Journal of Cutaneous Pathology

A pilot study of p53 immunohistochemistry in atypical squamous lesions, using a vulvar scoring system

AbstractBackgroundHistopathologic overlap between cutaneous squamous cell carcinoma (cSCC) and its indolent mimics likely leads to the overdiagnosis of cSCC.ObjectiveTo perform a pilot study of the p53 immunohistochemical scoring system developed on vulvar squamous lesions in cSCC.MethodsThe consistency and reliability of p53 immunostaining using a scoring system developed on vulvar cases, as compared with TP53 genomic sequencing, was studied in an initial cohort of 28 cutaneous cases. p53 labeling was further assessed in an additional 63 cases of atypical squamous lesions, including 20 atypical squamous lesions classified by the authors as benign, 22 cases diagnosed as cSCC without high‐risk features, and 21 cases of high‐risk cSCC (cSCC‐HR).ResultsThe concordance of p53 labeling and TP53 sequencing was 82.1%. Four positive patterns of p53 mutation were identified: basal, parabasal/diffuse, null, and cytoplasmic. p53 positivity in atypical, benign squamous lesions (10%) was significantly lower than that of low‐risk cSCC (63.6%, p = 0.0004) or cSCC‐HR (90.5%, p < 0.0001). p53 positivity in low‐risk cSCC versus cSCC‐HR was not statistically significant (p = 0.07).Conclusionp53 Labeling may be a helpful biomarker to support the diagnosis of cSCC and distinguish cSCC from atypical but benign mimics.

Malignant glomus tumor arising in association with a fumarate hydratase‐deficient leiomyoma: An unusual collision tumor

AbstractCollision tumors, defined as “two independent neoplasms that occur in close proximity to one another but maintain distinct boundaries,” are quite rare. We report an exceptional collision tumor composed of a genetically confirmed malignant glomus tumor and a fumarate hydratase (FH)‐deficient leiomyoma, presenting as a subcutaneous thigh mass in a 38‐year‐old male who was known to have hereditary leiomyomatosis and renal cell carcinoma syndrome. Microscopic examination identified a biphasic subcutaneous mass comprising sheets and nodules of glomus cells, with nuclear atypia and mitotic activity, and fascicles of mitotically inactive smooth muscle with variably pleomorphic nuclei and intracytoplasmic eosinophilic inclusions, features of FH‐deficient leiomyoma. Immunohistochemistry demonstrated loss of FH and robust 2‐succinocysteine expression in the smooth muscle, with a normal (FH‐retained) expression pattern in the glomus tumor. Next‐generation sequencing, performed on the glomus tumor component, identified CARMN::NOTCH2 fusion, characteristic of malignant glomus tumors. Awareness of the distinctive morphologic, immunohistochemical, and molecular genetic features of glomus tumors and FH‐deficient leiomyomas is important for correct clinical management of patients with exceptional collision tumors of this type.

Cutaneous Clear Cell Sarcoma in the Genital Region: A Report of Two Cases at an Unusual Location

ABSTRACT Clear cell sarcoma (CCS) is a rare sarcoma that typically arises in the deep soft tissue of the extremities. We describe two patients with molecularly confirmed CCS in genital skin. Patient 1 was a 22‐year‐old woman with a vulvar mass, and Patient 2 was a 25‐year‐old man with a scrotal plaque. Histopathological examination in each case revealed a cellular tumor distributed in nests and sheets, composed of epithelioid and spindled cells. The tumor cells exhibited clear and eosinophilic cytoplasm, vesicular nuclei, and prominent nucleoli. Immunohistochemical analysis demonstrated that both tumors expressed Sox10 and HMB45. FISH testing revealed EWSR1 rearrangements in both cases, and further NGS analysis in Case 1 confirmed the presence of an EWSR1 ‐ ATF1 fusion. To date, only 3 cases of CCS have been reported involving the genital region, all originating in deep soft tissues. Our report expands the known anatomical sites of cutaneous clear cell sarcoma involvement.

PRAME Immunohistochemistry for Differentiating Pigmented Lesions of the Vulva and Perineum

ABSTRACTSpecial site pigmented lesions often present a diagnostic challenge for clinicians and for pathologists. Lesions of the genital region present even further challenges due to the sensitivity of the anatomic location and preference to defer physical exam and biopsy. Even after biopsy, the diagnostic challenge persists owing to the frequent presence of atypical features in these sites and the technical difficulties associated with performing complete excisions. Immunohistochemistry plays a crucial role in the classification and categorization of these lesions. PRAME (PReferentially expressed Antigen in MElanoma) is a nuclear receptor and transcriptional regulator that regulates cell differentiation, growth, and apoptosis. Immunohistochemistry for PRAME has proven valuable in assisting pathologists to classify various cutaneous melanocytic proliferations all over the human body. Our study sought to investigate the use of PRAME in determining the biologic nature of pigmented lesions of the genital region. A search of medical records identified 53 cases of genital pigmented lesions for review. Each case received MART1 and PRAME IHC for evaluation and classification by two board certified dermatopathologists. The results found that PRAME was negative (zero nuclear staining) in a total of 32 benign lesions (i.e., melanosis including macules and lentigos as well as nevi). One dysplastic nevus showed focal weak PRAME expression in less than 10% of lesional melanocytes. PRAME was overwhelmingly positive (4+ staining, > 75% of nuclei) in 90% of the malignant lesions (i.e., invasive melanoma and melanoma in situ). Overall, we conclude that PRAME remains a valuable tool in the diagnostic workup of diagnosing pigmented lesions of the genital region.

Adenocarcinoma of anogenital mammary gland type arising from encapsulated papillary carcinoma: A rare vulvar tumor mimicking breast carcinoma

AbstractAnogenital mammary‐like glands are normal structures of the anogenital region. Tumors originating from these glands often exhibit a striking resemblance to their mammary gland counterparts. Herein, we present a rare case of adenocarcinoma of mammary gland type in the vulva of a 69‐year‐old female. Histopathologic examination revealed a complex lesion, which included a large encapsulated papillary carcinoma (EPC) with associated invasive carcinoma of mammary gland type and ductal carcinoma in situ (DCIS). The invasive component consisted mostly of invasive ductal carcinoma of no special type, with a notable focus of invasive mucinous carcinoma. p40 immunostain demonstrated a lack of myoepithelial cells in both the EPC and invasive carcinoma, but such cells expressed p40 around the ducts involved by DCIS. The main component of this lesion, EPC, was characterized by a papillary proliferation within a cystic space surrounded by a fibrous capsule without a myoepithelial layer. The histopathologic features of anogenital EPC closely resemble cutaneous hidradenoma papilliferum. Indeed, there have been a few reports in the literature describing cases where in situ and invasive carcinoma arose from a preexisting hidradenoma papilliferum. As tumors of anogenital mammary‐like glands bear a closer resemblance to breast lesions than to skin tumors, we recommend that they be aligned with the classification of well‐established breast lesions rather than cutaneous adnexal tumors.

Vulvar dermatoses—Can a pattern‐based approach improve diagnostic yield?

AbstractBackgroundVulvar dermatoses (VD) pose a formidable challenge to clinicians and pathologists owing to various factors. The factors included are the histopathological heterogeneity of the vulva, moist and frictional environment, and the limited experience of gynecologists and general histopathologists in this field. To address this issue, the International Society for the Study of Vulvovaginal Disease (ISSVD) proposed a histopathological tissue reaction‐based classification system for VD. Therefore, we attempted to study the utility of the 2006 ISSVD classification in reporting VD. We further evaluated if a dermatopathologist review could improve the diagnostic yield.Materials and MethodsThe vulvar biopsy reports (N = 106) were retrieved from histopathology case files, out of which benign non‐infectious conditions (n = 55) were included in the study. The diagnosis retrieved from the case files was considered the initial diagnosis. Three dermatopathologists reviewed each biopsy, and a tissue reaction pattern/diagnosis was assigned as per ISSVD 2006, and this was considered a review diagnosis. The initial and review diagnoses were compared and analyzed. We further studied and analyzed the effect of the dermatopathologist's review on the diagnostic yield.ResultsThe sclerotic pattern (34.6%) was the commonest tissue reaction pattern, followed by spongiotic (18%) and acanthotic patterns (14.5%) independently or in combination. The non‐specific/descriptive report rate was significantly decreased following 2006 ISSVD and the dermatopathologist's review (83.6% vs.1.8%).ConclusionRendering tissue reaction patterns to vulvar biopsies will enable a comprehensive understanding of lesions and aid in clinically relevant reporting. In addition, dermatopathologists' review of difficult vulvar biopsies increases the diagnostic yield.

Non‐human‐papillomavirus‐related malignancies of the vulva: A clinicopathological study

AbstractBackgroundMalignant tumor of the vulva is the fourth gynecological malignancy in frequency. Close to 70% of all vulvar malignancies are related to high‐risk human papillomavirus (HPV) infection.MethodsA search for non‐HPV‐related malignant tumors of the vulva was performed in the last 20 years (2000‐2020) in the pathology database of a single tertiary institution. We aim to estimate the prevalence of non‐HPV‐related malignancies in our population, describe clinicopathological features of these tumors and investigate the expression of some potential therapeutic targets.ResultsA total of 71 patients were recovered; 26 patients (36%) had the diagnosis of extramammary Paget disease, 17 patients (24%) had basal cell carcinomas, 17 patients (24%) had primary melanomas, 10 patients (14%) had metastatic disease to the vulva and one patient (1%) had a primary dermatofibrosarcoma protuberans. Fifty‐four percent of patients with extramammary Paget disease had a secondary malignancy and 12.5% had invasive disease. Programmed death‐ligand 1 (PDL‐1) was positive in seven out of nine primary melanomas and Her2/neu was overexpressed in six out of seven extramammary Paget disease.ConclusionNon‐HPV‐related malignancies are important differential diagnoses in patient with vulvar lesions. Additional research is necessary to further understand these complex malignancies and potential new therapeutic targets.

Vulvar phyllodes tumor presenting as an epidermoid cyst

Fibroadenoma of the vulva with pseudoangiomatous stromal hyperplasia: A common neoplasm in uncommon site

AbstractMammary‐type tissue in the vulva was first described in 1872 but has been rarely reported in the literature. This tissue was previously considered as ectopic breast tissue that occurs as a result of incomplete regression of the milk line. Similar to native breast tissue, ectopic mammary tissue is hormone‐sensitive and can develop benign changes, such as fibroadenoma, as well as malignant changes. A more recent theory suggests that these benign and malignant mammary‐type entities arise from mammary‐like anogenital glands, which constitute normal vulvar components. We report a case of a 41‐year‐old woman who presented with a chronic asymptomatic cyst on the left vulva that eventually became uncomfortable, especially on standing. The cyst was located on the labium minus, measuring 1.0 × 0.5 cm, with no identified erythema or other skin abnormalities. Excision of the lesion and subsequent microscopic examination showed a circumscribed mass with a nodular overgrowth of epithelial and stromal components, resembling a mammary fibroadenoma with pseudoangiomatous stromal hyperplasia. We bring to attention this rare diagnosis and the importance of considering it in the presence of a vulvar lesion. The malignant and recurrence potential of mammary‐type tissue necessitates excision with clear margins and close monitoring of these patients.

Sporadic fumarate hydratase‐deficient cutaneous leiomyomatosis

Malignancy‐associated acquired vulvar lymphangioma circumscriptum: A clinicopathologic study of 71 cases

AbstractBackgroundAcquired lymphangioma circumscriptum of the vulva is rare and can occur subsequent to malignancies of the anogenital and pelvic region. We sought to investigate the clinicopathologic characteristics of malignancy‐associated acquired vulvar lymphangioma circumscriptum (AVLC).MethodsWe identified all cases of AVLC within our institution with history of prior malignancy between 2005 and 2021. A similar search was performed in the PubMed database to identify published cases to date. The clinical and histopathologic information was recorded.ResultsA total of 71 cases were identified. The most common preceding malignancy was cervical carcinoma (71.8%, 51/71). Radiation therapy was given to 91.4% (64/70) of the patients and lymph node dissection was made on 70.2% (40/57). Median interval between the diagnosis of malignancy and the AVLC was 10 years (range 0‐32 years). AVLC frequently presented as vesicular (31.6%, 18/57) or verrucous (28.1%, 16/57) lesions clinically. Common treatments for AVLC included excision (53.1%, 26/49) and laser therapy (16.3%, 8/49), with an overall recurrence rate of 42.9% (24/56) at a median follow‐up interval of 1.8 years (range 0.04‐32.3 years).ConclusionAVLC is a rare, late complication of anogenital and pelvic malignancies causing debilitating physical symptoms and psychological stress. Further studies are warranted to determine the most effective treatment modalities to mitigate recurrence.

Vulvar apocrine hidradenocarcinoma arising in a hidradenoma papilliferum—A case report

AbstractHidradenoma 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.