Molecular Profiling of Syringocystadenocarcinoma Papilliferum Reveals RAS-Activating Mutations.

CONTEXT.­: Syringocystadenocarcinoma papilliferum (SCACP) is a rare adnexal carcinoma and the malignant counterpart of syringocystadenoma papilliferum (SCAP), which is commonly located on the head and neck and may arise in association with a nevus sebaceus. RAS mutations have been identified in both SCAP and nevus sebaceus. OBJECTIVE.­: To evaluate the clinicopathologic and molecular features of SCACPs, which have not been previously explored. DESIGN.­: We obtained 11 SCACPs from 6 institutions and reviewed the clinicopathologic features. We also performed molecular profiling using next-generation sequencing. RESULTS.­: The cohort comprised 6 women and 5 men with ages ranging from 29 to 96 years (mean, 73.6 years). The neoplasms occurred on the head and neck (n = 8; 73%) and extremities (n = 3; 27%). Three tumors possibly arose in a nevus sebaceus. A total of 4 cases showed at least carcinoma in situ (adenocarcinoma, n = 3; squamous cell carcinoma [SCC], n = 1), and 7 cases were invasive (SCC, n = 5; mixed adenocarcinoma + SCC, n = 2). A total of 8 of 11 cases (73%) had hot spot mutations consisting of HRAS (n = 4), KRAS (n = 1), BRAF (n = 1), TP53 (n = 4), ATM (n = 2), FLT3 (n = 1), CDKN2A (n = 1), and PTEN (n = 1). All 4 cases with HRAS mutations occurred on the head and neck, whereas the KRAS mutation occurred on the extremity. CONCLUSIONS.­: RAS-activating mutations were detected in 50% of the cases, of which most (80%) involved HRAS and occurred on the head and neck, which shows overlapping features with SCAP, supporting that a subset may arise as a result of malignant transformation and likely an early oncogenic event.

Malignant Melanoacanthoma.

ABSTRACT: Melanoacanthomas are benign variations of seborrheic keratosis that have been known to mimic other common benign and malignant skin lesions. Therefore, the diagnosis typically requires biopsy and careful histologic examination. Here, we present the case of a 25-year-old woman initially diagnosed clinically with an epidermal inclusion cyst, but, on biopsy and further evaluation, was found to have histological features of an atypical or malignant melanoacanthoma. Contrary to typical cases of melanoacanthoma, histologic evaluation revealed atypical findings consistent with malignancy, such as tumor necrosis, marked cytologic atypia and pleomorphism, and numerous mitoses, including atypical forms, features consistent with malignancy (ie, similar to a squamous cell carcinoma in these areas). This report highlights the importance of histological evaluation in diagnosis and treatment of skin lesions because atypical presentations often occur and can delay correct diagnosis and appropriate treatment.

CD30 in Cutaneous Pathology.

ABSTRACT: The discovery of CD30 as a diagnostic marker was essential in the identification of not only some lymphomas but also many other solid tumors and benign reactive conditions. Many CD30+ cutaneous disorders and tumors have been categorized since the identification of the marker. With the design of targeted therapies against CD30+ tumoral cells, the interest in CD30 determination was not only diagnostic but also mainly therapeutic. In this article, we explore the historical aspects of the discovery of CD30 and examine the main CD30-related cutaneous pathology, susceptible of anti-CD30 modern treatments.

Disseminated and penile mpox with histopathologic correlation: Two separate case reports.

The 2022-2023 mpox outbreak is a global worldwide concern, especially since the virus was previously mainly localized regionally in Central and West Africa. The infection is typically self-limiting and transmitted by close contact/exposure with infected material. Recent cases have been known to present atypically without prodromal symptoms and initially with skin lesions. The histopathology of mpox lesions is rarely reported. Here, we present two middle-aged males presenting initially with painless skin lesions confirmed for mpox by nucleic acid amplification assay. Skin biopsies of the lesion were available for clinicopathologic correlation. Histopathology demonstrated ulceration with viral cytopathologic changes.

A rare case of cutaneous pseudoglandular schwannoma.

Schwannomas are benign tumors that arise from the peripheral nerve sheath. Many variants of schwannomas exist, including plexiform, epithelioid, cellular, glandular, and ancient. The pseudoglandular subtype is extremely rare, as fewer than five cases of cutaneous pseudoglandular schwannomas have been reported based on our literature review. Herein, we report a case of a 64-year-old female who presented with a skin-colored nodule on her right arm for several years. Histopathology showed a superficial and deep dermal nodulocystic neoplasm composed of epithelioid and spindle cells surrounded by a fibrous stroma. The epithelioid cells surrounded multiple spaces suggestive of glandular differentiation, although many of these spaces also contained serum and red blood cells, raising consideration for vascular differentiation. Multiple epithelial markers, including pancytokeratin and epithelial membrane antigen, were all negative, providing no support for an epithelial tumor with true ductal/glandular differentiation. In addition, CD31, CD34, smooth muscle actin, and desmin stains were negative in these spaces, making a vascular neoplasm or smooth muscle tumor unlikely. However, SOX10 and S-100 stains were positive, including in cells lining the pseudoglandular spaces, supporting the diagnosis of pseudoglandular schwannoma. Complete excision was recommended. This case highlights an extremely rare presentation of the pseudoglandular variant of schwannoma.

The Dermatopathology Books Before Unna.

ABSTRACT: Unna's book on dermatopathology was the one that achieved the greatest recognition in medicine and influenced the largest number of dermatopathologists in Europe at that time. However, several previous texts also gathered the requirements to be considered dermatopathological books. In this manuscript, we briefly examine some of the most relevant features of the dermatopathology books written by Simon, Leloir and Vidal, Auspitz, Bärensprung, and Jackson.

Central Centrifugal Cicatricial Alopecia Associated With PDL1 Loss and Increased Expression of Caspase 3: A Case Series.

ABSTRACT: Central centrifugal cicatricial alopecia (CCCA) is a scarring alopecia that disproportionately affects patients with skin of color. Genetic studies have revealed that approximately 30% of CCCAs are associated with peptidyl arginine deiminase 3 misfolding mutations. Patients with CCCA usually have a poor prognosis with progressive and permanent hair loss. To further characterize CCCA, we evaluated the inflammatory milieu, PDL1, and caspase 3 expression. The data support the idea of CCCA being a CD4-predominant T-cell process. The loss of PDL1 and increase in caspase 3 expression raises the possibility of involvement of the PD1/PDL1 pathway in CCCA.

Top 10 Differential Diagnoses for Desmoplastic Melanoma.

BACKGROUND: Desmoplastic melanoma is a rare subtype of melanoma mainly appearing on sun-exposed skin. Clinically, it is many times non-pigmented and therefore the diagnosis is often not suspected. METHODS: Review article. RESULTS: In this paper we review the main histopathological, immunohistochemical, and molecular features of desmoplastic melanoma, as well as the top 10 morphologic differential diagnoses which should be considered in most cases. The histopathological pattern can be many times deceptive, mimicking a scar, a fibrous reaction, a fibrohistiocytic tumor such as a dermatofibroma, a vascular tumor such as angiosarcoma, a smooth muscle tumor such as leiomyosarcoma, or a neural tumor. Although an overlying atypical junctional melanocytic proliferation may be seen in most cases, it is absent in a significant percentage (up to 30%) of cases, making the diagnosis even more difficult in those instances. The range of diagnostic pitfalls is wide, which may present disastrous prognostic consequences. CONCLUSION: Desmoplastic melanoma is often a difficult diagnosis to make, as it frequently shows nonspecific clinical findings and overlapping histologic features with many other tumors. However, the potential clinical and prognostic consequences of misdiagnosis as another entity are great. Therefore, this diagnosis must always be kept in mind when encountering spindle cell tumors affecting the head and neck area.

Pagetoid Spread in Basal Cell Carcinoma: Potential for Misdiagnosis.

ABSTRACT: Basal cell carcinomas are one of the most common cutaneous carcinomas and show classical histologic features of basaloid nests with peripheral palisading. Pagetoid and intraepidermal spread has not been described in basal cell carcinoma to the best of our knowledge. We report 5 cases of basal cell carcinoma with classic histologic patterns and overlying basaloid nests and single intraepidermal tumor cells. A panel of immunostains were performed that included CK7, MOC31, CEA-m, EMA, androgen receptor, and Bcl2. Most of our cases were positive for both MOC31 and CK7, and all cases were negative for CEA-m and EMA excluding extramammary Paget disease, one of the most common differential diagnoses. These cases expand the spectrum of findings that can be seen in basal cell carcinoma and can help prevent misdiagnoses of basal cell carcinomas as more aggressive tumors.

Sebaceous Carcinoma of the Penis: A Rare, Dangerous Clinical Entity and the Importance of Immunohistochemistry in Diagnosis.

We report a very rare case of pathologically confirmed sebaceous carcinoma of the glans penis with multiple areas of lymphovascular and perineural invasion and multiple lymph node metastases. The importance of immunohistochemical staining in diagnosis is also reviewed.

Ungual Keratoacanthoma With Features of Regression.

ABSTRACT: Ungual keratoacanthoma (UKA) is an infrequent tumor. Different from keratoacanthoma in other parts of the skin, UKA rarely regresses, and grows aggressively with common destruction of the subjacent phalanx. Reported cases of UKA with features of regression are exceptional, and even dermatopathologists with reputed experience in nail pathology admit to having seen very few cases. We herein report a case of a 77-year-old man who presented a painful subungual lesion on the second finger of the right hand. An x-ray showed evidence of erosion of the subjacent distal phalanx. The patient was highly concerned about the lesion and rejected conservative treatment preferring amputation of the distal phalanx. The histopathologic examination revealed a UKA with features of regression.

Genetic Studies on a Case of Eruptive Disseminated Spitz Nevus and Review of Other 33 Cases.

ABSTRACT: Eruptive disseminated Spitz nevus is an uncommon presentation of Spitz nevi. Only a few tens of cases have been published and only 6 of them have genetic studies. We present an additional case of a 29-year-old woman with dozens of Spitz nevi which had appeared since she was aged 10 years. The nevi were located on arms, inner thighs, legs, and buttocks. Nine of them were biopsied. Four presented severe atypia. Immunohistochemistry was performed on 5 of the biopsied specimens and was negative for PRAME, ROS-1, PDL-1, pan-TRK, and ALK. Molecular studies on the largest lesion demonstrated no NTRK1, NTRK2, or NTRK3 fusions. FISH study for PTEN showed no alteration in that same lesion. Next-generation sequencing was also negative for any detectable mutations in numerous genes analyzed. In conclusion, it seems reasonable to be cautious when evaluating atypia, even if severe, in cases of eruptive disseminated Spitz nevus.

Pigmented Multinucleate Cell Angiohistiocytoma: First Case.

ABSTRACT: Multinucleate cell angiohistiocytoma (MCAH) is a benign vascular and fibrohistiocytic (probably reactive) proliferation with peculiar multinucleate cells which most authors interpret as degenerated macrophages. Several clinical variants of MCAH have been described, some of them with brownish-appearing lesions clinically. However, no histologically identified pigment has been described in the cytoplasm of the multinucleate cells so far. We present a pigmented MCAH with cytoplasmic brownish pigment, which was positive with a Masson-Fontana stain and negative with an iron stain, consistent with melanin, in a 33-year-old woman with multiple papules and plaques on the right elbow, right jawline, and left flank.

Folliculosebaceous Cystic Hamartoma With Prominent Adipose Tissue Resembling Spindle Cell Lipoma.

ABSTRACT: Folliculosebaceous cystic hamartomas (FSCH) are a rare form of cutaneous hamartoma composed of follicular, sebaceous, and mesenchymal elements. These lesions are most often seen in the central face and scalp and rarely exceed 2 cm in size. Here, we report a case of a folliculosebaceous cystic hamartoma with a prominent adipose tissue component resembling a spindle cell lipoma. The patient is a 36-year-old man with a slowly enlarging, flesh-colored, lobulated lesion on his right ala that had been previously biopsied. The clinical differential included a hypertrophic scar or recurrent hamartoma. A full-thickness excisional biopsy was performed, which revealed prominent, large, irregularly shaped, folliculosebaceous structures, including multiple dilated follicles associated with prominent hyperplastic-appearing sebaceous glands, findings consistent with FSCH. The mesenchymal component contained a proliferation of spindle-shaped cells associated with mucin and thickened, ropey-appearing bundles of collagen, features mimicking a spindle cell lipoma. This combination of a folliculosebaceous cystic hamartoma with prominent adipose tissue resembling spindle cell lipoma is unusual and has only been previously reported once in the literature, and therefore, our case contributes to the expanding knowledge of this rare variant of FSCH.