Plasma Cell Vulvitis: A Classification Into Two Clinical Phenotypes.

OBJECTIVE: The etiology of plasma cell vulvitis (PCV) is debated. The authors aimed to test the hypothesis that PCV could be divided into 2 clinical phenotypes. METHODS: Patients with a clinico-pathological diagnosis of PCV and with available vulvar photos seen in a vulvar clinic were retrospectively studied. The cases of PCV were divided into 2 groups: non-lichen-associated (primary PCV) and lichen-associated (secondary PCV). The 2 groups were compared in terms of age, menopausal status, location of the PCV, and 12 histologic parameters (Fisher exact test, p < .05). RESULTS: Thirty-five patients (20 primary and 15 secondary PCV) were included. The 2 groups did not differ in terms of age (mean, 65; range, 50-85) or menopausal status. Primary PCV was located exclusively on the vestibule for 19/20 patients, whereas secondary PCV was extravestibular for 14 of 15 patients, either exclusively (2) or both extravestibular and vestibular (12). One patient with secondary PCV had solely vestibular involvement. Five histological features were observed significantly more often in case of secondary PCV: epidermal atrophy, parakeratosis, dermal and epidermal neutrophils, and dermal eosinophils. CONCLUSIONS: Plasma cell vulvitis can be divided clinically into 2 phenotypes. Primary non-lichen-associated PCV is restricted to the vestibule and could be the vulvar counterpart of atrophic vaginitis. Secondary lichen-associated PCV is both extravestibular and vestibular, and its clinical and histological features should be looked for outside the PCV areas. This division of PCV into 2 clinical phenotypes could have therapeutic implications.

"Plasma cell gingivitis" encompasses multiple entities: a retrospective series of 37 cases.

BACKGROUND: Plasma cell gingivitis is defined as gingival inflammation comprised of plasma cell infiltrates. This diagnostic criterion is non-specific and underlying mechanisms remain unknown. OBJECTIVES: We performed a multidisciplinary clinico-pathological review of cases previously identified as "gingivitis with plasma cell infiltrates", with assessment of putative contributing factors and critical appraisal of the final diagnosis. MATERIALS & METHODS: Cases previously identified as "gingivitis with plasma cell infiltrates" between 2000 and 2020 were included from archives from the GEMUB group, a French multidisciplinary network of physicians with expertise on oral mucosa. RESULTS: Among the 37 included cases, multidisciplinary clinico-pathological review allowed differential diagnosis in seven cases (oral lichen planus n=4, plasma cell granuloma n=1, plasmacytoma n=1, and mucous membrane pemphigoid n=1). The remaining cases were classified as "reactive plasma cell gingivitis" (induced by drugs, trauma/irritation or periodontal disease) (n=18) or "idiopathic plasma cell gingivitis" when no contributing factors were identified (n=12). Clinico-pathological characteristics did not differ significantly between "reactive" and "idiopathic" cases, preventing us from identifying specific features of "idiopathic" plasma cell gingivitis. CONCLUSION: "Plasma cell gingivitis" is a polymorphous, non-specific entity with various aetiologies, of which the diagnosis requires multidisciplinary anatomo-clinical correlation for exclusion of secondary causes of plasma cell infiltration. Although our study was limited by its retrospective design, most cases of "plasma cell gingivitis" appeared to be associated with an underlying cause. We propose a diagnostic algorithm to properly investigate such cases.

Recurrent FOXK1::GRHL and GPS2::GRHL fusions in trichogerminoma.

We report 21 cases of trichogerminoma harbouring previously undescribed FOXK1::GRHL1/2 or GPS2::GRHL1/2/3 in-frame fusion transcripts. Microscopic examination of a preliminary set of five cases revealed well-delimitated tumours located in the dermis with frequent extension to the subcutaneous tissue. Tumours presented a massive and nodular architecture and consisted of a proliferation of basaloid cells. A biphasic pattern sometime resulting in tumour cell nests ('cell balls') was present. Immunohistochemistry demonstrated the expression of cytokeratins (CKs) 15, 17, and PHLDA1. In addition, numerous CK20-positive Merkel cells were detected. RNA sequencing (RNA-seq) revealed a FOXK1::GRHL1 chimeric transcript in three cases and a FOXK1::GRHL2 fusion in two cases. In a second series for validation (n = 88), FOXK1::GRHL1/2 fusion transcripts were detected by RT-qPCR or FISH in an additional 12 trichogerminomas and not in any other follicular tumour entities or basal cell carcinoma cases (n = 66). Additional RNA-seq analysis in trichogerminoma cases without detected FOXK1::GRHL1/2 rearrangements revealed GPS2::GRHL1 fusion transcripts in two cases, GPS2::GRHL2 in one case, and GPS2::GRHL3 fusion transcript in one case. Therefore, our study strongly suggests that GRHL1/2/3 gene rearrangements might represent the oncogenic driver in trichogerminoma, a subset of follicular tumours characterized by immature features and numerous Merkel cells. © 2022 The Pathological Society of Great Britain and Ireland.

[Extra Mammary Paget disease]. / Maladie de Paget extra-mammaire.

Extramammary Paget's disease is a rare malignancy. The underlying cause of VPD remains not well understood. We provide an overview of the histopathology of vulvar Paget's disease, with or without invasion.

[Multifocal vulvar pigmentation: Don't ignore a rare diagnosis]. / Pigmentation vulvaire multifocale : ne pas méconnaître un diagnostic rare.

Vulvar melanoma is a rare tumour, of poorly known pathogenesis, which presents particularities compared to cutaneous melanoma: more frequently achromic and very often multifocal, it is of the lentiginous histological type (MLM), with in half of the cases lentiginous melanocytic hyperplasia at a distance.

[Diagnosis of pigmented lesions of the vulva]. / Diagnostic des lésions pigmentées de la vulve.

This article presents the different pigmented lesions of the vulva (PLV) that are systematically found in 8 to 12% of women and are most often ignored. The histological aspect of physiological pigmentation and its modifications due to hormonal impregnation should be known by pathologists in order to better understand the very large variety of lesions.

[A vulvar verruciform xanthoma]. / Un xanthome verruciforme vulvaire.

We report a case of a vulvar verruciform xanthoma. Verruciform xanthoma is a rare benign lesion that occurs most commonly on the oral and genital mucosa. Under the microscope, this lesion displays acanthotic papillary epidermis with parakeratosis that extends deep into the epithelium, elongated rete ridges and xanthomatous cells in the papillary dermis. Vulvar lesions almost always occur in a local pathological context (lichen planus or sclerosus). It is important to be aware of this entity as it can mimic squamous carcinoma.

[Vulvar intraepithelial neoplasias]. / Les néoplasies intraépithéliales vulvaires.

Vulvar squamous cell carcinoma arises from precursor lesions: vulvar intraepithelial neoplasias (VIN). Most of them are caused by the human papillomavirus (HPV), and the precursor lesion for this group is VIN usual type/high grade squamous intraepithelial lesion (uVIN/HSIL) of variable clinical presentation and having a light invasive potential. Some VIN are HPV-independent and arise in older women against the background of chronic dermatoses, mostly lichen sclerosus. Their histological diagnosis is more subtle. They have a higher invasive potential. A third precursor, leading to well-differentiated, or even verrucous, carcinomas, is still ill-defined to this day. We detail these lesions' clinics, histology, and biomarkers (immunohistochemical and molecular).

[Vulva anatomopathological peculiarities]. / Particularités anatomo-pathologiques de la vulve.

The vulva is the transition zone between the skin and the lower genital tract. As such, it presents histological specificities, comprises physiological modifications which are specific to it and is characterized by particular artifacts. Knowledge of them prevents many questions or even diagnostic errors.

Retrospective Outcome Analysis of 39 Patients Who Underwent Lip Surgery for Cutaneous Carcinoma.

PURPOSE: The treatment of lip carcinomas needs tumor surgical resection with safety margins respect. The aim of this study was to report the oncologic and aesthetic/functional outcomes of a retrospective monocentric case series of 39 patients treated for cutaneous lip cancer. METHODS: This retrospective study assessed 56 patients who were treated for a lip carcinoma between 2008 and 2012 and included 39 patients with cutaneous lip basal cell carcinoma or squamous cell carcinoma. Clinical, surgical and pathological data were reviewed, and patients were interviewed for follow-up data. A comparison was made between the marked surgical margins and the margins observed under microscopy after histologic process. RESULTS: The most frequent tumor type was basal cell carcinoma in 69.2 %. The measured surgical margins were superior to the histological margins in 24 cases (61.5 %) and were inferior in 13 cases (33.3 %). Overall survival and recurrence-free survival rates at 1 year were 97.5 and 95 % respectively. CONCLUSION: Differences between the surgical margins and the final histologic margins were the main finding of this retrospective study. These differences were attributed to surgical practices and modification during the histological process. Nevertheless, we did not observe a higher rate of recurrence or death in our study than in literature.

Vulvar hidradenoma papilliferum (HP) is located on the sites of mammary-like anogenital glands (MLAGs): Analysis of the photographs of 52 tumors.

BACKGROUND: Hidradenoma papilliferum (HP) is a benign tumor that primarily affects the anogenital area of adult women. Previously considered apocrine tumors, anogenital HP tumors are now interpreted as adenomas of mammary-like anogenital glands based on their histologic features. OBJECTIVE: This clinical study was undertaken to determine whether vulvar HP is located on mammary-like anogenital gland sites and to describe its morphologic features. METHODS: The clinical photographs of 52 histologically confirmed vulvar HP provided by 7 vulva specialists were analyzed. RESULTS: In all, 90.4% of the HP were located on the interlabial sulcus, adjacent zone, or the perineum. These tumors were polymorphous in terms of number (1 or multiple), size (<1-4.5 cm), color (pink, red, blue), surface (ulcerated or not), and architecture (unilobular or multilobular). LIMITATIONS: Eight histologic reports could not be reviewed by the authors but the contributors confirmed that the photographs sent were only those of histologically confirmed HPs. CONCLUSIONS: Vulvar HP is mainly located on mammary-like anogenital gland sites, thereby providing further evidence to their histogenesis. Although a nonulcerated or ulcerated tumor of the interlabial sulcus should evoke a HP diagnosis, the latter must be confirmed histologically.

Histopathologic and Ultrastructural Features of Gold Thread Implanted in the Skin for Facial Rejuvenation.

The authors report the histopathologic and ultrastructural features of gold threads, which were implanted in the cheek subcutis of a 77-year-old woman 10 years ago. These particles did not give rise to any adverse reactions and were fortuitously discovered by the surgeon during a facelift. Histopathology showed a nonpolarizing exogenous material consisting of black oval structures surrounded by a capsule of fibrosis and by a discrete inflammatory reaction with a few giant cells. In some cases, only a long fibrous tract surrounded by a moderate mononucleate infiltrate was observed. The wires were characterized with scanning electron microscopy, and X-ray microanalysis revealed a specific peak at 2.2 keV representative of gold that was absent in the control skin sample. As this value is specific for gold, it confirms the presence of the metal in the patient's skin. The histopathologic appearance of gold threads is particularly distinctive and easily recognizable by dermatopathologists.

Unilateral vulval swelling in cyclists: a report of 8 cases.

OBJECTIVE: To define the clinical features, imaging results, histopathologic patterns, and clinical outcomes seen in patients who develop vulval swelling as a result of intensive cycling. METHODS: The case notes of 8 female cyclists were retrospectively reviewed. RESULTS: The mean age of the patients was 45 years, and all were cycling long distances each week (range, 125-450 km; median, 210 km). All patients had a unilateral swelling of the labium majus. Five patients had magnetic resonance imaging showing asymmetry of the vulva with no enhanced signaling associated with inflammation. Histologic examination in 3 cases revealed dermal fibrosis and dermal edema associated with dilatation of lymphatic vessels. In 1 case, a perifollicular inflammatory infiltrate containing epithelioid granulomas was seen but Crohn's disease was excluded. In another case, fibromuscular hyperplasia was seen. Six patients had surgical excision of the swollen area, and 4 patients were able to resume cycling without problems up to 5 years of follow-up. The cosmetic appearance was initially considered satisfactory by 5 patients. However, 2 patients required a second surgical procedure to further improve the cosmetic appearance. In 1 case, there was a postoperative hematoma followed by an immediate recurrence of the swelling, which persisted. CONCLUSIONS: Unilateral swelling of the labium majus occurring in cyclists can be related to dermal fibroedema associated with lymphatic dilatation or to an increase in adipose tissue. Surgical results were satisfactory in 5 of the 6 patients who underwent excision.

Vascular invasion and other invasive features in granular cell tumours of the skin: a multicentre study of 119 cases.

BACKGROUND: Incidental finding of vascular invasion has been described in some benign granular cell tumours. Malignancy in granular cell tumours is excessively rare and its assessment relies on necrosis and cytological criteria. AIMS: To assess histopathological invasive features, particularly vascular invasion, in a large series of granular cell tumours of the skin. METHODS: 119 granular cell tumours of the skin were collected in 114 patients between 2001 and 2011. Histopathological and epidemiological data were collected. Five step sections and one orcein staining were performed in all cases. RESULTS: Mean age of the patients was 43.7±18 years. Granular cell tumours were multiple in 7% of patients. They were classified as benign in 111 cases, and atypical in eight cases. No malignant granular cell tumour was present. Tumours had 1.48±1.3 cm mean diameter, showed peripheral invasive growth pattern in 71% of cases, had a mean depth of 8.8±4.7 mm, and reached the subcutis in 66% of cases. Infiltration of arrector pili muscle occurred in 23% (95% CI 16% to 32%), and perineural spread in 66% (95% CI 56% to 74%) of cases. Vascular invasion occurred in 23% (95% CI 16% to 32%) of cases, with subendothelial layers infiltration or vascular obliteration. No intraluminal embolus was found. No association was found between vascular invasion and clinical outcome. CONCLUSIONS: Histopathological features of local invasion are frequent in otherwise benign granular cell tumours. Vascular invasion consists of an infiltration of the subendothelial layers, without intraluminal cells, and may not be considered as a marker of adverse prognosis.

Foreign body reaction to Radiesse: 2 cases.

We report 2 cases of a foreign body reaction to Radiesse, a semipermanent soft-tissue filler consisting of 30% calcium hydroxylapatite microspheres and 70% carboxymethyl cellulose gel carrier. In one case, injection of this filler provoked a nodule on the columella, which was discovered during rhinoplasty. In the second case, the reaction was revealed during histopathologic examination of the deep section of a surgically removed basal-cell carcinoma. Histopathology showed a foreign body reaction with numerous giant cells and histiocytes, some plasma cells, and lymphocytes. Within this inflammatory reaction, a nonpolarizing exogenous material was identified consisting of numerous, round, uniformly sized, yellowish, extracellular deposits with a crackled appearance. Although many authors claim that Radiesse does not induce any foreign body reactions, we found a number of similar histopathologic pictures in studies describing animal or human auricular area test sites or even in reports of lip nodules, which are a well-known adverse effect after injection of this filler into this site. The histopathologic appearance of Radiesse is particularly distinctive and easily recognizable by dermatologists and dermatopathologists.

Anti-HPV16 E2 protein T-cell responses and viral control in women with usual vulvar intraepithelial neoplasia and their healthy partners.

T-cell responses (proliferation, intracellular cytokine synthesis and IFNγ ELISPOT) against human papillomavirus 16 (HPV16) E2 peptides were tested during 18 months in a longitudinal study in eight women presenting with HPV16-related usual vulvar intraepithelial neoplasia (VIN) and their healthy male partners. In six women, anti-E2 proliferative responses and cytokine production (single IFNγ and/or dual IFNγ/IL2 and/or single IL2) by CD4+ T lymphocytes became detectable after treating and healing of the usual VIN. In the women presenting with persistent lesions despite therapy, no proliferation was observed. Anti-E2 proliferative responses were also observed with dual IFNγ/IL2 production by CD4+ T-cells in six male partners who did not exhibit any genital HPV-related diseases. Ex vivo IFNγ ELISPOT showed numerous effector T-cells producing IFNγ after stimulation by a dominant E2 peptide in all men and women. Since the E2 protein is absent from the viral particles but is required for viral DNA replication, these results suggest a recent infection with replicative HPV16 in male partners. The presence of polyfunctional anti-E2 T-cell responses in the blood of asymptomatic men unambiguously establishes HPV infection even without detectable lesions. These results, despite the small size of the studied group, provide an argument in favor of prophylactic HPV vaccination of young men in order to prevent HPV16 infection and viral transmission from men to women.