Vulvar Lesions Research Articles

Presencia de formas amastigotes de Leishmania sp en lesiones de glándulas inguinales en perras

Leishmaniasis is considered public health matter, where the interaction of several factors affects a significant amount of species. It is a chronic disease, which has as vector the Lutzomyia mosquito, inoculating the parasite Leishmania sp in the hosts when in its blood supply, this disseminated rapidly, taking advantage of immunosuppression and parasitizing previously unreported tissues. In this case report will be described the involvement by the parasite in the tissues of the mammary lesions, in a dog of 4 years, presenting vulvar swelling and lesions in the inguinal breasts. Tests were performed as a hemogram and biochemical profile, complementing with oncological cytologies of lesion sites. Some changes were observed as normocytic normochromic anemia, hyperproteinemia, and the concomitant presence of the parasite Hepatozoon canis, both in the blood and cytologic smear. In the cytologic smear, it was verified the compatibility with the Canine Transmissible Venereal Canine tumor (TVTC) and the mammary lesion, an inflammatory process, with pleomorphism, atypias, large amount of neutrophils and macrophages parasitized by amastigotes forms of Leishmania sp. The involvement of the parasite in tissues not yet reported, shows that it is opportunistic, use immunosuppression to spread more quickly, and a more careful investigation of the lesions present in the patients is necessary.

Aggressive angiomyxoma of the vulva: a case report in a Brazilian patient

Aggressive angiomyxoma is a locally aggressive tumor of mesenchymal origin. The condition predominantly affects females, with a male/female ratio of 6:1. Most cases occur during the reproductive years, with a peak between the third and fourth decades of life. The symptoms are non-specific, and the principal differential diagnosis is with Bartholin’s cysts or abscesses. The treatment of choice is surgical excision of the lesion, including evaluation of the margins. This case report refers to a 41-year old patient with an insidiously growing lesion on the right vestibular area measuring approximately 9 x 5 x 5 cm, associated with dyspareunia. Surgical excision was successful, and there have been no signs of tumor recurrence in the six months of follow-up. Differential diagnosis in cases of vulvar lesions is of the utmost importance. A detailed vulvar examination is essential to ensure early diagnosis and to reduce the rate of underdiagnosed cases of aggressive angiomyxoma

Immunotherapy With E7 T Cell Receptor T Cells for Vulvar High-Grade Squamous Intraepithelial Lesions

Immunotherapy With E7 T Cell Receptor T Cells for Vulvar High-Grade Squamous Intraepithelial Lesions

Relationship between vulvar symptoms and incidence of vulvar cancer in women referred to a rapid access clinic.

We performed a study to estimate incidence of vulvar cancer in women with vulvar symptoms (irritation, pain, bleeding +/- presence of lesion) referred to a secondary care, rapid-access clinic. Prospective data collection of all direct referrals from a primary to a secondary care gynecological oncology clinic from 2011 to 2016, for women with suspicious vulvar symptoms. 32/393 (8.1%) women had vulvar cancer, and 24/393 (6.1%) had a premalignant lesion. Multivariate logistic regression showed that women referred without a specific lesion had considerably lower odds of a diagnosis of vulvar cancer than those with a lesion (OR=0.11, 95% CI: 0.03-0.49). In total, 30/234 (12.8%) women with a vulvar lesion (mass or ulcer), had vulvar cancer, compared with 2/159 (1.3%) of those referred without a lesion (these patients had vulvar irritation and bleeding but had a visible lesion on examination). None of the 140 women with irritation alone, in the absence of a visible lesion or bleeding, had pre-invasive disease or cancer. Presence of a vulvar lesion, especially if painful/bleeding, has a high positive predictive value for vulvar cancer and 12.8% of women presenting with any vulvar lesion to secondary care had cancer.

Effect of Human Papillomavirus Vaccine to Interrupt Recurrence of Vulvar and Anal Neoplasia (VIVA)

Human papillomavirus (HPV), particularly HPV type 16, causes most anal and vulvar high-grade squamous intraepithelial lesions (HSIL), which are precursors to cancer. After initial treatment of HSIL, more than 30% of patients will have disease recurrence, with even higher recurrence among HIV-positive individuals and men who have sex with men. Recurrences can be debilitating and lead to significant morbidity and medical expense. Observational studies suggest a possible therapeutic benefit of the licensed HPV vaccines in reducing recurrent lesions in previously infected persons. To test whether the licensed prophylactic HPV vaccine (Gardasil-9) can reduce the risk of HSIL recurrence by 50% in previously unvaccinated individuals recently treated for anal or vulvar HSIL. This is a trial protocol for a randomized, double-blind, placebo-controlled, proof-of-concept clinical trial. Eligible participants are aged 27 to 69 at study start and have not received prior HPV vaccination, have had anal or vulvar HSIL diagnosed on or after January 1, 2014, and have no evidence of HSIL recurrence at screening. Persons infected with HIV are eligible for the study provided they are receiving antiretroviral therapy. Target enrollment is 345 individuals. The primary outcome is time to histopathologically confirmed recurrence of HSIL. Differences in the risk for recurrence of HSIL will be evaluated using Cox proportional hazard models. Additional analyses include (1) frequency of HSIL recurrence; (2) role of HPV antibodies in deterring recurrence; (3) role of HPV persistence in recurrence, as measured by HPV genotype or HPV-16 variant lineage determined using swab samples collected at months 0, 18, and 36; and (4) incidence of adverse events. The study will be conducted at the University of Washington Virology Research Clinic from 2017 through 2022. Participants will be followed up for up to 36 months in the clinic, and up to 42 months by telephone. Management of persistent or rapidly recurring anogenital HSIL remains challenging. Results from this study will provide evidence on whether incorporating the nonavalent HPV vaccine into routine care can decrease recurrence of anal and vulvar HSIL. ClinicalTrials.gov identifier: NCT03051516.

Adolescent Vulvar Angiokeratoma Associated with Lichen Sclerosus.

We present an adolescent with multiple vulvar angiokeratomas within a background of lichen sclerosus. A 13-year-old girl presented with vulvar pruritus and wart-like vulvar lesions. Four lesions were resected because of discomfort and uncertainty of the diagnosis. Pathology revealed angiokeratomas with chronic inflammation suggestive of lichen sclerosus. Postoperatively, pruritus continued in the largest excised lesion, which was associated with lichen sclerosus, and symptoms were treated successfully with topical steroids. Vulvar angiokeratomas are asymptomatic red papular lesions and are rare in the female adolescent population. In this case, the pathology revealed the rare co-occurrence of angiokeratomas and lichen sclerosus. Biopsies of vulvar vascular lesions in symptomatic adolescents are recommended. Vulvar angiokeratomas might manifest rare genetic disease in otherwise asymptomatic female patients and warrant further follow-up.

Mucinous Metaplasia of the Vulva in Zoon Vulvitis and Lichen Sclerosus et Atrophicus. Description of 3 Additional Cases of a Rarely Reported Histopathologic Finding

Mucinous metaplasia of the vulva (MMV) is a histopathologic finding that has been reported previously in only 3 patients and needs to be distinguished from vulvar extramammary Paget disease. We report 3 additional instances of MMV associated to Zoon vulvitis and vulvar lichen sclerosus et atrophicus. Histochemical and immunohistochemical studies were performed on biopsies from erythematous and erosive vulvar lesions of 3 women aged 64, 80 and 84 years, with features of Zoon vulvitis (2 cases) and lichen sclerosus et atrophicus (1 case). Mucin-containing epithelial cells were present on the uppermost layers of the squamous epithelium. On immunohistochemical study the metaplastic cells were positive for cytokeratin 7, epithelial membrane antigen and carcinoembryonic antigen, thus mimicking the phenotype of Paget disease. MMV is most likely related to chronic inflammation. Cytological and architectural features allow for distinction from Paget disease because the mucin-containing cells of mucinous metaplasia of the vulva lack atypia and are predominantly located on the most superficial layers of the surface epithelium.

Extensive Squamous Metaplasia in Hidradenoma Papilliferum of Vulva: Illusion of Squamous Cell Carcinoma

Hidradenoma papilliferum is a rare, slow-growing, benign, cystic, papillary tumour occurring in middle-aged females, in the anogenital region commonly. It involves the anogenital mammary-like glands and is usually asymptomatic. Simple excision is curative. We present a case of hidradenoma papilliferum of long-standing duration with extensive squamous metaplasia. A post-menopausal lady presented with an exophytic growth on the left labia majora and part of mons pubis. It was initially misdiagnosed on the basis of vulvar biopsy and managed as squamous cell carcinoma of the vulva. The final histopathology revealed an epithelial tumour involving the vulva with extensive squamous metaplasia. The tumour involved mainly the dermis and the subcutaneous tissue. This is the first case in the literature where the diagnosis of hidradenoma papilliferum was confused with squamous cell carcinoma of the vulva due to its clinical presentation and extensive squamous metaplasia. Diagnosis of hidradenoma papilliferum should be kept in mind if a woman presents with vulval papillary or nodular lesions. An expert clinical and histopathological review should be done to avoid misdiagnosis.

Zoon's vulvitis and importance of histology in diagnosis of benign vulvar lesions in outpatient setting

Zoon's vulvitis and importance of histology in diagnosis of benign vulvar lesions in outpatient setting

Medical treatment as a possible treating modality for premalignant vulvar lesions

Purpose of investigation: Purpose of this investigation was to determine the possibilities of non-surgical, medical treatment of high-grade squamous intraepithelial lesion (HSIL) of the vulva and differentiated type of vulvar intraepithelial lesions (VIN) and to determine the effect of medical treatment by local and systemic immunomodulators in relation to different histological types. Materials and Methods: The study included five patients with different histological types of VIN. The patients were given: systemic immunomodulator and antivirotics. After that, the patients initially included in the study were followed for a year, while the follow-up of the older patients group is still ongoing, and it has been six months since the completion of the treatment. Results: Combined medical therapy has positive therapeutic effect in the treatment of young HPV-positive adolescent patients with HSIL of the vulva. Medical treatment in HPV negative women with differentiated type VIN is less efficient, achieving partial remission in only 33% of patients. Conclusion: Combined medical therapy achieved better effects in hyperpigmented multifocal type of VIN.

Clinical and molecular classification of vulvar squamous pre-cancers.

Vulvar intraepithelial neoplasia (VIN) is a precursor to vulvar squamous cell carcinoma and is defined histopathologically by the presence of atypia. VIN has been classified into two types: usual vulvar intraepithelial neoplasia (uVIN), which is also referred to as a vulvar high-grade squamous intra-epithelial lesion (HSIL), and differentiated VIN (dVIN). The former is associated with chronic infection by sub-types of the human papilloma virus (HPV), whereas dVIN is HPV-independent and frequently associated with lichen sclerosus. The distinction is important because dVIN has a greater risk of, and more rapid transit to, vulvar squamous cell carcinoma. Furthermore, dVIN-associated vulvar cancers have an increased risk of recurrence and higher mortality than those arising from HSIL. Molecular characterization of vulvar squamous cell carcinoma precursors using next-generation sequencing is a relatively novel, but rapidly advancing field. This review appraises recent studies that have investigated the risks of progression to vulvar malignancy associated with HSIL and dVIN, the prognosis of HPV-dependent and HPV-independent vulvar squamous cell carcinomas, and conducted next generation sequencing mutation analyses to elucidate the genomic profiles underlying VIN. These studies suggest that HSIL and dVIN are characterized by different underlying molecular alterations that may have important implications for treatment and follow-up of women diagnosed with vulvar squamous cell cancer.

Recurrence of endometrial carcinoma presenting as vulvar lesions.

Vulvar metastasis is an unusual presentation of recurrent endometrial cancer and should be part of the differential diagnosis of vulvar lesion.

Detection of pagetoid urothelial intraepithelial neoplasia extending to the vagina by cervical screening cytology: a case report with renewed immunochemical summary

BackgroundPagetoid spread of urothelial carcinoma (UC) to the lower genital tract is quite a rare and diagnostically challenging condition. Pagetoid urothelial intraepithelial neoplasia extending to the vagina is difficult to diagnose, especially in remote recurrences without symptomatic or macroscopic lesions typical to Paget disease. However, its identification by cervical screening cytology is important because UC is often characterized by a long history of relapse.Case presentationA 68-year-old Japanese postmenopausal woman developed brown vaginal discharge after radical cystectomy for bladder cancer (high-grade UC, pT2a pN0 cM0 [Union for International Cancer Control, 8th edition]) concomitant with focal in-situ UC in the urethra. She had a history of left renal pelvis UC, which was surgically removed 9 months before the radical cystectomy. Gynecologic examination of the lower genital tract was unremarkable although cervical screening cytology demonstrated severely atypical cells with pleomorphism repeatedly. Cervical colposcopy and diagnostic conization revealed no cervical neoplasm. In retrospect, immunocytochemical p16/Ki-67 dual staining for the previous cervical screening was negative for p16 labeling, and the neoplastic cells were positive for cytokeratins 7 and 20, p63, and GATA binding protein 3. No high-risk human papillomavirus genotype was identified by an automated DNA chip system using liquid-based cytology samples. Eleven months post-cystectomy, punch biopsy of the vulva and vagina confirmed intraepithelial UC in the juxtaposed squamous epithelium with pagetoid spread demonstrating positivity for specific urothelial markers: uroplakins II and III and thrombomodulin. Concurrent invasive malignancy was ruled out, and CO2 laser vaporization of the vulvar and vaginal lesion was performed. The patient remained alive without evidence of invasive malignancy for 14 months after the radical cystectomy for bladder cancer.ConclusionsTo detect recurrent pagetoid urothelial intraepithelial neoplasia with pagetoid spread in the lower genital tract, pathologists should recognize the history of prior UC with special attention to absence of p16 labeling in cervical cytology as a pointer to the diagnosis of urothelial cancer. Using further biopsy and immunohistochemical confirmation of UC relapse, investigation to rule out invasive malignancies and careful follow-up throughout the patient’s lifetime is recommended.

Test-retest reliability of the Welfare Quality Assessment protocol for pigs applied to sows and piglets. Part 2. Assessment of the principles good feeding, good housing, and good health1.

The present study aimed at testing the feasibility and on-farm test-retest reliability of the Welfare Quality Assessment protocol for pigs applied to sows and piglets. The study was conducted on 13 farms in Northern Germany, which were visited 5 times by the same observer, and included 2 experimental setups: first, the complete Welfare Quality Assessment protocol for sows and piglets was applied to the farms. Second, additional assessments in the gestation unit considered all sows. The complete protocol assessments were used to evaluate the feasibility of the protocol. Furthermore, the data were analyzed with regard to on-farm test-retest reliability. The present publication focuses on the Welfare Quality principles good feeding, good housing, and good health, which are based on individual indicators (IN). The second experimental setup was utilized to verify the test-retest reliability of IN in the gestation unit with an increased number of animals under assessment. The test-retest reliability was calculated using Spearman's rank correlation coefficient (RS), intraclass correlation coefficient (ICC), smallest detectable change (SDC), and limits of agreement (LoA). Farm visit 1 (F1; day 0) was set as a reference and compared with farm visits 2 to 5 (F2 to 5; day 3, week 7, month 5, month 10). The IN of the above-named Welfare Quality principles achieved mostly acceptable test-retest reliability (e.g., wounds on the body F1 to F4: RS 0.34 to 0.57, ICC 0.40 to 0.41, SDC 0.02 to 0.12, LoA [-0.03; 0.02] to [-0.09; 0.14]) in terms of the on-farm test-retest reliability. Poor test-retest reliability was detected for body condition score concerning the principle good feeding, for bursitis and panting in sows and for huddling and panting in piglets within the principle good housing, and finally for vulva lesions, metritis, and local infections in sows and for scouring and lameness in piglets in the principle good health. Variations among the farm visits, which resulted in poor test-retest reliability, may be explained by seasonal effects (panting), moving animals (bursitis, lameness, huddling), rare occurrences of diseases (metritis, local infections, scouring), and differently conditioned sow groups (body condition score). The second experimental setup confirmed the results for IN in the gestation unit. Thus, the reported test-retest reliability determines the Welfare Quality Assessment protocol for sows and piglets to be a reliable approach to assess welfare in sows and piglets.

Tumor cell-specific Serpin A1 expression in vulvar squamous cell carcinoma

PurposeThe two main etiological factors for vulvar squamous cell carcinoma (vSCC) are the vulvar dermatosis lichen sclerosus (LS) and high-risk human papillomavirus (hrHPV). Serpin A1 (α1-antitrypsin) is a serine protease inhibitor, which plays a role in the tumorigenesis of various cancer types. The aim of the study was to evaluate the expressions of Serpin A1 in LS, premalignant vulvar lesions, and vSCC using immunohistochemistry (IHC) and serum analysis, and to compare Serpin A1 stainings to the tumor markers p53 and p16.MethodsIn total, 120 samples from 74 patients were studied with IHC for Serpin A1, p53 and p16: 18 normal vulvar skin, 53 LS, 9 premalignant vulvar lesions (dVIN/HSIL) and 40 vSCC samples. Serum concentrations of Serpin A1 were analyzed from 30 LS, 44 vSCC and 10 control patients. Expressions were compared to clinical data.ResultsTumor cell-specific Serpin A1 overexpression was detected in 88% of vSCC samples, independent of the etiology. The intensity of Serpin A1 expression was significantly higher in vSCC than in healthy vulvar skin, LS, or premalignant vulvar lesions. Serpin A1 showed an association with p53 positivity. No difference in overall survival was found between Serpin A1-, p53-, or p16-positive vSCC patients. Serum concentrations of Serpin A1 were equal in the LS, vSCC, and control groups.ConclusionTumor cell-specific Serpin A1 overexpression is a potential biomarker in vSCC.

Hidradenoma papilliferum of the vulva with extensive squamous metaplasia mimicking malignancy: Rare entity with diagnostic challenge

Hidradenoma papilliferum (HP) is an uncommon benign cutaneous adnexal neoplasm of the anogenital region commonly seen in middle-aged, Caucasian females. Anastomosing and branching tubules, lined by columnar cells, and a basal layer of myoepithelial cells are the characteristic histopathological features. We report a case of HP in a 60-year-old female presented with a vulvar lesion. The case was evaluated for malignancy, with the initial histopathology showing extensive squamous metaplasia but ultimately found to have HP.

Histopathologic spectrum of vulvar lesions in South India with an emphasis on morphological classification of vulvar squamous cell carcinoma: a retrospective study of 8 years

Background Vulvar diseases comprise inflammatory and neoplastic conditions. Comprehensive data in Indian population is lacking. Vulva is also prone to HPV related lesions and the prevalence of HPV related vulvar squamous cell carcinoma (SCC) in the study population is not known. Objectives The primary aim of this study was to describe the range of vulvar lesions over a period of 8 years in South Indian population. Additionally the vulvar squamous neoplasias were subclassified into morphological types in an attempt to differentiate the HPV and non HPV associated lesions, which helps in triaging cases for HPV testing. Methods The vulvar lesions from database were categorised as inflammatory, cysts, non-neoplastic proliferations and neoplasms. The inflammatory lesions were classified as lichenoid and acanthotic patterns. The squamous neoplasias were morphologically categorised into HPV and non HPV associated types. Results There were 204 biopsies from 192 adults and 10 children. Epithelial ones were commoner than mesenchymal (48 vs.18). Benign adnexal neoplasms included hidradenoma papilliferum, syringoma , apocrine adenoma. The commonest malignancy was squamous cell carcinoma (SCC) (n=21) of which 17 were classified as HPV associated and 4 non-HPV associated. SCC subtypes were warty (n=3), basaloid (n=5), mixed (n=1) and arising from differentiated VIN(n=8). One case of basal cell carcinoma was reported. There were 15 cases of VIN [5 LSIL and 10 HSIL {3 warty, 5 basaloid,2 mixed}], one extramammary Paget’s disease. Vascular neoplasms were the commonest mesenchymal lesions. There was one case each of leiomyosarcoma and angiosarcoma. Among non-neoplastic proliferations, fibroepithelial polyps were the commonest (n=9). Lichenoid inflammatory lesions (n=75) was more common than acanthotic (n=4). Conclusion The study highlights the importance of histopathologic typing of SCC and VIN, which helps in triaging cases for HPV testing in resource limited setting.

Idiopathic lymphoplasmacellular mucositis of the vulva in a patient with partial interferon-γ receptor 1 deficiency

We report a case of idiopathic lymphoplasmacellular mucositis (ILPM) of the vulva in a 48-year-old woman with partial interferon-γ receptor 1 (IFN-γR1) deficiency. The lesion had an unusual ulcerovegetative presentation. Remarkable response was observed with oral and topical steroids in the first 3 weeks. However, the lesion recurred after tapering oral steroids and continuous low-dose oral steroids were required to suppress recurrence. To the best of our knowledge, this is the first case report of ILPM in a patient with partial IFN-γR1 deficiency. ILPM should be included in the differential diagnosis of persistent vulvar ulcerovegetative lesions.

Secondary healing strategy for difficult wound closure in invasive vulvar cancer: a pilot case-control study

OBJECTIVES:Despite the number of surgical advances and innovations in techniques over time, radical vulvectomy frequently results in substantial loss of tissue that cannot be primarily closed without tension, the mobilization of surrounding tissues or even the rotation of myocutaneous flaps. The aim of this study was to evaluate the feasibility of leaving the surgical vulvar open wound for secondary healing in situations where primary closure of the vulvar wound is not possible.METHODS:This case-control pilot study analyzed 16 women with a diagnosis of squamous cell carcinoma of the vulva who first underwent inguinofemoral lymphadenectomy, 6-week sessions of chemotherapy and 25 daily sessions of radiotherapy. Afterward, excision of the vulvar lesion with free margins was performed between January 2011 and July 2017. Twelve patients underwent primary closure of the wound (control), and in 4 patients, the surgical wound was left open for secondary healing by means of a hydrofiber (case). The inclusion criteria were a) FIGO-2009 stage II up to IIIC; b) squamous cell carcinoma; and c) no evidence of pelvic or extrapelvic disease or pelvic nodal involvement. The exclusion criteria were extrapelvic disease or pelvic nodal involvement, another primary cancer, or a poor clinical condition. ClinicalTrials.gov: NCT02067052.RESULTS:The mean age of the patients at the time of the intervention was 62.1. The distribution of the stages was as follows: II, n=6 (37 %); IIIA, n=1 (6%), IIIB, n=1 (6%) and IIIC, n=8 (51%). The mean operative time was 45 minutes. The hospital stay duration was 2 days. Full vulvar healing occurred after an average of 30 days in the control group and after an average of 50 days in the case group.CONCLUSION:A secondary healing strategy may be an option for the treatment of vulvar cancer in situations of non-extensive surgical wounds when primary closure of the wound is not possible.

Atrophic vulvar lichen sclerosus evolving to an epidermoid carcinoma: about an uncommon case

Malignant tumors of the vulva are usually budding, ulcerated, or infiltrating. The fear of cancer must always be in mind, in front of any vulvar lesion. Therefore, do not hesitate to make biopsies of any lesion of the vulva to confirm or deny a cancer. We hereby report the uncommon case of a postmenopausal 68-old-patient followed for an atrophic vulvar lichen sclerosus which eventually transformed into an epidermoid carcinoma of the vulva. The indication for right hemivulvectomy with sentinel lymph node procedure was retained. Vulvar cancer takes a variety of aspects. It is therefore necessary to always have it in mind and to make a biopsy before any suspicious lesion. Since the atrophic vulvar lichen sclerosus of the vulva is a pre-cancerous lesion, we believe that its follow-up must be strict and a second biopsy must be performed before any worsening of the lesions. Finally, the procedure of the sentinel lymph node is of great interest when we know the morbidity of the inguinal region dissections but also the slow learning curve of surgical techniques of vulvar cancer.