RESUMEN
BACKGROUND: Digital droplet PCR (ddPCR) is a relatively new technique used to detect molecular alterations with unprecedented precision and accuracy. It is particularly useful for detecting point mutations and copy number variation (CNV) in samples with small amounts of target DNA. This proof of principle study was conducted to see if ddPCR technology could be applied to cytology specimens to detect molecular alterations which may influence diagnostic decision making. METHODS: A range of cytological specimens derived from bladder or pancreaticobiliary origin, with varying diagnoses but with an emphasis on abnormality, underwent ddPCR testing. DNA was manually extracted from Thinprep vials, cell blocks or direct fine needle aspiration smears. ddPCR was performed using two somatic point mutations TP53 R248W and TP53 R273H assays for both urine and pancreaticobiliary cytology specimens. Three CNV assays; CDKN2A, E2F3 and YWHAZ were applied to urine samples. SMAD4 and CDKN2A CNVs were applied to the pancreaticobiliary samples. RESULTS: 16 of 21 urine specimens showed molecular alterations using ddPCR testing. 12 of those 16 cases were associated with malignant outcomes. The pancreaticobiliary specimens showed 14 of 37 specimens with molecular alterations, all of which were associated with carcinoma. We demonstrated an increasing percentage of molecular aberrations associated with increasing severity of cytological results. CONCLUSION: Our results have shown that ddPCR can identify both mutations and CNVs in urine and pancreaticobiliary cytology derived samples. Being able to detect these molecular alterations may reduce the number of equivocal results leading to more timely and informed patient management decisions.
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Carcinoma , Vejiga Urinaria , Humanos , Variaciones en el Número de Copia de ADN/genética , Reacción en Cadena de la Polimerasa/métodos , MutaciónRESUMEN
OBJECTIVES: Three types of lichen planus (LP) occur on the vulva: erosive, classic, and hypertrophic. The latter 2 occur on keratinized skin and little is known about their clinicopathologic appearance. MATERIALS AND METHODS: Vulvar biopsies of keratinized skin reported as LP or "lichenoid" between 2011 and 2017 were reviewed. Inclusion required age of older than 18 years, a lichenoid tissue reaction, and insufficient abnormal dermal collagen to diagnose lichen sclerosus. Clinical and histopathologic data were collected and cases were categorized as hypertrophic, classic, or nonspecific lichenoid dermatosis. Descriptive statistics were performed and groups were compared with the Fisher exact test. RESULTS: Sixty-three cases met criteria for inclusion. Twenty-nine (46%) cases were categorized as hypertrophic LP, 21 (33%) as classic LP, and 13 (21%) as nonspecific lichenoid dermatosis. There were no significant differences in age, primary symptom, biopsy location, or duration of disease between the 3 groups. When compared with classic and nonspecific disease, hypertrophic LP was less likely to have comorbid dermatoses and more likely to be red, diffuse, have scale crust, and contain plasma cells in the infiltrate. Nonspecific disease had similar clinical features to classic LP but was less likely than the other 2 categories to have a dense lymphocytic infiltrate and exocytosis. CONCLUSIONS: Vulvar LP on keratinized skin has a diversity of appearances and presents a clinicopathologic challenge. Further research is required to understand the natural history of hypertrophic LP and the underlying diagnosis of nonspecific lichenoid cases.
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Liquen Plano/patología , Enfermedades de la Vulva/patología , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Femenino , Histocitoquímica , Humanos , Liquen Plano/clasificación , Microscopía , Persona de Mediana Edad , Estudios Retrospectivos , Enfermedades de la Vulva/clasificación , Adulto JovenRESUMEN
OBJECTIVE: The aim of the study was to assess for the presence of vulvar lichen planus (LP) in association with human papillomavirus (HPV)-independent squamous cell carcinoma (SCC). MATERIALS AND METHODS: We performed a clinicohistopathologic review of consecutive vulvectomies and wide local excisions for HPV-independent vulvar or vaginal SCC from 2007 to 2017. Data collected included site of SCC, adjacent precursor lesions and dermatoses, dermatologic treatment, and outcome. RESULTS: There were 43 cases of primary HPV-independent vulvar SCC treated by excision, but no vaginal cancers. Eighteen women (42%) had a preoperative diagnosis of lichen sclerosus (LS); none had a diagnosis of LP. Topical corticosteroids were prescribed in 19 (44%) of 43, with 4 women placed on maintenance therapy. Tumors arose from the labia minora, labia majora, and periclitoris, but not from vestibule or perianus. On histopathological review, LS was present in 41 (95%) of 43 specimens, 1 had a nonspecific lichenoid reaction, and 1 had lichen simplex; both of the latter had subsequent biopsies showing LS. Lichen planus was not seen in association with SCC. Differentiated vulvar intraepithelial neoplasia (dVIN) was present in 38 (88%) of 43 specimens, whereas 1 had acanthosis with altered differentiation and 4 (9%) had no precursor lesion. Differentiated vulvar intraepithelial neoplasia had standard, basaloid, and hypertrophic morphology, superficially resembling erosive LP in 9 (24%) of 38 and hypertrophic LP in 6 (16%) of 38. CONCLUSIONS: Lichen planus was not seen in association with HPV-independent vulvar SCC, whereas LS was underrecognized and inadequately treated in this group. Pathologists should be aware that dVIN may superficially resemble erosive or hypertrophic LP.
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Carcinoma de Células Escamosas/diagnóstico , Liquen Escleroso y Atrófico/diagnóstico , Displasia del Cuello del Útero/patología , Vulva/patología , Corticoesteroides/uso terapéutico , Adulto , Anciano , Carcinoma de Células Escamosas/complicaciones , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/cirugía , Bases de Datos Factuales , Femenino , Humanos , Liquen Plano/complicaciones , Liquen Plano/tratamiento farmacológico , Liquen Escleroso y Atrófico/tratamiento farmacológico , Liquen Escleroso y Atrófico/epidemiología , Persona de Mediana Edad , Nueva Gales del Sur/epidemiología , Papillomaviridae , Displasia del Cuello del Útero/complicaciones , Displasia del Cuello del Útero/cirugía , Vulva/microbiologíaRESUMEN
OBJECTIVE: The aim of the study was to assess clinical and histopathologic characteristics of symptomatic women who underwent a nondiagnostic biopsy of the inner vulva. MATERIALS AND METHODS: Consecutive nondiagnostic biopsies from medial labia minora, posterior fourchette, and vestibule obtained from symptomatic women between 2011 and 2015 were reviewed for this retrospective histopathologic case series. Histopathologic assessment included site, basal layer appearance, lymphocytic infiltrate, and presence of fibrosis or sclerosis. Examination findings, treatment, initial impression, and final clinical diagnosis were recorded. Descriptive statistics were performed; clinical and histopathologic characteristics were compared with Fisher exact test. RESULTS: There were 85 cases; mean age was 53 years. Most women presented with painful erythema and underwent biopsy to confirm (30, 35%) or exclude (43, 51%) lichen planus. After clinical follow-up and histopathologic review, most cases had persistent diagnostic discordance. Final clinical diagnoses were available in 70 women: lichen planus in 27 (38%), vulvodynia in 15 (21%), and the other 28 (40%) had LS (8), plasma cell vulvitis (5), psoriasis (4), dermatitis (4), candidosis (3), estrogen deficiency (3), and aphthosis (1). Histopathologic review highlighted the difficulty in distinguishing mucosa-associated lymphoid tissue from an inflammatory infiltrate in 23 (27%) of cases. Compared with other sites, biopsies from the mucocutaneous junction were more likely to be associated with a positive culture for Candida albicans. CONCLUSIONS: Nondiagnostic biopsies from the inner vulva should prompt thoughtful multidisciplinary review, but more research is required to resolve the problem of clinicopathologic discordance through better understanding of vulvar histology and pathophysiology.
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Biopsia , Histocitoquímica/métodos , Enfermedades de la Vulva/diagnóstico , Enfermedades de la Vulva/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVES: To identify features that could define papillary ductal cell proliferation within the C3 category and to subcategorise papillary lesions into benign papillomas which can be managed conservatively and atypical/malignant papillary neoplasms which require surgical intervention. STUDY DESIGN: A blind microscopic rescreen of all C3 cases was conducted. The corresponding histological outcome was compared with the cytology. Statistical analysis was performed using papillary versus non-papillary outcomes and benign versus atypical/malignant papillary lesions. In addition, macropapillary lesions (papilloma and encysted papillary carcinoma) were plotted against micropapillary ductal carcinoma in situ. RESULTS: Two hundred thirty FNA cases reported as C3 included 72 papillary neoplasms (52 benign papillomas and 20 atypical/malignant papillary lesions). Features specific to papillary lesions within C3 include macropapillary fragments, complex sheets, palisading strips, cystic background, cohesion and a decreased nuclear-to-cytoplasmic ratio. Features favouring atypical/malignant papillary lesions include decreased numbers of bare bipolar nuclei, discohesion and a non-cystic background. These features are common to most breast malignancies; however, identification of papillary features often results in a downgraded diagnosis from C5. CONCLUSIONS: This study supports the ability to reliably identify papillary ductal cell proliferation within C3. Certain features can distinguish papillary lesions from other C3 pathologies. This separation is likely to be clinically useful as papillary lesions may require a different management approach.
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Neoplasias de la Mama/patología , Mama/patología , Carcinoma Papilar/patología , Proliferación Celular/fisiología , Diagnóstico Diferencial , Femenino , Humanos , Persona de Mediana Edad , Papiloma/patologíaRESUMEN
BACKGROUND: Fine-needle aspiration (FNA) of difficult breast lesions often results in an atypical (C3) report. The assortment of outcomes generated by C3 reports varies widely, and this has given rise to different clinical management pathways. OBJECTIVE: To identify and objectively assess microscopic features associated with atypical/C3 breast FNA cases. MATERIALS AND METHODS: A total of 230 atypical breast FNAs were subjected to a blind microscopic rescreen using a range of robust qualitative and quantitative cytological criteria including cellularity, architectural qualities, cytomorphology and background features. A logistic regression with a receiver operating characteristic (ROC) curve and the resultant forward stepwise analysis were conducted to assess the results. This statistical testing was measured against malignant, benign proliferative and benign non-proliferative outcomes. RESULTS: The malignant and benign proliferative outcomes showed a mixture of opposing protective and predictive individual cytological criteria. The stepwise analysis produced models demonstrating the best combination of individual cytological criteria for malignancy, proliferative and benign non-proliferative entities. In the malignancy model, discohesion, nuclear crowding within sheets, diminished numbers of bare bipolar nuclei and myoepithelial cells, the presence of tubules or necrosis and the absence of a cystic background were important features. The benign proliferative model suggested the same criteria but with the opposite implication and with the addition of several others, such as the presence of apocrine metaplasia, retained polarity and a speckled or coarse chromatin pattern. Age was a significant factor in malignant and proliferative outcomes. The benign non-proliferative stepwise analysis produced a model with fewer criteria (complex sheets, bare bipolar nuclei and a cystic background) limiting clinical application. CONCLUSION: Atypical/C3 breast cytology remains a legitimate reporting category. However, it is associated with a number of different histological outcomes. The incidence of the C3 category can be significantly reduced by controlling extrinsic factors and understanding the associated microscopic features.