Wnt/ß-Catenin-Activated Nonpilomatrical Carcinoma of the Skin: A Case Series.

Among skin epithelial tumors, recurrent mutations in the APC/CTNNB1 genes resulting in activation of the Wnt/ß-catenin pathway have been reported predominantly in neoplasms with matrical differentiation. In the present study, we describe the morphologic, immunohistochemical, and genetic features of 16 primary cutaneous carcinomas harboring mutations activating the Wnt/ß-catenin pathway without evidence of matrical differentiation, as well as 4 combined tumors in which a similar Wnt/ß-catenin-activated carcinoma component was associated with Merkel cell carcinoma (MCC) or pilomatrical carcinoma. Among the pure tumor cases, 6 of 16 patients were women with a median age of 80 years (range, 58-98 years). Tumors were located on the head and neck (n = 7, 44%), upper limb (n = 4, 25%), trunk (n = 3, 18%), and leg (n = 2, 13%). Metastatic spread was observed in 4 cases resulting in death from disease in 1 patient. Microscopically, all cases were poorly differentiated neoplasms infiltrating the dermis and/or subcutaneous tissue. In 13 cases, solid "squamoid" areas were associated with a basophilic component characterized by rosette/pseudoglandular formation resulting in a biphasic appearance. Three specimens consisted only of poorly differentiated carcinoma lacking rosette formation. Immunohistochemical studies showed frequent expression of EMA (100%), BerEP4 (100%), cytokeratin 7 (94%), chromogranin A (44%), synaptophysin (82%), and cytokeratin 20 (69%). Complete loss of Rb expression was observed in all but 1 case. Nuclear ß-catenin and CDX2 expressions were detected in all cases. Recurrent pathogenic somatic mutations were observed in APC (60%), CTNNB1 (40%), and RB1 (n = 47%). Global methylation analysis confirmed that cases with rosette formation constituted a homogeneous tumor group distinct from established skin tumor entities (pilomatrical carcinoma, MCC, and squamous cell carcinoma), although the 3 other cases lacking such morphologic features did not. In addition, we identified 4 combined neoplasms in which there was a component showing a similar poorly differentiated rosette-forming carcinoma demonstrating Rb loss and ß-catenin activation associated with either MCC (n = 3) or pilomatrical carcinoma (n = 1). In conclusion, we describe a distinctive neoplasm, for which we propose the term "Wnt/ß-catenin-activated rosette-forming carcinoma," morphologically characterized by the association of rosette formation, squamous and/or neuroendocrine differentiation, diffuse CDX2 expression, Rb loss, and mutations in CTNNB1/APC genes.

A Combined Spindle Cell Melanoma and Sarcomatoid Squamous Cell Carcinoma: A Rather Unique Squamomelanocytic Tumor.

ABSTRACT: Squamomelanocytic tumor is a poorly defined term that indicates co-occurrence of malignant melanoma and squamous cell carcinoma within the same lesion. We present an unusual case of squamomelanocytic tumor in which both intermingling components showed predominantly spindle cell morphology and were confirmed with double staining for SOX-10 and AE1/AE3.

Utility of PRAME Immunohistochemistry in the Detection of Subtle Melanoma Microsatellites.

ABSTRACT: Microsatellitosis is well established as a prognostic factor in malignant melanoma. Its identification leads to subsequent upstaging with implications for further management. We describe 6 cases in which immunohistochemical staining for PReferentially expressed Antigen in MElanoma facilitated detection of small foci of micrometastasis on scanning magnification, which may be potentially missed in routine sections.

Poikilodermatous plaque-like hemangioma: Case series of a newly defined entity.

BACKGROUND: We present a distinctive type of acquired vascular proliferation, for which we propose the name of poikilodermatous plaque-like hemangioma. OBJECTIVE: The aim of this study was to summarize the clinical and histopathologic features in a case series of poikilodermatous plaque-like hemangioma. METHODS: Sixteen cases were identified from the routine clinical and referral practices of the authors. Clinical characteristics, including demographic details and clinical morphology, were collated. The salient histopathologic features, including immunohistochemical staining results, were summarized. RESULTS: The lesions were usually solitary erythematous-to-violaceous poikilodermatous plaques on the lower extremities and pelvic girdle, with an indolent clinical course. Mean age of affected patients was 72 (range 58-80) years, and there was a male predominance. Histology comprised a distinctive band-like proliferation of vascular channels suggestive of postcapillary venules within the superficial dermis with a background of fibrosis, edema, and loss of elastic fibers. Despite the clinical atrophic appearance, acanthosis was a frequent finding. LIMITATIONS: Retrospective study. CONCLUSION: Poikilodermatous plaque-like hemangioma is a distinctive and previously undescribed vascular proliferation defined by a constellation of consistent and reproducible clinical and histologic features.

CD34 and BerEP4 Are Helpful to Distinguish Basaloid Tricholemmoma From Basal Cell Carcinoma.

Tricholemmoma, a benign follicular neoplasm with outer root sheath differentiation, typically comprises clear or pale cells, and when multiple is pathognomic of Cowden's syndrome. The tumor is probably underrecognized and in basaloid examples can be difficult to distinguish from basal cell carcinoma (BCC). We studied 55 tricholemmomas (including 15 basaloid cases) and compared immunohistochemical profile with nodular BCC from our archives. Basaloid and non-basaloid tricholemmomas had similar staining characteristics. BerEP4 was focally positive (range 10%-20%) in only 3/39 (7.7%) tricholemmomas compared with widespread positivity in BCC (90.8%, 139 of 151 cases with ≥50% tumor area stained). CD34 was expressed, usually focally (median 20%, range 10%-90%), in 52/53 (98.1%) tricholemmomas and was negative in all 21 BCCs stained. EMA staining lacked sensitivity or specificity in differentiating tricholemmoma from BCC. Five or more Merkel cells were found in 7/17 (40.1%) tricholemmomas and 1/23 (4.3%) nodular BCCs studied. In summary, immunohistochemistry is helpful in distinction between tricholemmoma, including difficult basaloid examples (BerEP4 negative or focal, CD34 positive) compared with BCC (BerEP4 widespread in most cases, CD34 negative). The presence of 5 or more Merkel cells is a relatively specific but not a particularly sensitive discriminator.

Germline BRCA1-associated protein 1 mutation presenting as BAP1 inactivated melanocytic nevi in a child of a father with fatal paraganglioma.

BRCA1-associated protein 1(BAP1) inactivated melanocytic nevi are pink to tan and dome-shaped in clinical appearance, resembling dermal nevi, but with distinct histologic features of two melanocytic subpopulations: larger atypical melanocytes and nests of smaller, blander nevoid melanocytes. Pedigrees with BAP1 mutations are at greater risk of various malignancies. We report the case of a 16-year-old boy with multiple benign-appearing nevi, all demonstrating loss of BAP1 on immunohistochemistry. History revealed that his father had died of paraganglioma, which is also associated with BAP1 mutations.

Indolent CD8-positive lymphoid proliferation of acral sites: three further cases of a rare entity and an update on a unique patient.

BACKGROUND: Primary cutaneous indolent CD8-positive lymphoid proliferation is an emerging entity characterized by slowly enlarging papules and nodules that are pathologically comprised of clonal nonepidermotropic medium-sized atypical CD8(+) T-cells. Although the majority of lesions are solitary and located on the ears, bilateral symmetrical presentations have been described and lesions may arise at other peripheral or 'acral' sites. Patients follow a benign clinical course and systemic involvement has not yet been observed. Despite this, some medical practitioners classify such lesions as peripheral T-cell lymphoma, NOS, a category implying aggressive disease. OBJECTIVES: We present three cases seen in our institutions and provide an update on a previously reported unique patient who continues to develop recurrent and multifocal skin lesions. RESULTS: Systemic disease progression has not been observed, even in the presence of recurrent and multifocal cutaneous disease. CONCLUSIONS: Indolent CD8-positive lymphoid proliferation of acral sites is a distinctive and readily identifiable entity and should be included in the next consensus revision of cutaneous lymphoma classification. Although cases described thus far have followed an indolent clinical course, dermatologists should remain guarded about the prognosis and full staging and longitudinal observation are recommended until this condition is better understood.

Hereditary vitamin D-resistant rickets presenting as alopecia.

Hereditary vitamin D-resistant rickets (HVDRR) is a rare autosomal recessive disorder caused by mutations in the vitamin D receptor (VDR) gene. We report the case of an infant presenting with alopecia, growth failure, and gross motor developmental delay. Serum biochemistry and skeletal survey were consistent with rickets. After a poor response to standard treatment, genetic testing confirmed a c.147-2A>T novel mutation in the VDR gene consistent with HVDRR. It is important for dermatologists and pediatricians to recognize alopecia as a presenting sign of HVDRR because appropriate treatment leads to better growth and development of the child.