Differentiated vulvar intraepithelial neoplasia (dVIN): the most helpful histological features and the utility of cytokeratins 13 and 17

Dasgupta, Shatavisha; Ewing‐Graham, Patricia C.; Kemenade, Folkert J. van; Doorn, Helena C. van; Hegt, Vincent Noordhoek; Koljenović, Senada

doi:10.1007/s00428-018-2436-8

Cited by 33 publications

(54 citation statements)

References 32 publications

(57 reference statements)

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“…Our data do not support notion that TP53 mutations are already present in the LS. As dVIN often resembles LS, and its histopathological diagnosis is challenging, the reported higher rates of TP53 mutations in LS might have been caused by the samples misdiagnosis caused by inadequate interpretation of morphological data as well as by the lack of unified guidelines for p53 expression assessment by immunohistochemistry [ 3 , 14 , 21 , 39 ]. However, the conclusions from our study are limited by the small LS sample number, and the same diagnostic challenges apply to our study.…”

Section: Discussionmentioning

confidence: 99%

Somatic Mutation Profiling in Premalignant Lesions of Vulvar Squamous Cell Carcinoma

Zięba

Pouwer

Kowalik

et al. 2020

IJMS

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Vulvar squamous cell carcinoma (VSCC) originates from the progression of either a high-grade squamous intraepithelial lesion (HSIL) or differentiated-type vulvar intraepithelial neoplasia (dVIN), often in a background of lichen sclerosus (LS). The mechanisms leading to the progression of these premalignant lesions to VSCC are elusive. This study aims to identify pathogenic mutations implicated in VSCC development. Using next-generation sequencing, 38 HSIL, 19 dVIN, 20 LS, of which 10 were solitary lesions and 10 with adjacent VSCC, and 10 VSCC adjacent to LS, were screened for hotspot mutations in 50 genes covered by the Ion AmpliSeq Cancer Hotspot Panel v2 Kit (Thermo Fisher Scientific). Pathogenic mutations of TP53 were the most common genetic alterations identified in 53% and 24% of dVIN and HSIL cases, respectively, followed by CDKN2A (p16) mutated in 42% and 0% of dVIN and HSIL, respectively. Seven (70%) and three (30%) of 10 cases of VSCC associated with LS carried TP53 and CDKN2A mutations, respectively, whereas neither solitary LS nor LS associated with VSCC cases harbored mutations in these genes. It appears that TP53 mutations are early events during VSCC carcinogenesis, being present in both HSIL and dVIN lesions. Our preliminary data do not support a genetic background for the notion of LS as the VSCC premalignant lesion.

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Section: Discussionmentioning

confidence: 99%

Somatic Mutation Profiling in Premalignant Lesions of Vulvar Squamous Cell Carcinoma

Zięba

Pouwer

Kowalik

et al. 2020

IJMS

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“…Clinical photographs of HPV-independent neoplasia often show concurrent lesions with diverse morphologies, and 20%–50% of women have 2 or more noncontiguous disease sites. 4 , 12 , 18 , 20 , 28 , 69 …”

Section: Methodsmentioning

confidence: 99%

Diagnostic Criteria for Differentiated Vulvar Intraepithelial Neoplasia and Vulvar Aberrant Maturation

Heller

Day

Allbritton

et al. 2020

J Low Genit Tract Dis

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Objective The aim of the study was to describe the features required for diagnosis of differentiated vulvar intraepithelial neoplasia (dVIN) and vulvar aberrant maturation (VAM). Materials and Methods The International Society of the Study of Vulvovaginal Diseases tasked the difficult pathologic diagnoses committee to develop consensus recommendations for clinicopathologic diagnosis of vulvar lichen planus, lichen sclerosus, and dVIN. The dVIN subgroup reviewed the literature and formulated diagnostic criteria that were reviewed by the committee and then approved by the International Society of the Study of Vulvovaginal Diseases membership. Results Differentiated vulvar intraepithelial neoplasia is the immediate precursor of human papillomavirus (HPV)–independent vulvar squamous cell carcinoma and shows a spectrum of clinical and microscopic appearances, some overlapping with HPV-related neoplasia. The histopathologic definition of dVIN is basal atypia combined with negative or nonblock-positive p16 and basal overexpressed, aberrant negative, or wild-type p53. The most common pattern of dVIN is keratinizing with acanthosis, aberrant rete ridge pattern, and premature maturation. The morphologic spectrum of keratinizing dVIN includes hypertrophic, atrophic, acantholytic, and subtle forms. A few dVIN cases are nonkeratinizing, with basaloid cells replacing more than 60% of epithelium. Vulvar aberrant maturation is an umbrella term for lesions with aberrant maturation that arise out of lichenoid dermatitis and lack the basal atypia required for dVIN. Conclusions Evaluation of women at risk for dVIN and VAM requires a collaborative approach by clinicians and pathologists experienced in vulvar disorders. Close surveillance of women with lichen sclerosus and use of these recommendations may assist in prevention of HPV-independent squamous cell carcinoma through detection and treatment of dVIN and VAM.

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“…Criteria for classic dysplasia adhere to the description of oral dysplasia of the WHO [2]. Differentiated dysplasia was scored by the criteria described in the vulva [11][12][13][14]. See the description in the introduction.…”

Section: Tissue Processing and Analysismentioning

confidence: 99%

“…Differentiated dysplasia is characterized by a basal layer of small cells with hyperchromatic or open nuclei with small nucleoli with an abrupt transition to suprabasal large cells with abundant, eosinophilic cytoplasm with differences in eosinophilia, intercellular edema with clearly visible desmosomes, and large, open nuclei with prominent nucleoli. The epithelium can be hyperplastic or flat [11][12][13][14]. In vulvar epithelium, usual dysplasia is associated with high-risk HPV infection, whereas differentiated dysplasia is not [14].…”

Section: Introductionmentioning

confidence: 99%

“…In vulvar epithelium, usual dysplasia is associated with high-risk HPV infection, whereas differentiated dysplasia is not [14]. Recent studies investigated the use of keratin 13 (CK13) and keratin 17 (CK17) as indicative markers associated with usual/classic and differentiated epithelial dysplasia, in that dysplastic lesions show a decreased expression of CK13 and an increased expression of CK17 [13,15,16]. Differentiated dysplasia is currently not acknowledged by the WHO as a separate morphological entity in the oral mucosa, and is therefore not considered in clinical decision management.…”

Section: Introductionmentioning

confidence: 99%

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Incorporation of differentiated dysplasia improves prediction of oral leukoplakia at increased risk of malignant progression

et al. 2020

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Oral leukoplakia is the most common oral potentially malignant disorder with a malignant transformation rate into oral squamous cell carcinoma of 1-3% annually. The presence and grade of World Health Organization defined dysplasia is an important histological marker to assess the risk for malignant transformation, but is not sufficiently accurate to personalize treatment and surveillance. Differentiated dysplasia, known from differentiated vulvar intraepithelial neoplasia, is hitherto not used in oral dysplasia grading. We hypothesized that assessing differentiated dysplasia besides World Health Organization defined (classic) dysplasia will improve risk assessment of malignant transformation of oral leukoplakia. We investigated a retrospective cohort consisting of 84 oral leukoplakia patients. Biopsies were assessed for dysplasia presence and grade, and the expression of keratins 13 (CK13) and 17, known to be dysregulated in dysplastic vulvar mucosa. In dysplastic oral lesions, differentiated dysplasia is as common as classic dysplasia. In 25 out of 84 (30%) patients, squamous cell carcinoma of the upper aerodigestive tract developed during follow-up. Considering only classic dysplasia, 11 out of 56 (20%) patients with nondysplastic lesions progressed. With the incorporation of differentiated dysplasia, only 2 out of 30 (7%) patients with nondysplastic lesions progressed. The risk of progression increased from 3.26 (Hazard ratio, p = 0.002) when only classic dysplasia is considered to 7.43 (Hazard ratio, p = 0.001) when classic and differentiated dysplasia are combined. Loss of CK13, combined with presence of dysplasia, is associated with greater risk of malignant progression (p = 0.006). This study demonstrates that differentiated dysplasia should be recognized as a separate type of dysplasia in the oral mucosa and that its distinction from classic dysplasia is of pathological and clinical significance since it is a strong (co) prognostic histopathological marker for oral malignant transformation. In oral lesions without dysplasia and retained CK13 staining the risk for progression is very low.

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Differentiated vulvar intraepithelial neoplasia (dVIN): the most helpful histological features and the utility of cytokeratins 13 and 17

Cited by 33 publications

References 32 publications

Somatic Mutation Profiling in Premalignant Lesions of Vulvar Squamous Cell Carcinoma

Somatic Mutation Profiling in Premalignant Lesions of Vulvar Squamous Cell Carcinoma

Diagnostic Criteria for Differentiated Vulvar Intraepithelial Neoplasia and Vulvar Aberrant Maturation

Incorporation of differentiated dysplasia improves prediction of oral leukoplakia at increased risk of malignant progression

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