Sinonasal Papillomas and Carcinomas: A Contemporary Update With Review of an Emerging Molecular Classification.

CONTEXT.­: Sinonasal papillomas and carcinomas are uncommon head and neck neoplasms that comprise a broad clinicopathologic and morphologic spectrum, and thus frequently represent a diagnostic challenge for surgical pathologists. Recent molecular interrogation of these tumors has delineated a number of recurrent alterations that correspond to distinct entities with potential diagnostic and/or therapeutic clinical utility. OBJECTIVE.­: To summarize the salient clinicopathologic, morphologic, and molecular features of sinonasal papillomas and carcinomas. DATA SOURCES.­: Review of pertinent literature regarding sinonasal papillomas and sinonasal carcinomas. CONCLUSIONS.­: Despite their relative rarity in many surgical pathology practices, sinonasal papillomas and carcinomas frequently demonstrate characteristic morphologic features that are important for accurate diagnosis. Given our emerging understanding of the molecular basis for these tumors, judicious use of available ancillary tools-including immunohistochemistry and in situ hybridization-may be helpful in subsets of cases, whereas additional molecular testing may be useful for diagnostically challenging and/or clinically aggressive sinonasal tumors.

Management of BIRADS 3, 4A, and 4B Lesions Diagnosed as Pure Papilloma by Ultrasound-Guided Core Needle Biopsy: Is Surgical Excision Necessary?

RATIONALE AND OBJECTIVES: There is lack of consensus on managing papillomas due to varied upgrade rates in the literature related to variability in the studied populations. We specifically studied upgrade rates of pure papilloma diagnosed with ultrasound core biopsy (UCB) using spring-loaded (SLB) and vacuum-assisted (VAB) biopsy devices in patients with low-to-intermediate pre-test probability for malignancy on imaging. MATERIALS & METHODS: From 01/01/2008 to 06/30/2016, 227 patients with 248 pure papillomas classified as BI-RADS 3, 4a, and 4b were diagnosed by UCB and underwent surgical excision or clinical and/or imaging follow-up. Imaging features, biopsy device, and final pathology were documented. RESULTS: 177 lesions were biopsied with SLB (14-gauge) and 71 lesions with VAB (9-13 gauges). At surgery, upgrade rates to high-risk lesions and malignancy for SLB were 14.3% (22/154) and 1.9% (3/154), and for VAB were 3.5% (2/57) and 0% (0/57), respectively (p < 0.05). The combined surgical upgrade rate to high-risk lesions and malignancy was 11.4% (24/211) and 1.4% (3/211), respectively. The overall upgrade rate (including surgical and clinical and/or imaging follow-up) to high-risk lesions and malignancy was 9.7% (24/248) and 1.2% (3/248), respectively. No ultrasound features were predictive of upgrade. Rates of complete excision were 7.1% (11/154) for SLB and 19.3% (11/57) for VAB (p < 0.05). CONCLUSION: BI-RADS 3, 4a, or 4b masses biopsied with UCB revealed pure papilloma upgrade to malignancy in less than 2% of cases. SLB was associated with greater upgrades compared with VAB. Therefore, follow-up imaging is a reasonable alternative to excision, particular in those sampled by VAB. Excision could be considered if the diagnosis of a high-risk lesion would change clinical management.

New insights into naevoid melanomas: a clinicopathological reassessment.

AIMS: Because the term 'naevoid melanoma' has variable clinical and pathological interpretations, we aimed to clarify the features of melanomas referred to as naevoid. METHODS AND RESULTS: A review was undertaken of 102 melanomas diagnosed histopathologically as naevoid melanomas and ascertained by European Organization for Research and Treatment of Cancer Melanoma Group Subcommittee pathologists from their records. We found these could be classified morphologically into three groups. Thirteen melanomas were overlying genuine naevi and were therefore excluded. Of the 89 melanomas considered to be naevoid, 11 presented clinically as exophytic papillomatous nodules with little junctional component and composed of small atypical cells showing numerous mitoses and no change with depth; we termed these 'papillomatous naevoid' melanomas. The other 78 were flat or only slightly raised, and had a superficial spreading melanoma-like component with maturation to a small cell, but still an atypical, dermal component; we termed these 'maturing naevoid' melanomas. We showed that papillomatous and maturing naevoid melanomas also have differing immunochemical profiles. Preliminary clinical follow-up suggested different outcomes for these two naevoid melanoma types. CONCLUSIONS: Melanomas that have been classified as naevoid melanomas comprise two types with distinct clinical, histopathological and immunohistochemical features that may also be prognostically significant.

Analysis of HSP90 Expression Is Valuable in the Differential Diagnosis of Ocular Surface Squamous Lesions.

OBJECTIVES: The aim of this study was to evaluate heat shock protein 90 (HSP90) expression in squamous lesions (SLs) and to assess its diagnostic value for different lesions within the SL spectrum. METHODS: A total of 70 conjunctival SLs, including 19 papillomas, 22 cases of conjunctival intraepithelial neoplasia (ConINs) I, 11 cases of ConIN II, six cases of ConIN III, and 12 squamous carcinomas (sqCAs), were evaluated using the German immunoreactive score against HSP90. RESULTS: Cytoplasmic HSP90 expression differed between low- and high-grade lesions (P < .001). Among high-grade lesions, the nuclear HSP90 score was higher in the ConIN III-sqCA group than in the ConIN II group (P = .0162). A percentage of total thickness staining of less than 73% differentiated between ConIN III and sqCA. CONCLUSIONS: The expression of HSP90 is particularly useful to differentiate low-grade from high-grade lesions of the conjunctiva. HSP90 may play an important role in the malignant transformation of SLs and could be a new target for therapy.

The predictive ability of a CK5/p63/CK8/18 antibody cocktail in stratifying breast papillary lesions on needle biopsy: an algorithmic approach works best.

OBJECTIVES: Immunohistochemical markers have been shown to assist in the stratification of breast papillary lesions. We evaluated the ability of different cytokeratin (CK) and p63 expression profiles on needle biopsy specimens to predict excision diagnoses. METHODS: A CK5/p63/CK8/18 antibody cocktail was applied to 58 needle biopsy specimens (32 papillomas, 7 atypical papillomas, 19 papillary carcinomas on excision). RESULTS: p63 expression was greater in papillomas than in atypical papillomas (P = .044) and papillary carcinomas (P< .0001). Papillary carcinomas and atypical papillomas showed greater CK8/18 expression (and conversely less CK5 expression) than did papillomas (P < .0001). Negative or focal p63 expression was 96% sensitive for diagnosing any atypical lesion (atypical papilloma or papillary carcinoma) on excision, whereas CK8/18 predominant expression (≥80% cells) was 100% sensitive. In contrast, the sensitivity of the original diagnosis was only 81%. The greatest accuracy for the diagnosis of atypical papillary lesions (95%) was achieved when both p63 and cytokeratins were used in combination in an algorithmic fashion. This method also correctly identified all cases that had papillary carcinoma (100% sensitivity) on excision. CONCLUSIONS: Although a single stain or combination cannot independently stratify papillary lesions, a CK5/p63/CK8/18 antibody cocktail is a useful adjunct to morphology for evaluating breast papillary lesions in needle biopsy specimens.

Schneiderian papillomas: comparative review of exophytic, oncocytic, and inverted types.

BACKGROUND: Sinonasal papillomas are benign epithelial neoplasms arising from Schneiderian mucosa. The three subtypes, exophytic, oncocytic, and inverted (inverted papilloma [IP]), should be distinguished from one another histopathologically. This study (1) highlights the histopathological and clinical differences between the Schneiderian papilloma subtypes and (2) identifies clinical features that potentially predict papilloma subtypes. METHODS: A retrospective review was performed of patients with Schneiderian papillomas over an 11-year period. RESULTS: Seventy patients with sinonasal papillomas who underwent sinus surgery were identified. There were 50 (71%) male and 20 (29%) female subjects diagnosed at an average age of 53 years (range, 13-80 years). Exophytic (n = 25), oncocytic (n = 9), and IP (n = 37) were identified. IP was associated with transformation into squamous cell carcinoma in three (8%) cases and dysplasia in three (8%) cases. Neither oncocytic nor exophytic subtypes were associated with dysplasia or malignancy. On multivariate analysis of potential predictors of papilloma subtype, history of chronic rhinosinusitis (CRS) and location of papilloma were significantly associated with papilloma subtype. Using classification and regression tree model, papilloma subtypes can be predicted based on presence or absence of CRS and papilloma location with nominal 82.4% accuracy. CONCLUSION: The inverted and exophytic type are the most common sinonasal papillomas, with the inverted type having an 8% rate of malignant transformation in this study. In contrast, the oncocytic type was not associated with dysplasia or malignancy in our series despite reports in the literature indicating malignant potential. History of CRS and papilloma location can provide clues to the histological subtype, which is important for surgical planning and patient counseling.

Typical and unusual sonoelastographic patterns of breast cystic lesions: impact on BI-RADS classification.

PURPOSE: To describe the sonoelastographic appearance of breast cysts (simple, complicated-cysts with sedimentation and complex-cysts with internal solid parts). To assess the influence of sonoelastography on the BI-RADS classification of complicated cysts. MATERIALS AND METHODS: A prospective study was conducted and all cysts diagnosed by the same radiologist between May 2007 and July 2008 in our breast unit were included. Each lesion was assessed according to BI-RADS and the Tsukuba elasticity score using a Hitachi 8500 US device. Cytology or histopathology was obtained for complicated and complex cysts. RESULTS: 49 simple, 43 complicated and 14 complex cysts were detected. The elasticity patterns were divided into 4 categories: typical BGR (blue-green-red) pattern, appearance similar to that described for solid. lesions, variants of BGR, an inverse score of 3. The BGR pattern was predominant in breast cysts. Atypical elasticity patterns were mostly associated with complicated and complex cysts. BI-RADS classification of complicated cysts before and after elastography showed a statistically significant difference in terms of final category assessment (most of the complicated cysts were downgraded to BI-RADS 2 after elastography). CONCLUSION: Being aware of the wide spectrum of elastographic patterns of breast cysts and considering elastography when assessing the BI-RADS category of complicated cysts may lead radiologists to better patient management.

Papillary neoplasms of the breast: a review.

CONTEXT: Interpretation of papillary lesions of the breast remains a challenging task because of the wide morphologic spectrum encountered in the benign, atypical, and malignant subtypes. Data on clinical significance and outcome of papillary lesions, with superimposed atypia or areas similar to ductal carcinoma in situ partially replacing the benign elements, are sparse. Furthermore, complete excision of even a fully developed papillary carcinoma confined to a dilated or cystic duct is associated with an excellent prognosis, whereas a complex papilloma extending into multiple branches of a duct may ultimately recur as a carcinoma because of incomplete excision of microscopic foci. This makes an outcome-based classification difficult. OBJECTIVE: An arbitrary yet practical approach to classification is outlined, with discussion of methods to circumvent the various diagnostic difficulties. The limitations in precise diagnosis of papillary lesions in aspirates are addressed, and the implications of finding papillary lesions in core biopsies are discussed. Although the focus is on intraductal lesions, associated invasive carcinomas and invasive micropapillary carcinoma are also presented. DATA SOURCES: The literature on papillary lesions and invasive micropapillary carcinoma is reviewed. CONCLUSIONS: It would be prudent to completely excise any papillary lesion that has not been entirely removed by the initial core biopsy. The optimal management of localized papillary lesions is complete excision with a small rim of uninvolved breast tissue without any prior needle instrumentation if and when the papillary nature can be determined by imaging. Thus managed, most of these lesions behave indolently, and outcome is usually excellent.

[WHO classification of tumours of the CNS: revised edition of 2007 with critical comments on the typing und grading of common-type diffuse gliomas]. / WHO-Klassifikation der ZNS-Tumoren: Revidierte Fassung von 2007 mit kritischen Anmerkungen zum "Typing" und "Grading" diffuser Gliome.

The fourth edition of the WHO classification of tumours of the CNS was published in 2007. Six new entities were codified: angiocentric glioma (AG); papillary glioneuronal tumour (PGNT); rosette-forming glioneuronal tumour of the fourth ventricle (RGNT); papillary tumour of the pineal region (PTPR); spindle cell oncocytoma of the adenohypophysis (SCO); and pituicytoma. Furthermore, six histological variants of well-known brain tumours have been added, partially because they show different biological behaviour and/or prognosis: pilomyxoid astrocytoma; atypical choroid plexus papilloma; medulloblastoma with extensive nodularity; anaplastic medulloblastoma; extraventricular neurocytoma; non-specific variant of dysembryoplastic neuroepithelial tumour (DNT). The new entities and variants are discussed in this review. Moreover, the typing und grading of common-type diffuse gliomas, as well as the WHO grading system, are critically reviewed, particularly with regard to the prognostically important differential diagnosis of diffuse astrocytomas und oligodendrogliomas.

Características clínicas e histopatológicas da placa aural em eqüinos das raças Mangalarga e Quarto de Milha / Clinical and histopathological characteristics of the aural plaque in Mangalarga and Quarter Horses

Placa aural é uma variante da papilomatose eqüina. Foram examinados 306 eqüinos da raça Mangalarga e 275 da raça Quarto de Milha, com o objetivo de comparar a ocorrência da placa aural entre os animais destas raças, e caracterizar os achados clínicos e histopatológicos desta enfermidade. A ocorrência da placa aural foi 57 por cento nos eqüinos da raça Mangalarga e 35 por cento nos eqüinos da raça Quarto de Milha. Clinicamente as lesões consistiram de placas aplainadas, descamativas e hipocrômicas, formadas com freqüência pela coalescência de pequenas pápulas. Os principais achados histopatológicos foram hiperplasia epidérmica e hipomelanose levando à alteração abrupta entre o epitélio normal e o epitélio acometido pela placa aural.

Aural plaque is a variant of equine papillomatosis. Clinical examination was performed on 306 Mangalarga and 275 Quarter Horses to compare the occurrence of aural plaques among animals and to characterize clinical and histological findings for the disease. Aural plaques occurred in 57 percent of Mangalarga and in 35 percent of Quarter breeds. Clinically the lesions consisted of flat, desquamated and hypochromic plaques formed by coalescence of small papules. The main histopathological findings were epidermal hyperplasia and hypomelanosis with abrupt change between the normal and the affected epithelium.

Morphological diagnosis of urothelial neoplasms.

The morphological classification and diagnosis of bladder neoplasms is summarised, with specific focus on histological typing, grading and staging. Four diagnostic categories are described on the basis of the pattern of growth of the urothelial lesions and tumours (flat, exophytic or papillary, endophytic, and invasive). The WHO 2004 classification is currently used. However, the WHO 1973 classification is still considered by many urologists and oncologists as the international standard in patient management.

Papillary tumor of the pineal region and spindle cell oncocytoma of the pituitary: new tumor entities in the 2007 WHO Classification.

We have reviewed the features of two recently described intracranial tumors, which have been formally recognized as distinct entities by the 2007 WHO Classification of Brain Tumours: Papillary tumor of the pineal region and spindle cell oncocytoma of the pituitary gland. Their salient clinicopathological features, differential diagnosis, histogenetic hypothesis and outcome are discussed.

Severity of juvenile onset recurrent respiratory papillomatosis is not associated with socioeconomic status in a setting of universal health care.

BACKGROUND: Juvenile onset recurrent respiratory papillomatosis (JORRP) results from HPV transmission. Cervical cancer, also transmitted via HPV, is known to be correlated with socioeconomic status (SES). This study aims to determine if an association exists between SES and severity of JORRP. METHODS: Cross-sectional study of all active JORRP patients at the Hospital for Sick Children in Toronto in 2005. SES information from Hollingshead surveys, Postal walk Census data, and Low Income Cutoff Data were compared with Derkay-Wiatrak disease severity scores, peak annual surgical frequency, and age of diagnosis. Statistical analysis was performed using Spearman, Mann-Whitney, and linear regression analyses. RESULTS: Twenty-one patients were surveyed. Hollingshead results were as follows: two patients (10%) were class I (major business and professional); 11 patients (52%) were class II (medium business, minor professional, technical); 4 patients (19%) were class III (skilled craftsmen, clerical, sales workers); 4 patients (19%) were class IV (machine operators, semiskilled workers); 0% were from class V (unskilled laborers, menial service workers). Interestingly, based on postal code data nine patients (45%) were below the low income cutoff as compared to the Toronto (metropolitan) and Ontario (provincial) rates of low income (17% and 14%, respectively). There was significant correlation between each of the SES measures and between disease severity measures. However, analysis of the SES measures versus disease severity measures did not demonstrate any significant relationship. CONCLUSIONS: Though almost half the patients lived below the low income cutoff, this study did not demonstrate a significant correlation between socioeconomic status and severity of disease in JORRP. One possible explanation is that universal access to the Canadian health care system is able to provide support despite a large proportion of patients being socioeconomically vulnerable. A national level study is underway to further detect any relationship between SES and JORRP severity in the general population.

Virus del papiloma humano y adolescencia / Human papillomavirus and adolescence

No disponible

Displasia y carcinoma en papilomas schneiderianos nasosinusales. Estudio de 4 casos / Dysplasia and carcinoma in sinonasal schneiderian papillomas. A study of 4 cases

Se revisa en este trabajo la existencia de displasia y/ocarcinoma en una serie de 65 papilomas schneiderianosnasosinusales diagnosticados en nuestro centro en un periodode 17 años. Los papilomas se tipifican como fungiformes,invertidos, y oncocíticos de células cilíndricas,siguiendo las clasificaciones al uso. Se demuestran cambiosdisplásicos y/o carcinoma en 4 casos, todos ellos varones.En éstos, se estudian las características clínicas, incluyendoel seguimiento posterior al tratamiento, e histológicas. Porúltimo, se revisa la literatura existente sobre la asociaciónde papilomas nasosinusales con cambios neoplásicos o preneoplásicosen su epitelio

The presence of dysplasia and/or carcinoma in a seriesof 65 sinonasal schneiderian papillomas diagnosed in ourInstitution along a 17 year period is reviewed. The caseshave been typified as fungiform, inverted, and oncocyticwith cylindrical cells following current classifications.Dysplastic changes and/or carcinoma were demonstrated in4 cases, all of them male patients. Clinical data, includingpostreatment follow up and histological features of the caseswere analysed. Also, the literature concerning schneiderianpapillomas associated with dysplasia or carcinoma wasreviewed

Urothelial papilloma of the bladder: a review of 34 de novo cases.

BACKGROUND: Urothelial papilloma of the bladder is an uncommon entity when using restrictive diagnostic criteria. DESIGN: We retrospectively studied 34 patients who were diagnosed with urothelial papilloma of the bladder using the criteria of the 1998 WHO/ISUP classification system. Six cases were in-house and the remaining 28 were referred from other institutions as consults to one of the authors. In all cases, the diagnosis of papilloma was the first manifestation of urothelial neoplasia. RESULTS: The mean age of the patients at diagnosis was 57.8 years (range, 23-87 years). The male-to-female ratio was 2.4:1 (24 males and 10 females). The tumor size averaged 3.3 mm (range, 1-20 mm; median, 2 mm). Simple papillary fronds were seen in all cases; in 5 cases the additional finding of secondary budding off of small fronds from larger ones was also seen. In all cases, the fronds had a round morphology; yet in 4 cases elongated fronds were also noted. In 5 cases, dilated lymphatics within the fibrovascular fronds were apparent. One case had foamy histiocytes within the fibrovascular stalks. In all cases, the lining consisted of normal-appearing urothelium without hyperplasia, dysplasia, and/or mitotic figures. Some of the distinctive histologic features seen were changes in the umbrella cells: vacuolization (n = 4), prominence with cytologic atypia (n = 2), eosinophilic syncytial morphology (n = 1), apocrine-like morphology (n = 1), and mucinous metaplasia (n = 1). Follow-up was available in 26 cases with a mean follow-up for those without evidence of progression of 28.9 months (range, 3-127 months). Three patients (8.8%) developed recurrent papilloma 4, 15, and 18 months after the initial diagnosis of papilloma; 1 of these patients also showed progression to noninvasive low-grade urothelial carcinoma at the time of recurrence (15 months). Three patients (8.8%) progressed to higher-grade disease: 2 to noninvasive low grade urothelial carcinoma (11 and 15 months after the original diagnosis) and 1 to a papillary urothelial neoplasm of low malignant potential at 104 months and a noninvasive low-grade urothelial carcinoma at 141 months from the initial diagnosis of papilloma. None of the patients demonstrated progression to either lamina propria (T1) or muscularis propria (T2) invasion. Two patients died of unrelated causes. None of the patients died of bladder cancer. CONCLUSION: Patients with urothelial papillomas have a low incidence of recurrence and rarely progress to develop urothelial carcinoma. It seems reasonable to avoid labeling these patients as having cancer. It remains to be studied whether and when patients with papillomas who have no evidence of recurrence or progression no longer need to be followed.

Noninvasive papillary proliferations.

The diagnosis of noninvasive papillary tumors begins with categorization of the lesions as macropapillary or micropapillary. Macropapillary lesions include papilloma, papillary carcinoma, and papilloma harboring carcinoma. Papillomas consist of a few broad fronds, abundant stroma, and an epithelium containing both luminal and myoepithelial cells. Papillary carcinomas have many irregular fronds, small amounts of stroma, and a uniform population of malignant glandular cells. Papillomas can give rise to both conventional ductal hyperplasia and carcinomas. One analyzes proliferations on the surface of a papilloma as one would analyze those in a duct. Proliferations within the stalk of a papilloma require especially careful attention; one must observe large masses of cells demonstrating both cytological and architectural atypicality and devoid of intervening stroma to make the diagnosis of low-grade ductal carcinoma in-situ involving the stalk of a papilloma. Micropapillary proliferations represent either ductal hyperplasia or ductal carcinoma in situ. The former shows slight dilatation of ducts, micropapillae of similar size and shape, maturation of cells, lack of dishesion and necrosis, and lack of cytological atypicality. Micropapillary ductal carcinoma in situ exhibits extreme dilatation of ducts and lobules, micropapillae varying in size and shape, lack of maturation, dishesion and necrosis, and cytological atypicality.