Journal
Vulvar Pigmented Epithelioid Melanocytoma With a Novel HTT-PKN1 Fusion: A Case Report
Abstract: Pigmented epithelioid melanocytoma is a highly pigmented, predominantly dermal melanocytic neoplasm composed by epithelioid and spindled melanocytes. It is characterized by a limited number of specific genomic alterations principally involving protein kinase A regulatory subunit alpha (PRKAR1A) and fusion of protein kinase C alpha isoform (PRKCA). However, in some of these neoplasms, no genetic aberrations have been detected. We performed genomic analysis of a nodular heavily pigmented intradermal proliferation composed of monomorphic epithelioid melanocytes with slight cytologic atypia consisting with pigmented epithelioid melanocytoma occurring on the vulva of a 24-year-old woman. A novel fusion transcript HTT-PKN1 and an ATM (Val410Ala) missense mutation were found. No other mutations including TERT-promoter hotspot mutation analysis were detected. The data expand the spectrum of molecular alterations in pigmented epithelioid melanocytoma.
Diagnostic Utility of Preferentially Expressed Antigen in Melanoma (PRAME) and p16 Immunohistochemistry in Distinguishing Genital Melanomas From Benign Melanocytic Proliferations
Abstract: Preferentially expressed antigen in melanoma (PRAME) expression is valuable for distinguishing malignant from benign melanocytic proliferations, and p16 has also been shown to aid in this distinction. However, data on the utility of these two immunohistochemistry stains in genital melanocytic lesions are limited. We retrospectively analyzed 56 genital melanocytic lesions, including 41 benign lesions and 15 melanomas (6 in situ and 9 invasive) with PRAME and p16 immunohistochemistry. All melanomas exhibited extensive PRAME positivity: 93.3% (14 of 15) had a 4+ score (>75% positive cells) and 1 had a 3+ score (51%–75% positive cells). In contrast, 87.8% (36 of 41) of benign lesions were PRAME negative, and none scored higher than 2+ (26%–50% positive cells). Using a 4+ cutoff, PRAME demonstrated a sensitivity of 93.3% and specificity of 100%. Lowering the cutoff to 3+ increased sensitivity to 100%. Complete or partial loss of p16 was observed in 60.0% (9 of 15) of melanomas but not in any benign lesions (0 of 41), resulting in a sensitivity of 60.0% and specificity of 100%. Our findings indicate that PRAME immunohistochemistry is highly sensitive and specific for genital melanoma. Loss of p16 expression, although not sensitive, is highly specific for genital melanomas and is, therefore, useful in challenging genital melanocytic lesions.
Melanotic Schwannoma of the Vulva: A Case Report and Review of the Literature
Abstract: Melanotic schwannoma is a pigmented tumor of peripheral nerve differentiation. Primary cutaneous presentations are extremely rare, as the bulk of melanotic schwannomas tend to develop in paraspinal and axial sites. Tumors arise sporadically and in the setting of the Carney complex. Alterations in the gene encoding protein kinase A regulatory subunit-α (PRKAR1A) underlie most patients with the Carney complex and mediate melanotic schwannoma tumorigenesis. Melanotic schwannomas from noncutaneous sites can locally recur and metastasize widely, leading to a recent proposal to change the nomenclature to “malignant melanotic schwannian tumor.” However, the clinicopathologic features of primary cutaneous melanotic schwannomas are relatively unexplored. We present a case of a nodule arising on the vulva of a 34-year-old woman. Microscopically, a dermal-based, heavily pigmented proliferation of plump spindled and epithelioid cells arrayed in nodules and fascicles was seen. Lesional cells stained positively for S100, Melan-A, and BAP1 but were negative for Prkar1α. Next-generation sequencing of a panel of 480 cancer-associated genes revealed that the tumor harbored a PRKAR1A p.S299fs truncating mutation and copy neutral loss of heterozygosity of chromosome 17q, the locus at which PRKAR1A resides. Importantly, no other genetic abnormalities or chromosomal copy number changes were identified. On the basis of combined histopathologic, immunohistochemical, and genetic features, a diagnosis of melanotic schwannoma was rendered. Overall, we present the first clinicopathologic description of a vulvar melanotic schwannoma, review the literature concerning cutaneous presentations of melanotic schwannoma, and propose that melanotic schwannian tumors native to skin may behave more indolently than their noncutaneous counterparts.
Ectopic Lactating Adenoma of Breast Presenting as a Vulvar Tumor
Abstract: Ectopic breast tissue is a rare occurrence that has been well-documented along the length of the milk lines. For the most part, ectopic breast is easily recognizable on routine histology; however, difficulties may arise when dealing with tumors arising from such tissues, such as adenomas or carcinomas. We report the case of a 29-year-old pregnant woman who presented with a 1.6-cm cystic lesion in her vulva. Surgical excision was performed which showed a well-circumscribed tumor composed of compact tubular structures lined by columnar cells with round nuclei and small nucleoli devoid of mitotic activity. The tubular structures were remarkable for the presence of numerous clear vacuoles in the cytoplasm resulting in a histologic picture that is indistinguishable from so-called “lactating” adenomas of the breast. Immunohistochemical stains demonstrated nuclear positivity of the cells lining the ductules for estrogen and progesterone receptors, GATA3, and cytoplasmic staining for mammaglobin, supporting the breast origin of the tissue. Recognition of this lesion is of importance to avoid misdiagnosis of malignancy.
An Unusual Vulvar Mass in a Middle-Aged Woman: Challenge
An Unusual Vulvar Mass in a Middle-Aged Woman: Answer
An Unusual Vulvar Mass in an Adolescent: Challenge
Vulvar Nocardiosis in the Setting of dVIN: A High-Risk Infection
Abstract: Nocardia is a Gram positive, aerobic, partially acid-fast filamentous bacteria of the order Actinomycetales. It is a saprophytic organism found in environmental contaminants such as soil and decomposing organic matter. Primary cutaneous nocardiosis is uncommon and may occur through contamination of a wound or through inhalation of the organism with dissemination to multiple organ systems, including the skin. Vulvar nocardiosis is an exceedingly rare manifestation of Nocardia. Described is a patient with a history of lichen sclerosus, differentiated vulvar intraepithelial neoplasia (dVIN), and recurrent vulvar squamous cell carcinoma requiring multiple resections and biopsies who presented with recurrent firm, white, nodular lesions on the right labia and right inferior clitoris. Histopathology of the right inferior clitoral lesion demonstrated dVIN. The right labia majora lesion also revealed dVIN and a dermal epithelioid granuloma with central vacuoles filled with filamentous to small, fragmented forms suggestive of bacteria. Ziehl-Neelsen AFB stain was negative. Gram stain, Gomori methenamine silver (GMS), and FITE stains were positive. The staining pattern of the filamentous and beaded forms supports a diagnosis of Nocardia. Vulvar nocardiosis in the setting of dVIN and history of multiple vulvar surgeries has not been described in the literature to date. This case demonstrates the importance of maintaining atypical infections on the differential for nonhealing vulvar wounds. Timely treatment is crucial to improve outcomes, particularly in the setting of multiple surgical procedures in patients at high risk for infectious complications.
An Unusual Vulvar Mass in an Adolescent: Answer
A Mimicker of Differentiated Vulvar Intraepithelial Neoplasia: Reactive Atypia From Noncompliance With Lichen Sclerosus Therapy
Abstract: Differentiated vulvar intraepithelial neoplasia (d-VIN) is an HPV-independent precursor to vulvar squamous cell carcinoma. The histology of d-VIN lesions is difficult to differentiate from that of non–neoplastic epithelial disorders, especially lichen sclerosus (LS). The authors present a case of LS, where relying on histopathology alone could have led to misdiagnosis. The patient was a 17-year-old female patient with clinical features of vulvar dermatitis and LS for 2 years. She was counseled to apply clobetasol 0.05% to the affected area daily but reported no improvement after 6 months. A biopsy of the right labia majora revealed histologic findings typical of d-VIN and near-contiguous p53 expression. These features are characteristic of d-VIN. However, d-VIN is exceedingly rare in young patients. The case was reviewed by 6 dermatopathologists and gynecologic pathologists, who observed that the degree of inflammation would be unusual postclobetasol therapy and could be due to noncompliance. A review of the patient's chart revealed that she “does not always remember to apply” clobetasol. The patient's clinician confirmed that there were compliance issues, and the follow-up biopsy was negative for d-VIN. The case was signed out as LS, with a note describing the above, and to rebiopsy if concern persisted. The authors conjecture that inflammatory infiltrates in the biopsied area caused reactive atypia due to lack of adherence to treatment. Although the patient's age helped rule out d-VIN, similar cases in elderly patients may be occurring. Pathologists must be aware that reactive forms of untreated LS can mimic d-VIN, to avoid misdiagnosis.
A Rare Presentation of an Isolated Vulvar Lesion in an Elderly Female: Challenge
Podophyllotoxin Cytological Effects on the Epidermis in Condyloma Acuminatum
Abstract: Podophyllotoxin (PPT) is used to treat condylomata acuminata and works by destabilizing microtubules within epithelial cells, leading to mitotic arrest in metaphase. PPT-induced changes to the epidermis can cause histological findings mimicking dysplasia. Here, we present a case of vulvar condyloma acuminatum treated with PPT, showing ballooning degeneration, necrotic keratinocytes, and mitotic figures. PPT-treated skin may resemble dysplasia or squamous cell carcinoma in situ due to dyskeratosis and frequent mitoses; however, the synchronicity of mitotic figures in early phases of mitosis, as well as the absence of cellular pleomorphism and atypical mitotic figures, allows for distinction from malignancy. This case demonstrates the importance of understanding the histological changes caused by PPT to prevent misdiagnosis and potential overtreatment.
Vulvar Skin Metastasis From Cervical Adenocarcinoma
Abstract: Cervical cancer stands as one of the most common gynecologic malignancies in developing countries; however, cutaneous metastasis from cervical cancer is a rare occurrence. In this study, we present a case involving a 44-year-old woman diagnosed with International Federation of Gynecology and Obstetrics stage IIA gastric-type endocervical adenocarcinoma. Two years later, after undergoing radical hysterectomy and chemoradiation therapy, she exhibited cutaneous metastasis in the vulvar region.
Molecular Alterations in Vaginal Melanomas: Report of 4 Cases and Literature Review
Abstract: Melanomas of the female gynecological tract comprise approximately 18% of mucosal melanomas, a rare subtype of melanoma. Within the female genital tract, 70% of primary melanomas of the gynecological tract are from the vulva with the remainder occurring in the vagina and rarely, in the cervix. We investigate molecular alterations by next-generation sequencing-based molecular tests targeting 99 cancer genes and translocation/fusion assays in 4 and 3 vaginal melanomas, respectively. The ages of the 4 patients range from 65 to 90 years. Postmenopausal bleeding was the most common presenting symptom. Tumor size ranged from 0.5 to 6.6 cm. KIT L576P mutation was documented in case 1, whereas TP53 mutation was seen in cases 2 and 3 (L130F and Y163C). Case 2 also harbored NF2 E204Q and ATRX D1719H mutations. A number of gene copy alterations were noted in case 4, which included GNA11 loss, MYC gain, RET loss, SMO loss, SUFU loss, and TSC2 loss. No gene fusion was detected in any of the 3 tested cases. In conclusion, in addition to KIT, TP53, and ATRX mutations, which have been previously reported, our cases harbor NF2 mutation and multiple gene copy alterations that have not previously been documented in vaginal melanomas. These findings highlight the potential role of targeted therapy in this rare melanoma subtype.
Pembrolizumab-Induced Stevens–Johnson Syndrome/Toxic Epidermal Necrolysis in a Patient With Metastatic Cervical Squamous Cell Carcinoma: A Case Report
Abstract: We present a rare case of a pembrolizumab-induced Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). A 55-year-old woman with a history of metastatic cervical squamous cell carcinoma presented with a widespread mucocutaneous rash. Seventeen days after receiving her first cycle of pembrolizumab, she presented with fever, difficulty breathing, watery eyes, and painful oral ulcers. Physical examination revealed widespread erythematous papules and papulovesicles involving the trunk, upper extremity, and lower extremity and hemorrhagic plaques on the lower lip and buccal mucosa. Biopsy confirmed a diagnosis of SJS/TEN. This case highlights the importance of awareness of SJS/TEN as a possible adverse reaction for patients receiving pembrolizumab, a medication increasingly being used to treat metastatic or unresectable malignancies.
Recurrent Papillary Apocrine Carcinoma of the Vulva
Abstract: Apocrine carcinoma of the vulva is a rare form of vulvar cancer, with the papillary subtype being even more uncommon. There are less than 20 reported cases of vulvar apocrine carcinoma, and only 2 reported cases specifically of the tubulo-papillary subtype. Here we discuss the case of a woman in her mid-50s who presented with recurrent vulvar papillary apocrine carcinoma and was treated with wide local excision. Prognosis and treatment guidelines are not standardized because of the rarity of this condition. Given that the incidence of vulvar cancer has been rising in younger women and can initially present with subtle findings, these rarer subtypes should be considered in the differential for any unusual vulvar lesion.
Digital Papillary Adenocarcinoma of the Vulva
Abstract: Digital papillary adenocarcinoma (DPAC) is an uncommon cutaneous adnexal tumor that predominantly involves the skin of the fingers and toes and is associated with human papillomavirus 42 infection. The histologic features can be deceptively bland, but awareness of the entity in typical locations facilitates diagnosis. We describe a case of extradigital DPAC arising in vulvar skin, with the diagnosis confirmed using in situ hybridization for HPV42. Extradigital DPAC is very rare and presents a significant diagnostic challenge, particularly in this anatomical location where a range of other more common tumors with solid, tubular, and papillary architectures are much more frequently recognized.
Pigmented Syringomatous Carcinoma/Sweat Gland Carcinoma of the Vulva With Melanocytic Colonization: An Uncommon Presentation of a Rare Sweat Gland Neoplasm
Abstract: Primary vulvar carcinomas are rare and constitute a diverse group of neoplasms. These primary tumors are typically classified based on their presumed tissue of origin or histological characteristics. Among these, carcinomas of sweat gland origin are particularly significant. They closely resemble similar malignancies in nonvulvar skin, including various cutaneous adnexal-type cancers such as apocrine and eccrine adenocarcinomas. Syringomatous carcinoma of the vulva is a rare malignant sweat gland neoplasm known for its infiltrative growth and tendency for local recurrence. Typically, these malignancies manifest as nonulcerated nodules or plaques, primarily in the head and neck region. The occurrence of syringomatous carcinoma in the vulvar region is exceptionally rare. Herein, we present a unique case of a 35-year-old woman with a dark mole measuring 1.5 × 1.0 cm on the vulva. Complete excision was performed to exhibit an infiltrative haphazard proliferation of elongated ductules and tubules, displaying significant cytologic atypia characterized by irregular nuclear contours and variably prominent nucleoli. Extensive melanocytic pigment deposition and stromal fibrosis were also observed. Immunohistochemical staining demonstrated positive expression of epithelial markers, including keratins (AE1/AE3) and epithelial membrane antigen, supporting the diagnosis of syringomatous carcinoma. CK7 and carcinoembryonic antigen were negative, whereas SOX10 and pan melanin highlighted admixed, cytologically bland melanocytes within the epidermis and neoplastic nests. This case represents a highly unusual presentation of syringomatous carcinoma associated with melanocyte colonization. Due to limited data on the optimal management strategies, a multidisciplinary approach involving gynecologic oncologists, dermatopathologists, and radiation oncologists is essential for treatment decisions. Long-term follow-up is crucial, considering the potential for local recurrence and metastatic spread, emphasizing the importance of comprehensive clinical management for favorable patient outcomes of this rare malignancy.
Pedunculated Neoplasm of the Vulva
Abstract: Extramammary Paget disease (EMPD) is a rare cutaneous malignancy, typically presenting as eczema-like lesions in areas rich in apocrine glands such as the perineum. Here, we report a case of EMPD presenting as a prominent pedunculated neoplasm in a 65-year-old woman. Despite initial misdiagnosis and treatment, biopsy confirmed EMPD infiltration. Following surgical excision, the patient developed brain metastases, indicating a poor prognosis. EMPD's pathogenesis remains unclear, but distinguishing primary from secondary forms is crucial for prognosis and treatment. Our case underscores the importance of recognizing atypical EMPD presentations for timely intervention and improved outcomes.
Solitary Vulvar Syringoma With Deep Extension; Potential for Misdiagnosis as the Microcystic Adnexal Carcinoma (MAC)
Abstract: A 43-year-old woman presented with a palpable, pruritic, minimally painful right vulvar lesion. Physical examination revealed approximately 2.0-cm tender nodule at 70’ clock in the right labia majora. Histological sections of the excision specimen showed an unremarkable epidermis with large, well-circumscribed dermal proliferation with extension to the reticular dermis. Within this proliferation are small solid and ductal structures relatively evenly distributed in the sclerotic stroma. The epithelial elements consisted of monomorphous cuboidal cells and assumed round, oval, curvilinear, or have other peculiar geometric shapes, including “comma-like” or “tadpole”-like configurations. The tumor cells were positive for CEA, EMA, and estrogen receptor and negative for progesterone receptor. The clinical presentation and the deep extension of the tumor were similar to the microcystic adnexal carcinoma. Although a syringoma generally presents with multiple lesions and usually involves the superficial dermis, a syringoma with deep extension was favored based on the lack of follicular differentiation, atypia, mitoses, and perineural invasion. Microcystic adnexal carcinoma and syringoma have a morphologic overlap and are misdiagnosed in 30% of the cases. Thus, it is exceptionally important for pathologists to be aware of and be able to distinguish these entities. To the best of our knowledge, this is the first case of a solitary, painful vulvar syringoma with deep extension.
A Rare Collision of Vulvar Melanoma and Extramammary Paget Disease: Case Report and Review of the Literature
“Dark Paget” Cells in Extramammary Paget Disease: A Staining Artifact and Diagnostic Pitfall
A Woman With a Rapidly Expanding Subungual Mass: Subungual Endometrial Carcinoma Metastasis
Ovid Technologies (Wolters Kluwer Health)
0193-1091
