitation-type secretion. There was marked cellular atypia, numerous atypical mitotic figures and focal necrosis. The tumor cells focally involved the overlying epidermis (Paget's disease). Large areas of mucin were identified throughout the lesion. The tumor cells stained with markers for cytokeratin 7 and focally for EMA and CEA, confirming ductal differentiation. The goblet cells and mucinous areas stained with mucicarmine and PASD. The patient was diagnosed with hidradenocarcinoma with mucinous differentiation. Associated Paget's disease has only rarely been reported, and mucinous metaplasia is a previously unreported feature in hidradenocarcinoma.     

Benign mucinous metaplasia of the genital mucosa: histomorphological and immunohistochemical features and criteria for differentiation from extramammary Paget disease

Background Benign mucinous metaplasia of the genitalia (BMM) is a rare condition typified by cells with foamy mucinous cytoplasm. Differential diagnoses include extramammary Paget disease (PD) and human papillomavirus (HPV)‐induced vulval intraepithelial neoplasia (VIN) with mucinous differentiation. Objectives To characterize histopathological and immunohistochemical features of BMM and to forge criteria for differentiation from PD and VIN with mucinous differentiation. Methods Eight biopsy specimens of BMM were stained with haematoxylin and eosin, periodic acid–Schiff and alcian blue, and for cytokeratin (CK) 7, CK10, CK14, CK20, carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), S100, gross cystic disease fluid protein‐15 (GCDFP‐15), lysozyme and Ki67 and compared with PD. Polymerase chain reaction was performed in order to identify HPV‐specific DNA. Results BMM showed mucin deposition in superficial epithelial layers ranging from numerous large goblet cells to subtle deposits. The epithelium often showed polygonal (squamoid) or cuboidal differentiation while columnar differentiation was an inconsistent feature. A band‐like inflammatory infiltrate was consistently present. Metaplastic epithelium consistently expressed CK7, CEA and EMA either in the entire epithelium or in a superficial band, while CK14, CK10, GCDFP‐15 and lysozyme were largely not expressed, and staining for CK20 and S100 was negative. Comparison with PD demonstrated similar staining characteristics, but in a scattered pattern of mucinous cells within preserved squamous epithelium and not in a band‐like pattern as in BMM. Nuclear pleomorphism and Ki67‐positive mucinous cells in superficial epithelial layers were seen only in PD; GCDFP‐15 and/or lysozyme were expressed in the majority of cases of PD. No evidence of HPV‐specific DNA was found in BMM. Conclusions The spectrum of changes in BMM is distinctive, and BMM can be differentiated with surety from both PD and VIN with mucinous differentiation.     

Differential expression of mucin core proteins and keratins in apocrine carcinoma, extramammary Paget's disease and apocrine nevus

Background:  Apocrine carcinomas are rare, the immunohistochemical characterizations that are incomplete. The purpose of this study was to determine the immunohistochemical characteristics of mucin core proteins and keratins in apocrine carcinoma, extramammary Paget's disease (EMPD) and apocrine nevus.
Methods:  We report four cases of apocrine carcinomas along with immunohistochemical analyses: (i) an axillary apocrine carcinoma with an apocrine nevus, (ii) an inguinal apocrine carcinoma, (iii) a vulvar apocrine carcinoma with EMPD and (iv) an axillary apocrine carcinoma with EMPD and an apocrine nevus.
Results:  The tumor cells of apocrine carcinomas, EMPD and apocrine nevi displayed a positive reaction to MUC-1 and CK7 and a negative reaction to CK20. Apocrine carcinomas had high molecular weight (HMW) cytokeratin(+)/CK5(+)/CK14(−)/MUC5AC(−), EMPD with underlying apocrine carcinoma had HMW cytokeratin(−)/CK5(−)/CK14(−)/MUCA5AC(−) and the apocrine nevi had HMW cytokeratin(+)/CK5(+)/CK14(+)/MUCA5AC(+).
Conclusion:  The immunohistochemical findings suggest that apocrine carcinomas, apocrine nevi and EMPD with underlying apocrine carcinomas are quite different, even though they are all derived from apocrine glands.     

Cutaneous gamma‐delta T‐cell lymphoma with central nervous system involvement: report of a rarity with review of literature

Primary cutaneous gamma‐delta (γδ) T‐cell lymphoma is an extremely rare and aggressive variant of cutaneous lymphoma. Central nervous system (CNS) involvement, a rare finding, and hemophagocytic syndrome are two complications that are commonly fatal. We describe a 58‐year‐old patient presenting with skin plaque who subsequently developed subcutaneous nodules diagnosed as cutaneous T‐cell lymphoma (CTCL), clinically resembling ‘mycosis fungoides’. The patient was treated with repeat topical radiation therapies but had frequent relapsed disease. Approximately 4.5 years after, the patient presented with third and sixth cranial nerve palsies and was found to have CNS involvement by lymphoma per positron emission tomography—computed tomography (PET/CT) and a biopsy of foramen magnum. Phenotypically, the tumor cells were CD3(+)/CD4(?)/CD8(?)/CD7(+)/CD5(?)/CD30(?)/TCRαβ(?)/TCRγδ(+). Despite aggressive strategies taken, the patient expired 3 months after the diagnosis of the CNS lesion. A retrospective investigation proved the original CTCL to be γδ T‐cell in origin, confirming an indolent cutaneous γδ T‐cell lymphoma with eventual CNS manifestation. We present this case to draw attention to the entity, which can occasionally present with misleading histopathologic and clinical features. In addition, we provide a review of the literature to summarize clinical and pathologic features of the reported similar cases.     

CD34+ dermal dendritic cells and mucin deposition in dermatomyositis

Dermal mucinosis is often associated with collagen diseases such as rheumatoid arthritis, lupus erythematosus, and dermatomyositis, in addition to autoimmune thyroiditis. We report eight cases of dermal mucin deposition secondary to typical dermatomyositis with cutaneous lesions known as heliotrope rash and Gottron’s papules. Striking mucin deposition was observed in both the papillary dermis and reticular dermis of all biopsy specimens. Immunohistochemical analysis showed that CD34+ dermal dendritic cells (DDCs) in the perilesional area in combination with vimentin+ cells within the mucinous lesion might be important in giving rise to abnormal deposition of dermal mucin. On the other hand, numbers of factor XIIIa+ DDCs and tryptase+ mast cells were reduced within and surrounding the mucin deposition, as compared with those in the dermis of normal controls. A pathogenic mechanism of dermal mucin deposition is proposed.     

Lymph node location of a clear cell hidradenoma: report of a patient and review of literature

Cutaneous clear cell hidradenoma is an uncommon benign adnexal tumor which is not supposed to metastasize, contrary to its rare malignant counterpart, hidradenocarcinoma. We report the case of a 49‐year‐old man, who had had a stable inguinal lymph node enlargement for 6 years. An excision was performed and revealed an intra‐nodal tumor, made of large clear cells with abundant cytoplasm and round nuclei without atypia or mitosis. The immunohistochemical staining showed diffuse positivity for keratin AE1/AE3, keratin 5/6 and p63, and focal staining with keratin 7, epithelial membrane antigen (EMA) and carcinous epithelial antigen (CEA), which underlined some ductular structures. Tumor cells were negative for renal markers PAX8 and CD10. Ki67 stained less than 1% of tumor cells. A translocation involving MAML2 gene was evidenced by fluorescence in situ hybridization (FISH) analysis. No primary cutaneous tumor was found after extensive examination. Altogether, these results are in favor of an isolated nodal hidradenoma, for which we discuss two hypothesis: a primary nodal lesion, or a ‘benign metastasis’ of a cutaneous tumor. Cases of morphologically benign hidradenoma with lymph node involvement are exceptional. Our case, similar to every other reported case, was associated with an excellent prognosis, supporting the idea that these patients should not be overtreated.     

Intraepidermal Merkel cell carcinoma with no dermal involvement

Cutaneous Merkel cell carcinoma (MCC) typically involves the dermis. Less than 10% of MCC have epidermal involvement. Only one MCC confined exclusively to the epidermis has been previously reported but was not recognized until the lesion recurred with typical MCC in the dermis. We present a case of a wholly intraepidermal pagetoid MCC without dermal involvement in a 74-year-old man with a 2.0-cm solitary verrucous papule on the left index finger. The initial biopsy and complete excision specimens showed marked epidermal hyperplasia, focal prominent squamous cell atypia, and MCC with florid pagetoid spread through the epidermis. There was no evidence of tumor within the dermis. The pagetoid MCC tumor cells showed diffuse cytoplasmic staining with antibodies to cytokeratin 20, and negative staining for chromogranin, neurofilament, S-100, vimentin, HMB45, leukocyte common antigen, and CD3. The cell of origin of MCC is still debated. The existence of an entirely intraepidermal variant of MCC would lend support to the view that MCC is a neoplastic expression of Merkel cells in at least some cases. Dermal-based MCC is a high-grade primary cutaneous neoplasm, but MCC confined exclusively to the epidermis may have a better prognosis.     

Hidradenocarcinoma: a histological and immunohistochemical study

The diagnosis of hidradenocarcinoma is difficult due to a combination of factors including inconsistent nomenclature/ classification, rarity of the neoplasm, and variable morphology of cells composing the neoplasm. Immunohistochemistry has not been previously performed on a series of hidradenocarcinomas. We evaluated six cases of hidradenocarcinoma histologically and immunohistochemically using antibodies to gross cystic disease fluid protein-15 (GCDFP-15), carcino-embryonic antigen (CEA), epithelial membrane antigen (EMA), S-100 protein, keratin AE1/3, cytokeratin 5/6, p53, bcl-1, bcl-2, and Ki67. Histology suggested concurrent eccrine and apocrine differentiation of the cases. Ki67 and p53 staining was strongly positive in five of six tumors. The neoplasms stained with antibodies to CEA, S-100 protein, GCDFP-15, EMA, bcl-1, and bcl-2 in no consistent pattern. All tumors studied stained positively for keratin AE1/3 and cytokeratin 5/6. In making the diagnosis of hidradenocarcinoma, it may be unnecessary to separate hidradenocarcinoma into eccrine and apocrine categories, and although Ki67 and p53 may be helpful, histological parameters remain paramount.     

Squamous cell apocrine hidradenoma

Apocrine hidradenoma is a benign adnexal neoplasm with apocrine differentiation. The neoplasm is composed of four different types of epithelial cells, including pale or clear cells, polygonal cells, mucinous cells and squamous cells, with variable proportions of them from case to case. In most examples of this neoplasm, clear or the polygonal cells are predominant, whereas the other types of neoplastic cells are less abundant. We report two cases of apocrine hidradenoma mostly composed of squamous cells. Histopathologic examination showed that the neoplasms were composed of both solid and cystic areas. The solid aggregations of neoplastic cells were composed of a peripheral layer of basaloid polygonal cells, whereas squamous cells forming the bulk of the aggregations. These squamous cells showed large eosinophilic cytoplasm and vesicular nuclei with prominent nucleoli. In one case, small foci of mucinous cells could also be seen in some aggregations of neoplastic cells, mostly around ductal structures. In both the cases, some of the tubular structures lined by epithelial cells showed evidence of decapitation secretion in their luminal border. The neoplastic stroma consisted of sclerotic collagen bundles when compared with adjacent normal dermis, and artefactual clefts separated the neoplasms from the surrounding tissue. The rare cases described in this report are exceptional because most of the neoplastic cells showed squamous appearance and for that reason we think that squamous cell apocrine hidradenoma is the most appropriate name for these neoplasms.     

Pure mucinous (colloid) adenocarcinoma of the conjunctiva

Primary mucinous carcinomas of the periorbital region are very rare and often require differential diagnosis of metastatic disease. We describe a case of pure mucinous adenocarcinoma arising in the subconjunctival stroma of the ocular fornix in a female patient with a longstanding history of bilateral ocular cicatricial pemphigoid. Histologically, the tumor was composed of predominantly goblet‐like cells floating in pools of mucin separated by delicate collagenous septa. The initial suspicion was of primary cutaneous mucinous carcinoma and less likely endocrine mucin‐producing sweat gland carcinoma, however the CK7‐/synaptophysin‐/chromogranin‐immunoprofile did not confirm either of the two. Focal areas of the tumor demonstrated peripheral staining for p63 and CK5/6 suggestive of an in situ component. Additional studies showed that the tumor cells were positive for CK20, CDX2, villin and MUC2. Given the final immunophenotype of the tumor, metastatic lesion from the lower gastrointestinal tract had to be ruled out. Thorough clinicoradiological work‐up did not reveal any other primary tumors or evidence of metastatic disease elsewhere. Unique histomorphology, the presence of an in‐situ component and negative clinical investigation suggest that this is a primary mucinous adenocarcinoma arising in the ocular fornix. This case may represent the first report of this entity in the literature.     

Benign mucinous metaplasia of the penis. A lesion resembling extramammary Paget's disease

Benign mucinous metaplasia in the surface epithelium of the genital area is rare and has only been reported once in the vulva. A unique case of benign mucinous metaplasia of the prepuce in a 65-year-old man is reported here. The lesion measured 0.6 cm, was located in the mucous surface of the foreskin, and showed acid mucin containing cells. We regard benign mucinous metaplasia as a reactive rather than a neoplastic process. The main lesions to be considered in the differential diagnosis are mucinous syringometaplasia, extramammary Paget's disease, cutaneous squamous cell carcinoma in situ with mucinous metaplasia, superficial spreading malignant melanoma, and epidermotropic metastasis. The confinement of mucin-containing cells to the epidermis, the absence of nuclear atypia, the basal orientation of the nuclei, the predominant location of the cells in the upper layers of the epithelium, and the fact that the mucinous cells are replacing the squamous epithelium rather that infiltrating it, all assist in recognizing mucinous metaplasia of the penis as a specific and benign entity.     

黏蛋白痣10例临床病理分析

【摘要】 目的 探讨黏蛋白痣的临床病理特征。方法 回顾性分析2014年1月至2019年12月在中国医学科学院皮肤病医院经临床及组织病理确诊的10例黏蛋白痣患者的临床和病理资料。结果 10例黏蛋白痣均为儿童期发病,平均发病年龄6.5岁。7例皮损位于躯干,其中4例位于背部;2例位于四肢,1例躯干、四肢泛发。皮损在局部排列成线状、带状或簇集状,质地柔软至坚硬不等,颜色呈肤色、淡红色和黄色。组织病理检查：10例均表现为真皮内胶原纤维束排列紊乱,其间可见程度不等的黏蛋白沉积,沉积的位置和程度不一,6例在沉积区见胶原纤维增粗、红染,其余4例表现为胶原稀疏、减少;2例出现基底层灶状液化变性,3例出现真皮内不等量成熟脂肪组织等。结论 黏蛋白痣的病理主要表现为真皮内程度不等的黏蛋白沉积于杂乱的胶原束间,可与一些其他疾病类似,容易误诊,临床和病理紧密联系可确诊。     

Cytokeratin 10-negative nested pattern enables sure distinction of clonal seborrheic keratosis from pagetoid Bowen's disease

Background: The histopathologic pattern of clonal seborrheic keratosis (SK) is quite similar to the nested pattern of pagetoid Bowen's disease [squamous cell carcinoma in situ (SCCIS)], and differentiation between the two can be challenging, especially when only small pieces are available for interpretation. Methods: Eleven examples of clonal SK and 13 examples of pagetoid SCCIS were examined histopathologically (tabulating necrotic keratinocytes, suprabasal mitoses, infiltrate, parakeratosis housing plump nuclei, crowding of nuclei) and immunohistochemically (using Ki‐67, bcl‐2, cytokeratin 7 and cytokeratin 10). Sensitivity, specificity, p‐values (Fisher's exact test, two‐tailed) and positive/negative likelihood ratios (+LR/?LR) were calculated. Results: Significant differences were seen with regard to crowding (p = 0.0009) and mitoses (p = 0.0006); however, only complete absence of necrotic keratinocytes or of crowding appeared to be diagnostically convincing for a diagnosis of clonal SK (?LR < 0.01). Significant differences were also seen with bcl‐2 (p = 0.0005) and cytokeratin 10 antibodies (p < 0.00001). Both markers displayed a typical nested pattern in clonal SK, nests being bcl‐2‐positive and cytokeratin 10‐negative. Cytokeratin 10‐negative nests were the most convincing criterion for differentiation between clonal SK and pagetoid SCCIS (+LR > 10, ?LR < 0.01). Conclusions: The most reliable marker to distinguish clonal SK from pagetoid SCCIS is cytokeratin 10 when it spares nests. Other criteria that assist in the differential diagnosis are bcl‐2 expression, absence of crowding and of mitoses. Böer‐Auer A, Jones M, Lyasnichaya OV. Cytokeratin 10‐negative nested pattern enables sure distinction of clonal seborrheic keratosis from pagetoid Bowen's disease.     

Syringometaplasia: Mucinous and Squamous Variants

The eccrine sweat ducts are normally lined by cuboidal epithelial cells which may rarely undergo metaplasia, i.e. syringometaplasia. Two lesions were observed in which eccrine sweat ducts displayed the mucinous and squamous variants of syringometaplasia. The first lesion clinically and histologically appeared to be a plantar wart. Microscopically, it consisted of a central invagination surrounded by marked epidermal acanthosis and hyperkeratosis. The invagination was lined by keratinocytes admixed with mucin-filled goblet cells. The mucin was positive by the Alcian blue (pH 2.5) and mucicarmine stains. Numerous eccrine sweat ducts led into the invagination and were focally lined by the mucin-laden cells. Recognition of mucinous syringometaplasia is important since it may be confused with primary or metastatic adenocarcinoma of the skin. The second lesion occurred on the outer ear and was clinically believed to be chondrodermatitis nodularis helicis. Microscopically, there were many islands of atypical squamous cells within the papillary and reticular dermis. These epithelial islands represented squamous syringometaplasia since many contained central lumina with eosinophilic cuticles and blended with normal ductal structures. It is important not to confuse this metaplastic change with invasive squamous cell carcinoma. Squamous syringometaplasia may be analogous to necrotizing sialometaplasia, a recently described phenomenon which occurs in minor salivary glands.     

Cutaneous mucinosis of infancy: is it a real entity or the paediatric form of lichen myxoedematosus (papular mucinosis)?

We describe a girl presenting with a childhood dermal mucinosis in which we had the unique opportunity to find all the transitional histological features of lichen myxoedematosus (papular mucinosis), from its early focal mucin deposition in the reticular dermis to its late findings of interstitial mucin deposition, dermal fibrosis and fibroblast proliferation. Her father reported having had similar lesions when he was a child, which completely disappeared during adolescence. This case, and a re-evaluation of the literature, suggests that cases of cutaneous mucinosis of infancy that are not hamartomatous conditions such as mucinous naevi are in fact the infantile presentation of lichen myxoedematosus (papular mucinosis) and, in addition to other cases in the literature, suggests a genetic and familial factor in lichen myxoedematosus (papular mucinosis).     

Reversed cellular polarity in primary cutaneous mucinous carcinoma: A study on tight junction protein expression in sweat gland tumors

Primary cutaneous mucinous carcinoma (PCMC) is a rare sweat gland tumor characterized by the presence of abundant mucin around the tumor islands, but the molecular mechanisms for this structure are not well elucidated. Because mucin is epithelial in nature, it is likely to be produced by epithelial tumor cells, not by surrounding stromal cells. We hypothesized that the abundant mucin is a result of reversed cellular polarity of the tumor. To test this hypothesis, we conducted an immunohistological study to investigate expression of tight junction (TJ) proteins occludin and ZO‐1 in PCMC, as well as in normal sweat glands and other sweat gland tumors. Dot‐like or linear expression of TJ proteins was observed at ductal structures of sweat glands, and ductal or cystic structures of related tumors. In PCMC, however, TJ protein expression was clearly visible at the edges of tumor cell islands. This study provides evidence to show that the characteristic histological structure of PCMC is caused by inverse polarization of the tumor cells, and that TJ proteins are useful markers of ductal differentiation in sweat gland tumors.     

Concomitant neoplasms in the skin and stomach unveil the role of type IV collagen and E‐cadherin in mucin core protein 5AC expression in vivo

Mucin core protein (MUC) 5AC is a gel‐forming glycoprotein that is expressed in different types of tumour cells. MUC5AC expression in cultured cells is regulated through the extracellular matrix and through remodelling by other membranous proteins such as type IV collagen (COL4) and E‐cadherin. However, it has not been elucidated whether COL4 and E‐cadherin affect MUC5AC expression in tumours in vivo. Here, by analysing a single individual with concomitant neoplasms in the skin [extramammary Paget disease (EMPD)] and the stomach (gastric cancer), we show that MUC5AC expression is reduced in COL4 and membranous E‐cadherin‐expressing EMPD specimens whereas MUC5AC is not abolished in gastric cancer with COL4 negativity and E‐cadherin cytoplasmic localization. As the EMPD and gastric cancer specimens were derived from a single patient, each specimen had the same genetic background. These in vivo results support previous in vitro studies which showed that COL4 and E‐cadherin downregulated MUC5AC expression. Our study suggests that concomitant neoplasms in different organs of the same individual can serve as a strong tool for uncovering functional diversity in tumour markers in distinct cancer cells.     

Schweißdrüsenkarzinome der Haut

Sweat gland carcinomas are rare malignant tumors of the skin. The well-defined entities porocarcinoma, microcystic adnexal carcinoma, aggressive digital papillary adenocarcinoma, mucinous eccrine carcinoma, adenoid cystic carcinoma, spiradenocarcinoma, cylindrocarcinoma, hidradenocarcinoma are described. The article summarizes essential clinical, prognostic and histopathological findings of these tumors and takes in focus special recommendations for dermatologists and surgeons to plan biopsies and operations.     

Syringocystadenocarcinoma Papilliferum in Situ: A Case Report and Review of the Literature

Syringocystadenocarcinoma papilliferum is an exceedingly rare malignant neoplasm of the apocrine glands. There are only about half a dozen cases reported in the literature with one case being an in situ lesion. A 32‐year‐old Nigerian female presented with a 1‐cm, hyperpigmented, slow‐growing verrucous nodule located on her mid‐posterior neck. The lesion had been present since birth. Histopathological examination revealed bilocular cystic cavities with papillary projections lined by double layers of epithelium. The luminal layer was composed of columnar cells with decapitation‐type secretion. The fibrovascular stroma within the papillary projections contains numerous plasma cells with some lymphoid cells. The cystic cavities showed close apposition to the epidermis of the skin with focal, keratinizing squamous epithelium lining that was contiguous to the infundibular epithelium in foci. Necrosis en masse was present within the tumor. There were focal areas of solid aggregates of tumor cells with crowded, pleomorphic, and hyperchromatic nuclei. Many mitoses, some of them atypical, were identified. The tumor was confined within the cystic cavities with no dermal invasion. A diagnosis of syringocystadenocarcinoma papilliferum in situ was made.     

Adenosquamous carcinoma of the skin--ultrastructural and immunohistochemical studies

Adenosquamous carcinoma, which arose on the face of a 83-year-old woman was studied ultrastructurally and immunohistochemically. The tumor was composed of squamoid cells and mucinous cells including signet-ring cells. Electron microscopically, the tumor cells developed numerous microvilli on the cell surface, and had tonofilaments, well-developed rough endoplasmic reticulum and secretory granules of a mucinous type in the cytoplasm. The signet-ring cells had a large intracytoplasmic cavity containing fine fibrillar, mucin-like substance. Occasionally observed were intercellular masses, around which the tumor cells formed hemidesmosome-like and basal lamina-like structures. Immunohistochemical staining revealed foci of positive reaction for laminin surrounding the tumor cells. The tumor cells displayed positive stainings for stratified-epithelial keratins, but not for simple-epithelial keratins. From these findings, it was concluded that the present tumor might be a carcinoma of squamous cell origin, showing a mucinous metaplasia.