Differentiated Vulvar Intraepithelial Neoplasia: What Criteria Do We Use in Practice?

OBJECTIVES: We sought to recognize the working diagnostic criteria for differentiated vulvar intraepithelial neoplasia (dVIN) among expert pathologists in the field. We also sought the frequency of definitive diagnosis, terminology of equivocal lesions, and views on dVIN's biological significance. METHODS: Respondents ranked 26 histological and 8 ancillary studies and 5 clinical findings as "essential," "nonessential but strongly supports diagnosis," "possibly supports diagnosis," "weighs against diagnosis" or "uncertain significance or noncontributory." Consensus was defined as 75% agreement. They were asked about diagnosing dVIN on partially sampled lesions, terminology for uncertain lesions, frequency of diagnosis of dVIN relative to uncertain lesions, and if dVIN a is a precursor to an invasion. RESULTS: Twenty-three completed the survey. Only "basal layer atypia" met consensus (86%) as essential. Consensus criteria for being at least strongly supportive of dVIN were "basal layer hyperchromasia," "presence of basal layer mitoses," and "large keratinocytes with abundant eosinophilic cytoplasm." Only "block-like positivity with p16" or positive HPV specific studies weighed against the diagnosis by consensus. Approximately 87% diagnosed dVIN on partially sampled lesions. Squamous cell hyperplasia with atypia was the most frequent terminology used for uncertain lesions; 87% felt dVIN is a precursor to invasion. CONCLUSIONS: Only basal layer atypia was considered diagnostically essential by consensus. Additional criteria that strongly support the diagnosis include changes affecting the basal layer and abundant eosinophilic keratinocytic cytoplasm. There was no consensus on ancillary study findings to confirm dVIN. Most would diagnose dVIN on a partial sample. Most consider dVIN a precursor to invasion.

The 2015 International Society for the Study of Vulvovaginal Disease (ISSVD) Terminology of Vulvar Squamous Intraepithelial Lesions.

OBJECTIVES: The impact of terminology for vulvar intraepithelial lesions has been significant over the years, because it has affected diagnosis, treatment, and research. The introduction of the Lower Anogenital Squamous Terminology (LAST) in 2012 raised 2 concerns in relation to vulvar lesions: firstly, the absence of reference to "differentiated vulvar intraepithelial neoplasia" (differentiated VIN) could lead to its being overlooked by health care providers, despite its malignant potential. Secondly, including the term "low-grade squamous intraepithelial lesion" (LSIL) in LAST recreated the potential for overdiagnosis and overtreatment for benign, self-limiting lesions. MATERIALS AND METHODS: The International Society for the Study of Vulvovaginal Disease (ISSVD) assigned the terminology committee the task of developing a terminology to take these issues into consideration. The committee reviewed the development of terminology for vulvar SILs with the previous 2 concerns in mind and reviewed several new terminology options. RESULTS: The final version accepted by the ISSVD contains the following:•Low-grade SIL of the vulva or vulvar LSIL, encompassing flat condyloma or human papillomavirus effect.•High-grade SIL or vulvar HSIL (which was termed "vulvar intraepithelial neoplasia usual type" in the 2004 ISSVD terminology).•Vulvar intraepithelial neoplasia, differentiated type. CONCLUSIONS: The advantage of the new terminology is that it includes all types of vulvar SILs, it provides a solution to the concerns in relation to the application of LAST to vulvar lesion, and it is in accordance with the World Health Organization classification as well as the LAST, creating unity among clinicians and pathologists.

Epithelial vulvar neoplasms and their changing classification.

In recent years, there have been many changes in the classification scheme for squamous lesions of the vulva; this is primarily due to the assimilation of new scientific information into the diagnostic terminology. For example, over the past 75 years we have realized that precancerous and cancerous lesions of the vulva may be induced by a variety of preconditions, which are typically divided into human papillomavirus (HPV) and non-HPV precursor lesions. The latter include several dermatoses, especially lichen sclerosus and lichen planus. Additionally, we have learned that HPV on extramucosal and nongenital sites does not have the same malignant potential as on mucosal or genital sites. Because of the frequent changes in nomenclature due to these discoveries, both old and new terms continue to be used in clinical practice; a summary of these terms is provided to help prevent a misunderstanding of their scope and significance. Important points for clinicians and pathologists who are involved in the care of these patients are provided.

Vulvar inflammatory dermatoses: an update and review.

Currently, urogenital complaints are among the most common problems encountered by family practitioners, gynecologists, and dermatologists. In response to the intricacy of vulvar disorders, the International Society for the Study of Vulvovaginal Disease was created to facilitate the exchange between clinicians and pathologists involved in the care of these patients. Recent classifications for inflammatory disorders and intraepithelial neoplasm have been proposed. In addition, vulvar skin biopsies are the most common source of intradepartmental consultation during dermatopathology sign-out. The purpose of this article is to review the various inflammatory dermatoses of the vulva and to update readers with new advances regarding these entities.

Vulvar seborrheic keratosis: is there a relationship to human papillomavirus?

OBJECTIVE: We sought to determine the prevalence of human papillomavirus (HPV) subtypes in vulvar seborrheic keratoses (SK) by polymerase chain reaction (PCR) in women with a theoretically low risk of recent HPV transmission. We also attempted to identify which histopathologic features best correlated with HPV and specific subtypes. METHODS: Twenty-eight cases of vulvar SK in women older than 50 years old were retrospectively pulled from our files from a 7-year period. Cases were histologically examined for the presence of 7 features: parakeratosis, horn cysts, pigmentation, "clonal" cells, papillomatosis, "whorls," and reticulation of rete. For controls, PCR was performed on all cases for HPV detection and typing. Ten cutaneous SK and 7 vulvar condyloma acuminata were also evaluated for HPV by PCR. RESULTS: Twenty-one vulvar SK had sufficient genetic material for HPV PCR analysis. Only 3 (14.29%) were positive for HPV, 2 were type 6, and 1 was an unknown type. All cutaneous SK were negative and all condyloma acuminatum were positive for HPV. There was no histologic feature that separated HPV-positive from HPV-negative vulvar SK, although there was a tendency for parakeratosis to be associated with HPV positivity. CONCLUSIONS: The rate of HPV positivity in vulvar SK in women older than 50 years is much lower than expected and not statistically significantly associated with specific histologic features. One explanation may be that vulvar SK have diminishing levels of HPV genetic material in the relatively older ages of the patients in our study. Alternatively, vulvar SK may have no relationship to HPV, and strict histologic criteria may separate vulvar SK from condyloma acuminatum. In this instance, the few cases of HPV-positive vulvar SK may reflect incidental persistence of HPV in vulvar epidermis. Furthermore, these possibilities may vary among different populations, for example, based on patient age.

High-Yield Vulvar Histopathology for the Clinician.

Certain adjustable factors may influence how helpful a pathology report is to the clinician. Different biopsy techniques may be preferable based on the type of lesion being biopsied and the background epithelial surface. Key observations from the history and physical examination, possibly with a clinical photograph, are helpful to the pathologist. When reading the pathology report, realize the difficulties arising from definitively classifying some diseases and how treatment can affect the tissue. Finally, avoid miscommunication with the pathologist by understanding current nomenclature of vulvar disease.

The 2015 International Society for the Study of Vulvovaginal Disease (ISSVD) Terminology of Vulvar Squamous Intraepithelial Lesions.

OBJECTIVES: The impact of terminology for vulvar intraepithelial lesions has been significant over the years, because it has affected diagnosis, treatment, and research. The introduction of the Lower Anogenital Squamous Terminology (LAST) in 2012 raised 2 concerns in relation to vulvar lesions: firstly, the absence of reference to "differentiated vulvar intraepithelial neoplasia" (differentiated VIN) could lead to its being overlooked by health care providers, despite its malignant potential. Secondly, including the term "low-grade squamous intraepithelial lesion" (LSIL) in LAST recreated the potential for overdiagnosis and overtreatment for benign, self-limiting lesions. MATERIALS AND METHODS: The International Society for the Study of Vulvovaginal Disease (ISSVD) assigned the terminology committee the task of developing a terminology to take these issues into consideration. The committee reviewed the development of terminology for vulvar SILs with the previous 2 concerns in mind and reviewed several new terminology options. RESULTS: The final version accepted by the ISSVD contains the following: 1) Low-grade SIL of the vulva or vulvar LSIL, encompassing flat condyloma or human papillomavirus effect. 2) High-grade SIL or vulvar HSIL (which was termed "vulvar intraepithelial neoplasia usual type" in the 2004 ISSVD terminology). 3) Vulvar intraepithelial neoplasia, differentiated type. CONCLUSION: The advantage of the new terminology is that it includes all types of vulvar SILs, it provides a solution to the concerns in relation to the application of LAST to vulvar lesion, and it is in accordance with the World Health Organization classification as well as the LAST, creating unity among clinicians and pathologists.

Eruptive cherry hemangiomatosis associated with multicentric Castleman disease: a case report and diagnostic clue.

BACKGROUND: Eruptive cherry hemangiomatosis, which involves the sudden onset of multiple small vascular proliferations, has been rarely reported as a heralding sign of multicentric Castleman disease (MCD) and other lymphoproliferative diseases. We report a case wherein the rapid appearance of cherry hemangiomata is the presenting sign of MCD. OBSERVATIONS: A 25-year-old man with a 10-year history of benign vascular growths developed 23 cutaneous vascular proliferations and systemic symptoms 5 days prior to presentation. Biopsy of the cutaneous lesions revealed a polypoidal proliferation of vessels consistent with cherry hemangiomata. Laboratory studies disclosed systemic abnormalities, and the findings of a subsequent lymph node biopsy confirmed MCD. Combination chemotherapy was initiated, and the cutaneous proliferations improved in association with the systemic disease. CONCLUSIONS: There is a scarcity of literature describing the association between eruptive cherry hemangiomatosis and MCD. The likely underlying mechanism is hypersecretion of vascular endothelial growth factor secondary to an elevated interleukin 6 level. Failure to recognize this association may have led to diagnostic delays. The authors suggest careful evaluation and follow-up of all patients presenting with the sudden onset of cherry hemangiomata, particularly with systemic symptoms, lymphadenopathy, or other benign vascular endothelial growths, for the potential development of MCD and other lymphoproliferative diseases.

Eruptive post-chemotherapy in situ melanomas and dysplastic nevi.

A 22-year-old white man without a personal or family history of atypical nevi had received chemotherapy for pre-B-cell acute lymphocytic leukemia at age 17 that included L-asparaginase, prednisone, methotrexate, mercaptopurine, daunorubicin, and cytoxan. Two to three months after completing maintenance chemotherapy, the patient reports he developed many moles, which remained stable for approximately 2 years. Upon examination, two dark, atypical appearing plaques with irregular borders and numerous pink papules of varying shapes and sizes were noted on his chest, back, and abdomen. Histology of specimens of both types of lesions revealed three moderately atypical compound dysplastic melanocytic nevi and three in situ melanomas. The lesions with only features of dysplastic nevi exhibited dermal fibrosis, cytologic atypia, junctional shoulders, lentiginous spread, and focal pigmentation. The lesions with in situ melanomas in addition demonstrated pagetoid spread, extension down adnexal structures, and more severe cytologic atypia. Malignant melanoma has been associated with chronic immunosuppression, and benign nevi have been reported to erupt after chemotherapy. We report an occurrence of multiple eruptive dysplastic nevi and in situ melanomas appearing shortly after completion of chemotherapy.

Cutaneous clear-cell granular cell tumors: the histologic description of an unusual variant.

BACKGROUND: Granular cell tumors (GCTs) are neoplasms showing nerve sheath differentiation that can arise in the skin but, to our knowledge, have not been associated with significant clear-cell morphology. METHODS: Two patients developed four separate GCTs with distinctive, diffuse clear-cell change, which completely camouflaged the primary differentiation. The morphology, histochemistry and immunohistochemistry of the lesions are described and are compared with the presence and extent of clear-cell change in 14 other cases of GCTs. RESULTS: The index cases were relatively broad proliferations with uniform diffuse clear-cell change and only minimal overlying epidermal hyperplasia. Prominent lymphoid nodules were present at the periphery. These clear-cell granular tumors were positive for S-100 protein, p75, CD68, NKI/C3 and neuron-specific enolase and were negative for epithelial mucin, periodic acid-Schiff, carcinoembryonic antigen, HMB-45, Melan-A, smooth muscle actin, Leu7, synaptophysin, CD34, factor XIIIa, epithelial membrane antigen and cytokeratin. Three of the fourteen comparison cases were found to have no clear-cell change, eight showed focal clear-cell change and three showed moderate clear-cell change. CONCLUSIONS: The distinctive morphology and the immunohistochemical results are discussed in the context of the differential diagnosis of clear-cell cutaneous tumors.

Basal cell-signet-ring squamous cell carcinoma of the eyelid.

A 93-year-old woman developed a mass on her right lower eyelid that was present for more than 6 months but underwent rapid expansion during several weeks prior to her ophthalmological evaluation. Examination revealed an approximately 1.8 cm in diameter, fleshy, fungating growth involving more than 60% of the right lower eyelid. Excisional biopsy disclosed a neoplasm arising from the epidermis composed of adjoining basal cell and signet-ring squamous cell carcinoma, without a transition zone. The cells comprising the basal and squamous cell carcinomas were distinct immunophenotypically, with only the basal cell carcinoma reacting with Ber-EP4 and CAM 5.2 antibodies. To our knowledge, this case represents the first example of a collision tumor composed of basal cell and signet-ring squamous cell carcinoma.

Liver transplantation in Ellis-van Creveld syndrome: a case report.

This case represents a rare association of Ellis-van Creveld (EvC) syndrome, a chondroectodermal disorder, with congenital paucity of bile ducts. Sequential liver biopsies during the patient's childhood demonstrated progressive fibrosis that can occur in other chondrodysplastic malformations. However, this EvC case is the first report to demonstrate paucity of intra-hepatic bile ducts progressing to cirrhosis and subsequently requiring transplant.