Low-Grade Hidradenocarcinoma of the Foot With Metastasis to a Lymph Node.

ABSTRACT: Hidradenocarcinoma (HAC) is a rare adnexal tumor associated with the potential for locoregional recurrence and systemic metastasis. The clinical appearance of HAC is nonspecific, frequently presenting as a solitary firm subcutaneous nodule or plaque on the head and neck region or distal extremities. These tumors show histomorphologic heterogeneity, as they can be low and high grade. Distinguishing HAC from hidradenoma, especially the low-grade variant of HAC, can be challenging as both tumors can show histologic overlapping features. In this article, we describe a case of a 33-year-old patient presenting with a low-grade HAC of the plantar foot who was subsequently found to have lymph node metastasis.

Whole-Exome Sequencing of a Case of Squamoid Eccrine Ductal Carcinoma Reveal Similarities With Cutaneous Squamous Cell Carcinoma.

ABSTRACT: Squamoid eccrine ductal carcinoma (SEDC) is a poorly documented but likely underrecognized sweat gland malignancy with significant risk for local recurrence and potential for metastasis and rare disease-related mortality. Histopathologically, the tumor demonstrates a biphasic differentiation pattern: superficially, the tumor has squamous differentiation [indistinguishable from well-differentiated cutaneous squamous cell carcinoma (cSCC)], while the deeper aspect has a more infiltrative pattern with prominent ductal differentiation. Diagnosis of SEDC relies upon histopathologic examination alone. Its pathogenesis is poorly understood, and its genomic features have yet to be described. In this article, we characterize the genomic features in a case of SEDC through whole-exome sequencing, then compare its features with cSCC and other eccrine ductal carcinomas. Whole-exome sequencing revealed 30 mutations/Mb with 21 pathogenic or likely pathogenic mutations in total, identified across 14 different genes. The genomic abnormalities identified in this case of SEDC overlap considerably with those found in cSCC but not those of other sweat gland malignancies. The clinical and histopathologic features of SEDC previously reported and the genetic features determined from this case suggest that this tumor may arise initially as a well-differentiated cSCC that subsequently undergoes divergent differentiation focally to resemble a sweat gland malignancy. Genetic analyses of additional cases are warranted to clarify this consideration.

CDX2 and SATB2 positivity in pilomatrix carcinoma: Avoiding an erroneous diagnosis of cutaneous metastasis of gastrointestinal origin.

An 80-year-old female presented with a slowly growing 2-cm nodule on her shoulder over a 1-year period. Histopathologic sections of a biopsy specimen showed a multinodular, dermal-based basaloid tumor with areas of clear-cell change, stromal induction, as well as significant cytologic atypia and atypical mitotic activity. An initial investigation revealed positive staining of CDX2, a well-known marker of tumors of gastrointestinal origin. The case was referred to our dermatopathology service for consultation to determine if the lesion was in keeping with a cutaneous metastasis. On receipt of the case, an extended immunohistochemical panel was performed including SATB2, which displayed a similar pattern of staining as seen with CDX2. Although pathologists are most familiar with CDX2 and SATB2 as markers of gastrointestinal origin, the recent dermatopathology literature highlights that primary adnexal lesions of the skin also display positivity for CDX2 and can exhibit SATB2 positivity. We share a case of pilomatrix carcinoma with positive expression of nuclear CDX2 and SATB2, adding to the recent literature to (a) increase recognition of this staining pattern in hair follicle tumors, and (b) discuss briefly the shared molecular underpinnings in the tumorigenesis of gastrointestinal tumors and tumors of hair follicle origin that help clarify this underrecognized immunohistochemical pattern.

Skin adnexal carcinoma with BRD3-NUTM2B fusion.

NUT carcinomas are genetically defined epithelial neoplasms. Most tumors harbor fusions of NUTM1 with BRD4 or BRD3. Their histopathologic features have been predominantly reported as undifferentiated or poorly differentiated squamous cell carcinoma, and clinically they tend to be aggressive cancers. However, recent studies have revealed a broader spectrum of NUTM1-rearranged neoplasms with several new fusion partners and associated variable histopathologic phenotypes and clinical behaviors, including benign and malignant cutaneous poroid tumors. We report herein a primary invasive carcinoma of skin adnexal origin with a previously undescribed fusion between BRD3 and NUTM2B. The tumor occurred on the shoulder of a 7-year-old girl and was excised with negative margins. A sentinel lymph node was positive. After follow-up of 23 months, and without systemic treatment, the child remains free of tumor. This case expands the spectrum of NUT carcinomas by including a skin adnexal variant with follicular infundibular differentiation, a novel genomic aberration, and preliminary evidence of a less aggressive clinical course.

Independent primary cutaneous and mammary apocrine carcinomas with neuroendocrine differentiation: Report of a case and literature review.

Cutaneous apocrine carcinomas share common features with their counterparts in the breast; hence, metastatic mammary carcinoma must be excluded before such lesions can be designated primary cutaneous neoplasms. Primary tumors from either source rarely exhibit neuroendocrine differentiation. We report a case of a 72-year-old female with a painless 1.2-cm scalp nodule. An incisional biopsy revealed dermal involvement by an invasive apocrine carcinoma juxtaposed to a benign apocrine cystic lesion. Immunohistochemically, the carcinoma expressed neuroendocrine proteins including synaptophysin, chromogranin, and CD56. A primary cutaneous apocrine carcinoma with neuroendocrine differentiation was favored, but additional investigations to exclude breast origin were recommended. These revealed a 1.1-cm nodule in the right breast, which proved to be an invasive ductal carcinoma, morphologically and immunophenotypically similar to the scalp lesion. This confounded the case, yet factors militating against metastatic breast carcinoma to skin included (a) the small size of the mammary tumor, (b) absence of other metastatic disease, and (c) juxtaposition of the scalp carcinoma to a putative benign precursor. Molecular studies were undertaken to resolve the diagnostic quandary. Single nucleotide polymorphism microarray analysis revealed distinct patterns of chromosomal copy number alterations in the two tumors, supporting the concept of synchronous and unusual primary neoplasms.

Vulvar apocrine hidradenocarcinoma arising in a hidradenoma papilliferum-A case report.

Hidradenoma papilliferum (HP) is a benign adnexal neoplasm of the vulva that typically presents as a unilateral, flesh-colored papule in the labium majus in middle-aged Caucasian women. It is considered to be a close counterpart of the intraductal papilloma of the breast. Malignant transformation is rare with few reports in the literature. We present a case of vulvar mammary-type apocrine hidradenocarcinoma arising in an HP.

A clinical, pathological and immunohistochemical series of 9 cases of primary cutaneous apocrine carcinomas of the head and neck.

BACKGROUND/OBJECTIVES: Primary cutaneous apocrine carcinoma is a rare malignant adnexal skin tumour that can recur locally, spread to regional lymph nodes and metastatize to visceral organs. Wide dissemination and death from disease are much less common. The axilla is the most common site of presentation. It is infrequently reported in the head and neck region. METHODS: All cases diagnosed as primary cutaneous apocrine carcinoma of the head and neck were retrospectively collected from the archives of the Division of Pathological Anatomy, University of Florence from 1996 to 2016. There was no history or clinical evidence of breast cancer. Clinical data and follow-up were collected by the clinicians. RESULTS: Nine cases were found, with a mean age of 76 years, ranging in size between 0.3 and 3.5 cm. Clinically, they were frequently mistaken for basal cell carcinomas. Histopathologically, all the tumours showed decapitation secretion, a tubular, solid or mixed (tubulo-papillary and solid-tubular) growth pattern and were predominantly classified as grade 2 tumours. GCDFP-15 and hormone receptors were variably expressed. HER2 and podoplanin were negative in all cases. In one case, spreading to regional lymph nodes was observed. No cases were associated with death due to the disease. CONCLUSION: As immunohistochemical analysis lacks specificity in distinguishing primary cutaneous apocrine carcinoma from a cutaneous metastasis of breast carcinoma, detailed clinical history, breast examination, adequate treatment and follow-up are necessary to confirm a diagnosis of primary cutaneous apocrine carcinoma.

Matrical carcinoma with melanocytic hyperplasia mimicking nodular melanoma in an elderly Mexican male.

Matrical carcinoma with melanocytic hyperplasia (MCMH), previously referred to as malignant melanocytic matricoma, is a rare variant of the uncommon pilomatrical carcinoma, occurring most often on the head/neck and upper backs of middle-aged men. Nodular lesions may resemble pigmented basal cell carcinoma or melanoma clinically. We present a case of MCMH in a Hispanic patient with history of melanoma. Histopathological clues to appropriate diagnosis include basaloid cells, numerous atypical mitotic figures, matrical differentiation, shadow cells, strong diffuse nuclear and cytoplasmic expression of ß-catenin, and interspersed pigmented dendritic melanocytes.

Squamoid Eccrine Ductal Carcinoma: An Aggressive Mimicker of Squamous Cell Carcinoma.

Squamoid eccrine ductal carcinoma (SEDC) is an uncommon cutaneous adnexal malignancy that has the potential for an aggressive clinical course. The authors present a case of SEDC that resulted in widespread metastases and death. The clinical, histological, and immunohistochemical features of SEDC and several entities on the differential diagnosis are reviewed.

Microcystic adnexal carcinoma with sebaceous differentiation: Three cases.

Microcystic adnexal carcinoma (MAC) is a low-grade malignant tumor of the skin. Histologically, this tumor shows a biphasic pattern, with cords and nests of basaloid cells, as well as keratin horn cysts. This biphasic histological appearance has been interpreted by some authors as a sign of double eccrine and folliculosebaceous-apocrine differentiation, whereas some other authors defend a solely eccrine differentiation. In this context, sebaceous differentiation in MAC would support the first option. However, there are only 3 cases of MAC with sebaceous differentiation in the literature, and all of them were reported before adipophilin was available, which in the appropriate context (eg, testing clear cells for sebaceous vs eccrine differentiation) is very useful. In this study, we present 3 cases of MAC with focal sebaceous differentiation confirmed by immunoexpression of adipophilin in the sebaceous foci.

p63 and smooth muscle actin expression in low-grade spiradenocarcinomas in a case of CYLD cutaneous syndrome.

Low-grade spiradenocarcinoma is a rare skin tumor, with fewer than six reported cases, arising in the context of CYLD cutaneous syndrome (CCS; syn: Brooke-Spiegler syndrome [BSS]). We report two independent cases of spiradenocarcinoma arising in a 50-year-old man with CCS. The tumors grew rapidly, prompting clinical excision. The histologic features in our cases corresponded to the salivary gland type basal cell adenocarcinoma-like pattern, low grade (BCAC-LG), that has been previously recognized as a recurrent finding in CCS. We performed genetic testing of the patient and found a novel mutation in CYLD. Recognition of low-grade spiradenocarcinoma can be difficult for the pathologist as the features can be subtle, especially in those cases where the transition from benign to malignant tumor is gradual. We examined p63 and smooth muscle actin (SMA) expression patterns in BCAC-LG and compared it with the expression pattern in the precursor spiradenoma. Our report provides information on two rare tumors in the context of CCS and suggests that the pattern of p63 and SMA staining may aid pathological detection of the BCAC-LG subtype of spiradenocarcinoma.

Loss of the tumor suppressor CYLD enhances Wnt/beta-catenin signaling through K63-linked ubiquitination of Dvl.

The mechanism by which Wnt receptors transduce signals to activate downstream beta-catenin-mediated target gene transcription remains incompletely understood but involves Frizzled (Fz) receptor-mediated plasma membrane recruitment and activation of the cytoplasmic effector Dishevelled (Dvl). Here, we identify the deubiquitinating enzyme CYLD, the familial cylindromatosis tumor suppressor gene, as a negative regulator of proximal events in Wnt/beta-catenin signaling. Depletion of CYLD from cultured cells markedly enhances Wnt-induced accumulation of beta-catenin and target gene activation. Moreover, we demonstrate hyperactive Wnt signaling in human cylindroma skin tumors that arise from mutations in CYLD. At the molecular level, CYLD interacts with and regulates K63-linked ubiquitination of Dvl. Enhanced ubiquitination of the polymerization-prone DIX domain in CYLD-deficient cells positively links to the signaling activity of Dvl. Together, our results argue that loss of CYLD instigates tumor growth in human cylindromatosis through a mechanism in which hyperubiquitination of polymerized Dvl drives enhancement of Wnt responses.

Polymorphous Sweat Gland Carcinoma: An Immunohistochemical and Molecular Study.

Polymorphous sweat gland carcinoma is an uncommon low-grade malignant adnexal tumor with a marked predilection for the distal extremities. Histologically, the lesions are characterized by a cellular proliferation showing a combination of growth patterns, including trabecular, solid, tubular, cribriform, or adenoid cystic and pseudopapillary. The immunohistochemical and molecular profile of these tumors has not yet been properly addressed. We have studied 3 cases of polymorphous sweat gland carcinoma using a broad panel of immunohistochemical markers including cytokeratin AE1/AE3, CK5/6, MOC31, p40, p63, p16, chromogranin, synaptophysin, CD56, MIB-1, estrogen receptor, progesterone receptor, androgen receptor, BER-EP4, smooth muscle actin, epithelial membrane antigen, carcinoembryonic antigen, CD117, S100 protein, HBME-1, DOG1, vimentin, and mammaglobin. We also examined for the MYB-NFIB fusion by fluorescent in situ hybridization (ISH) and for human papilloma virus by ISH. Our studies show that cytokeratin AE1/AE3, CK5/6, p40, p63, p16, chromogranin, and CD56 stains were positive in all 3 cases. All 3 cases were negative for MYB-NFIB fusion by fluorescent ISH which rules out adenoid cystic carcinoma. DNA ISH studies for high-risk human papilloma virus were negative in all cases. MIB-1 proliferation index was very high (30%-70% nuclear positivity), supporting a malignant phenotype. The positivity for chromogranin and CD56 suggests partial neuroendocrine differentiation. The differential diagnosis includes metastases from internal malignancies, basal cell carcinoma, and other benign and malignant adnexal neoplasms such as adenoid cystic carcinoma, ductal eccrine carcinoma, and microcystic carcinoma. Positivity for p16 in combination with chromogranin and CD56 may be potentially good markers for differentiating this tumor from other adnexal tumors.

Utility of Immunohistochemistry in Distinguishing Primary Adnexal Carcinoma From Metastatic Breast Carcinoma to Skin and Squamous Cell Carcinoma.

The distinction between primary adnexal carcinoma (PAC) from metastatic breast carcinoma (BrCa) to skin and squamous cell carcinoma (SCC), particularly those with ductal differentiation (SCCDD), can be quite challenging, despite adequate history. The aim of the study was to determine the utility of an immunohistochemistry (IHC) panel to differentiate these entities and apply them to ambiguous tumors. Twenty-seven PAC, 7 metastatic BrCa, 28 SCC, and 16 ambiguous cases (SCCDD vs. PAC, n = 13 and metastatic BrCa vs. PAC, n = 3) were analyzed using CD23, PAX5, D2-40, P63, and CD117 immunohistochemistry. A total of 9 (33%) PAC were CD117 positive, whereas all metastatic BrCa and SCC were negative (P = 0.0002). D2-40 was expressed in 16 (59%) PAC and 16 (57%) SCC cases, but none of the metastatic BrCa cases (P = 0.0041). Of the 13 ambiguous tumors with a differential diagnosis of SCCDD versus PAC, all were positive for P63, 10 were positive for D2-40, and 1 was positive for CD117. Of the 3 ambiguous tumors with a differential diagnosis of PAC versus metastatic BrCA, 2 were positive for CD117, whereas none showed reactivity for D2-40 or P63. All cases were negative for CD23 and PAX5. Our study indicates that CD117 reactivity favors a PAC with a sensitivity and specificity of 33% and 100%, respectively. D2-40 and P63 expression highlighted both PAC and SCC and seems to be useful in excluding metastatic BrCa with a sensitivity and specificity of 58% and 100%, and 98% and 100%, respectively. Despite previous reports, CD23 and PAX5 do not seem to be useful.

[Microcystic adnexal carcinoma: A case report]. / Carcinome annexiel microkystique : à propos d'une observation.

We report a case of microcystic adnexal carcinoma in a 80-year-old woman. This is a rare malignant adnexal cutaneous tumor with glandular and follicular differentiation, rare, often asymptomatic, with late diagnosis and slow growth, locally aggressive and rarely metastatic. The distinction with other benign and malignant skin tumors is difficult.

Melanocytic Matrical Carcinoma Mimicking Melanoma.

Melanocytic matrical carcinoma is a very uncommon malignant neoplasm with follicular differentiation. The lesion often presents as a solitary nodule on sun-exposed skin of elderly patients. Histopathologically, it is characterized by proliferation of atypical matrical cells admixed with an increased number of melanocytes, and some atypical matrical cells may have cytoplasmic pigment. When melanocytic proliferation or melanin pigment is prominent, melanocytic metrical carcinoma can mimic melanoma. Here, we present a novel case of melanocytic matrical carcinoma mimicking melanoma in an 80-year-old man with our findings in histopathologic and immunohistochemical study.

An Aggressive Microcystic Adnexal Carcinoma Infiltrating the Sternum.

Microcystic adnexal carcinoma is a rare cutaneous tumor that is often misdiagnosed and has the potential to be aggressive. Mohs surgery is the treatment of choice to prevent recurrences. We present a case of a large recurrent microcystic adnexal carcinoma on the sternum, initially diagnosed as a basal cell carcinoma. This tumor infiltrated the muscle and bone and was unresectable with Mohs surgery.

J Drugs Dermatol. 2017;16(2):180-181.

[Why is it important to differentiate trichoblastic carcinomas (CT) from basal cell carcinomas (CBC). About 21 cases]. / De l'intérêt de différencier les carcinomes trichoblastiques (CT) des carcinomes basocellulaires (CBC). À propos de 21 cas.

Trichoblastic carcinoma is a rare epithelial malignant epithelial tumor, its diagnosis is difficult and the therapeutic management is non-consensual. This retrospective study, carried out between 2009 and 2015, covered 21 cases and analyzed the diagnostic and therapeutic characteristics of trichoblastic carcinomas. Sex ratio is 2. Trichoblastic carcinoma predominated in the face (65% of cases), particularly in perinasal (30% of cases). Its clinical presentation is in 95% of cases as basal cell carcinoma, which is the first clinical diagnosis evoked. The average size of the tumors was 2.3cm in diameter (from 0.7cm to 15cm). The treatment of these tumors is surgical: the margins retained were on average 0.7cm (0.5cm to 1cm). The first excision was mostly performed under local anesthesia, healthy borders were found in less than 40% of cases, requiring another intervention under general anesthesia with reconstruction by flap or skin graft in nearly 80% of cases. The lymph node metastasis rate was 5%. Three cases of recurrence (17%) occurred between 18 months and 6 years follow-up, despite complete resection. One case recurred three times. These results highlight the difficulty of diagnosing trichoblastic carcinomas, often confused with basal cell carcinomas. Though larger, poorly limited and infiltrating, trichoblastic carcinomas are not really distinguished from basal cell carcinomas. Only the anatomopathological examination of the excision piece make it possible to conclude, the biopsy being most often insufficient. Their local aggressiveness requires a greater margin of excision. The micrographic analysis of Mohs, for the periorificial lesions of the face, would reduce margins, increase their reliability and limit the number of surgical revisions. Finally, the literature reports a high rate of ganglion and visceral metastases (between 9.5 and 11%). Initial search for distal lymph node or metastatic involvement is essential, as well as regular clinical follow-up.

Papillary adnexal neoplasm (aggressive digital papillary adenocarcinoma) on the ankle of a 15-year-old girl: case report and review of literature from a pediatric perspective.

Digital papillary adenocarcinoma is a rare malignant tumor of the sweat glands, most commonly encountered in adult males. Only few pediatric cases have been reported, with an apparent predominance of females and none on the ankle. We report a case of a 15-year-old girl with a slowly growing, non-tender mass on the right ankle presenting with difficulty in walking; clinically believed to be a keloid. Excision of the mass revealed a glandular neoplasm with largely eccrine and focally apocrine differentiation. Histologic features do not reliably predict biologic behavior. Because of the existing confusion over the nomenclature, we propose that such tumors be called 'papillary adnexal neoplasms of distal extremities'.