Intraductal carcinoma of the prostate in the absence of high-grade invasive carcinoma represents a molecularly distinct type of in situ carcinoma enriched with oncogenic driver mutations.

Intraductal carcinoma of the prostate (IDC-P) most often appears associated with high-grade invasive prostate carcinoma (PCa), where it is believed to represent retrograde spread. However, IDC-P rarely occurs as an isolated finding at radical prostatectomy or with concurrent low-grade (Grade Group 1) invasive carcinoma. We hypothesized that isolated IDC-P (iIDC-P) in these unusual cases may represent a distinct in situ lesion and molecularly profiled 15 cases. iIDC-P was characterized by copy number alteration (CNA) profiling and targeted next generation sequencing in cases with sufficient tissue (n = 7). Immunohistochemistry for PTEN and ERG was performed on the total cohort (n = 15), where areas of iIDC-P and associated invasive disease were evaluated separately (n = 9). By copy number profiling, iIDC-P alterations were similar to those previously described in high-grade invasive PCa (PTEN, RB1, and CHD1 loss; MYC gain). However, in four cases, targeted sequencing revealed a striking number of activating oncogenic driver mutations in MAPK and PI3K pathway genes, which are extraordinarily rare in conventional PCa. In addition, pathogenic mutations in DNA repair genes were found in two cases of iIDC-P (BRCA2, CHEK2, CDK12) and other known PCa-associated mutations (FOXA1, SPOP) in two cases. Overall, ERG was expressed in 7% (1/15) of the iIDC-P lesions and PTEN was lost in 53% (8/15). Discordance for ERG or PTEN status between IDC-P and the low-grade PCa was observed in five of nine cases, with intact PTEN in the invasive tumor and PTEN loss in IDC-P in four. Despite a CNA profile similar to conventional PCa, iIDC-P is enriched with potentially targetable oncogenic driver mutations in MAPK/PI3K genes. Based on PTEN and ERG status, iIDC-P is not likely a precursor to the associated low-grade invasive PCa, but represents a molecularly unique in situ tumor of unclear clinical significance. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

L-type amino acid transporter 1 expression in esophageal carcinogenesis according to WHO and Japanese classifications of intraepithelial neoplasia.

L-type amino acid transporter 1 (LAT1) has an essential role in cell proliferation especially in neoplasms. Although immunohistochemical expression of LAT1 has been investigated in invasive esophageal carcinoma, its expression in intraepithelial neoplasia (IEN) has not been reported. Further, classification of esophageal IEN is currently different between the World Health Organization (WHO) and Japanese criteria. Therefore, in this study, immunohistochemical expressions of LAT1 along with Ki-67 were analyzed in 66 esophageal samples of endoscopic submucosal dissection. Extension of cells positive for either marker within the epithelium, along with LAT1 intensity at the base of the epithelium, was evaluated. The results among early IENs, progressed IENs, and invasive carcinoma based on both WHO and Japanese criteria were compared. It was demonstrated that Ki-67+ cells extended toward the superficial layer in IENs, which was more pronounced in progressed compared with early IENs based on both WHO and Japanese criteria. Although similar results were obtained for LAT1+ cells, LAT1+ cell extended more in invasive carcinoma than in progressed IENs according to the WHO criteria. Further, LAT1 intensity was different between early and progressed IENs based on the Japanese criteria alone. Thus, use of LAT1 immunohistochemistry and Japanese classification may be more meaningful to characterize esophageal carcinogenesis.

p16 Immunostaining Allows for Accurate Subclassification of Vulvar Squamous Cell Carcinoma Into HPV-Associated and HPV-Independent Cases.

The aim of this study was to compare morphologic assessment and p16 immunohistochemistry (IHC) in the determination of human papilloma virus (HPV) status in vulvar squamous cell carcinoma (VSCC). A total of 201 invasive VSCC cases were classified as "HPV-associated" when warty/basaloid VSCC or high-grade squamous intraepithelial lesion (vulvar intraepithelial neoplasia 2/3) was observed, or "HPV-independent" in the presence of well-differentiated keratinizing invasive SCC or differentiated vulvar intraepithelial neoplasia. For p16 IHC, strong nuclear and cytoplasmic staining of all cells in at least the lowermost third of the epithelium was scored as positive. All cases with discrepant HPV predictions by hematoxylin and eosin morphology versus p16 IHC were further analyzed by polymerase chain reaction for HPV DNA. On the basis of hematoxylin and eosin morphologic assessment, 50/201 tumors showed features suggestive of HPV-associated, and 47 of those showed p16 immunoreactivity (94% concordance). Of the 146 cases considered HPV-independent based on hematoxylin and eosin, 115 (79%) showed negative p16 immunostaining. Thus 83% (162/196) concordance between morphologic assessment and p16 IHC was observed, overall. In 34 cases, where morphologic assessment and p16 IHC did not agree, HPV polymerase chain reaction agreed with p16 IHC in 32/34 (94%). The sensitivity and specificity of p16 IHC in classification of VSCC as HPV-independent or HPV-associated was 100% and 98.4%, respectively. Morphologic assessment and p16 IHC are concordant in classifying VSCC as HPV-independent or HPV-associated in a majority of cases (83%). Most of the discrepant cases are p16-positive well-differentiated keratinizing VSCC, and HPV polymerase chain reaction supports classification of a large majority of these (94%) as HPV-associated. p16 IHC is validated as an accurate surrogate marker for determination of HPV status in VSCC.

Atypical proliferative endometrioid tumor of ovary: Report of a rare case.

Borderline ovarian tumors represent 10-20% of epithelial ovarian neoplasms that typically have an excellent prognosis. Both the oncological behavior of this group of tumors and also the diagnostic histological criteria are intermediate between the specific criteria of benign and malignant. They usually occur in the third to fourth decade of women's lives and are limited to the ovary in 80% of cases. Atypical proliferative or borderline ovarian tumors constitute a group of epithelial tumors with an excellent prognosis due to the low aggressiveness, microscopic examination is mandatory in order to establish an accurate histological diagnosis in all cases of borderline ovarian tumors and to differentiate from well differentiated adenocarcinoma. We report a case of a 45 year old female who presented with irregular bleeding per vaginum and underwent hysterectomy with bilateral salpingo-oophorectomy. Atypical proliferative endometrioid tumor of the left ovary was an incidental finding, which is a very rare occurrence.

[Preneoplastic lesions and precursors of urothelial cancer]. / Präneoplastische Läsionen und Vorstufen des Urothelkarzinoms.

As even a mere thickening of the urothelium can harbor genetic changes identical to that of low grade papillary urothelial tumors, it is not always possible to clearly recognize a precursor lesion of urothelial carcinoma by routine histological diagnostics. Complementary immunohistochemical and molecular diagnostic methods assist the recognition of these entities. These methods especially help to identify clinically important genetically unstable cells as the hallmark of carcinoma in situ (CIS). Little is known about the clinical significance of the morphological subtypes of CIS, which range from large cell to micropapillary variants. For a better understanding of special types of bladder cancer (e.g. adenocarcinoma and squamous cell carcinoma), it seems to be important to define the phenotype and the molecular pattern of non-urothelial lesions, such as intestinal metaplasia and squamous metaplasia, better and more precisely.

Pax2 expression in simultaneously diagnosed WHO and EIN classification systems.

PAX2 has been cited as a technically robust biomarker which nicely delineates precancerous lesions of the endometrium when the endometrial intraepithelial neoplasia (EIN) classification scheme is used. Its utility in distinguishing between atypical and nonatypical hyperplasia when applied within the 1994 World Health Organization classification system is questionable. The purpose of this study was to evaluate PAX2 in a side by side comparison of its staining patterns in a series of endometrial samples that were classified using both systems. A total of 108 precancerous endometrial cases were identified, of which 30 cases were deemed nonhyperplastic by consensus agreement and 11 cases lost the tissue of interest on deeper sections. The remaining 67 cases were categorized according to the 1994 World Health Organization criteria and EIN scheme by 2 gynecologic pathologists. PAX2 staining was scored in lesional tissue as normal or altered (lost, increased, or decreased) compared with nonlesional background. The most common pattern of alteration was complete loss of nuclear PAX2 staining (86.3%) followed by decreased staining (11.3%) and markedly increased staining (2.3%). PAX2 alterations correlated well with EIN diagnoses (33/36, 92%) compared with benign hyperplasia (2/13, 15%) but were less useful when the 1994 World Health Organization classification system was applied (PAX2 alteration in 22/25 (88%) of atypical hyperplasia cases versus 16/25 (64%) of nonatypical hyperplasia cases). Forty-five percent of follow-up hysterectomies with a previous PAX2-altered biopsy case harbored adenocarcinoma. In conclusion, PAX2 may be a helpful adjunct stain and training tool when the features of atypical hyperplasia/EIN are in question.

Incidence of serous tubal intraepithelial carcinoma (STIC) by algorithm classification in serous ovarian tumor associated with PAX8 expression in tubal epithelia: a study of single institution in Japan.

Serous ovarian carcinoma is now hypothesized to originate from fallopian tube epithelium (FTE). We investigated the FTE abnormalities in the patients with epithelial ovarian tumors. Our study included 55 cases of serous tumors (24 carcinomas, 8 borderline tumors, and 23 adenomas), 14 mucinous carcinomas, 22 endometrioid carcinomas, 5 clear cell carcinomas, and 2 malignant Brenner tumors. FTE was diagnosed by the diagnostic algorithm, which combines the data of morphology, and p53, Ki-67 immunostaining, as serous tubal intraepithelial carcinoma, serous tubal intraepithelial lesion, p53 signature, and normal/reactive. Serous tubal intraepithelial carcinoma, serous tubal intraepithelial lesion, p53 signature, and normal/reactive were observed in 5, 3, 0, and 16 cases in serous carcinoma; 0, 3, 0, and 5 cases in serous borderline tumor; 0, 1, 1, and 21 cases in serous adenoma; 0, 0, 1, and 13 cases in mucinous carcinoma; 0, 0, 3, and 19 cases in endometrioid carcinoma; 0, 0, 0, and 5 cases in clear cell carcinoma; and 0, 1, 0, and 1 case in malignant Brenner tumor. Among tumors of serous histology and between carcinomas, FTE abnormalities differed significantly (P<0.05). Serous tubal intraepithelial carcinomas were only found in serous carcinoma. The incidence of secretory cell proliferation (SCP) was examined by PAX8 expression. The rate of SCP was extremely high in serous carcinoma (96%). Among tumors of serous histology and between carcinomas, an incidence of SCP differed significantly (P<0.05). Patients with SCP were significantly older (P<0.0001). Our observations were concordant with the hypothesis of serous ovarian carcinogenesis. The SCP has a meaningful association with serous ovarian cancer.

Intraductal papillomas on core biopsy can be upgraded to malignancy on subsequent excisional biopsy regardless of the presence of atypical features.

Intraductal papillary lesions of the breast constitute a heterogeneous entity, including benign intraductal papilloma (IDP) with or without atypia and malignant papillary carcinoma. Differentiating between these diagnoses can be challenging. We re-evaluated core biopsy specimens that were diagnosed as IDP and the corresponding surgical excision specimens, and assessed the potential risk for the diagnosis to be modified to malignancy based on excision. By sorting the pathology database of the National Cancer Center Hospital, Tokyo, we identified 146 core biopsy cases that were histologically diagnosed as IDP between 1997 and 2013. The re-evaluated diagnosis was IDP without atypia in 79 (54%) patients, IDP with atypia in 66 (45%), and ductal carcinoma in situ (DCIS) in 1 (1%). Among the 34 patients (23%) who underwent surgical excision subsequent to core biopsy, histological diagnosis was upgraded to carcinoma, excluding lobular carcinoma in situ (LCIS), in 14 (41%) cases, including 4 (33%) of 12 IDPs without atypia and 10 (45%) of 22 IDPs with atypia. Complete surgical excision should be kept in mind for all IDPs diagnosed on core biopsy, not only IDPs with atypia but IDPs without atypia, especially when clinical or imaging diagnosis findings cannot rule out the possibility of malignancy, because papillary lesions comprise a variety of morphological appearances.

[VULVAR INTRAEPITHELIAL NEOPLASIA--TERMINOLOGY, SYMPTOMS AND TREATMENT].

The term vulvar intraepithelial neoplasia (VIN) was introduced for first time in 1986 year from the International Society for the Study of Vulvar Disease (ISSVD). With this term are denoted precancer vulvar conditions. According to a classification dated 1986 depending on the degree of affection of multilayered squamous epithelial vulvar precancerous lesion are subdivided into three groups: VINI, VIN2 and VIN3. Subsequently VIN1 is determinate as a lesion which there isn't oncogenic potential. These types of changes often are result from irritation or viral infection which leads to benign condylomata acuminate. Compare to lesions with VIN require histological signs for high grade intraepithelial neoplasia as nuclear pleomorphism, increased mitotic activity, atypical mitotic activity and disordered architecture of squamous cells epithelium. These fundamental morphologic characterizations lead to revision and subsequent change of the current classification. In 2004 ISSVD changed the classification. It included lesions like VIN2 and VIN3, but they are subdivided in two groups: the usual type VIN and the differentiated VIN. They have different etiology, morphology, oncogenic potential and prognosis. The usual type VIN is associated with infection of high risk types of human papilloma virus and is a more frequently met form of VIN. A very good prognosis is characteristic for it. The differentiated VIN is met in postmenopausal women of about 70 with frequency of about 2-5%. It originated from vulvar dermatosis like lichen scierosus and there is a high oncogenic potential and worse prognosis. The treatment of VIN may be surgical and by medicines. The frequency of recurrences after treatment is 30-50% which required frequently follows up. The aim of this literature review is to introduce present terminological classification of VIN, as well as basic clinical, diagnostically and curative methods in treat of the both types of this precancerous.

Reproducibility of current classifications of endometrial endometrioid glandular proliferations: further evidence supporting a simplified classification.

AIMS: To compare the reproducibility of the current (2003) World Health Organization (WHO), endometrial intraepithelial neoplasia (EIN) and European Working Group (EWG) classifications of endometrial endometrioid proliferations. METHODS AND RESULTS: Nine expert gynaecological pathologists from Europe and North America reviewed 198 endometrial biopsy/curettage specimens originally diagnosed as low-grade lesions. All observers were asked to classify the cases by using the categories described in each scheme: six for WHO, four for EIN, and three for EWG. The results were evaluated by kappa statistics for more than two observations. The analysis was repeated using only two major categories (benign versus atypical/carcinoma). Both the WHO and EIN classifications showed poor interobserver agreement (κ = 0.337 and κ = 0.419, respectively), whereas the EWG classification showed moderate agreement (κ = 0.530). Full agreement between pathologists occurred in only 28% for the WHO classification, 39% for the EIN classification, and 59% for the EWG classification. With only two diagnostic categories, kappa values increased in all classifications, but only the EWG classification reached a substantial level of agreement (κ = 0.621); similarly, full agreement among all pathologists increased to 70% for the WHO classification, 69% for the EIN classification, and 72% for the EWG classification. CONCLUSIONS: A two-tier classification of endometrial endometrioid proliferative lesions improves reproducibility, and should be considered for the diagnosis of endometrial biopsy/curettage specimens.

Evaluation of the extended Japan NBI expert team classification of subtype 2B in laterally spreading colorectal tumors based on blue laser imaging.

OBJECTIVES: The Japan NBI Expert Team (JNET) classification has good diagnostic potential for colorectal diseases. We aimed to explore the diagnostic value of the JNET classification type 2B (JNET2B) criteria for colorectal laterally spreading tumors (LSTs) based on magnifying endoscopy with blue laser imaging (ME-BLI) examination. METHODS: Between January 2017 and June 2023, 218 patients who were diagnosed as having JNET2B-type LSTs using ME-BLI were included retrospectively. Endoscopic images were reinterpreted to categorize the LSTs as JNET2B-low (n = 178) and JNET2B-high (n = 53) LSTs. The JNET2B-low and JNET2B-high LSTs were compared based on their histopathological and morphological classifications. RESULTS: Among the 178 JNET2B-low LSTs, 86 (48.3%) were histopathologically classified as low-grade intraepithelial neoplasia, 54 (30.3%) as high-grade intraepithelial neoplasia (HGIN), 37 (20.8%) as intramucosal carcinoma (IMC), and one (0.6%) as superficial invasive submucosal carcinoma (SMC1). Among the 53 JNET2B-high LSTs, five (9.4%) were classified as HGIN, 28 (52.9%) as IMC, 15 (28.3%) as SMC1, and 5 (9.4%) as deep invasive submucosal carcinoma. There were significant differences in this histopathological classification between the two groups (P < 0.001). However, there was no significant difference between JNET2B-low and JNET2B-high LSTs based on their morphological classification (granular vs nongranular) or size (<20 mm vs ≥20 mm). Besides, the κ value for JNET2B subtyping was 0.698 (95% confidence interval 0.592-0.804) between the two endoscopists who reassessed the endoscopic images. CONCLUSION: The JNET2B subtyping of LSTs has a diagnostic potential in the preoperative setting, and may be valuable for treatment decision-making.

Well-differentiated adenocarcinoma-bronchioloalveolar carcinoma-in situ adenocarcinoma: a conundrum.

Over the last decade, considerable changes have been made to the classification of pulmonary adenocarcinoma, mainly with respect to the classification of small solitary tumors. The main goal seems to have been the identification of tumors that not only follow an indolent clinical course but that can also be treated more conservatively. Thus, the most important change to the classification of lung adenocarcinoma was proposed for a tumor no greater than 3.0 cm in size with a pure lepidic growth pattern and lacking stromal, vascular, or pleural invasion, which should now be categorized as in situ adenocarcinoma. At the same time, a category of minimally invasive adenocarcinoma was proposed for tumors with a predominantly lepidic growth pattern, <3 cm in size, and with <5 mm invasion in greatest dimension in any 1 focus. What is interesting about all these developments is the fact that all the publications on this issue have been presented under the terms of small adenocarcinomas or bronchioloalveolar carcinoma. Unfortunately, the literature reviews that have proposed the change in nomenclature to in situ adenocarcinoma have not offered a more in-depth assessment of these neoplasms. More recently, a publication of a large series of cases of small adenocarcinomas has offered a different view and underscored some of the important issues that need to be taken into account before a serious change in the nomenclature can be considered.

Endocervical glandular lesions exhibiting gastric differentiation: an emerging spectrum of benign, premalignant, and malignant lesions.

A variety of benign and malignant endocervical glandular lesions exhibiting gastric differentiation has been described in the past decade that has resulted in the concept of an important category of cervical adenocarcinoma which is unrelated to human papillomavirus (HPV). Both minimal deviation adenocarcinoma (MDA), also known as adenoma malignum, and the benign lesion lobular endocervical glandular hyperplasia (LEGH), have been known for some time to exhibit a gastric phenotype and immunophenotype (HIK1083 and/or MUC6 positive). Accumulated evidence suggests that a subset of LEGH (atypical LEGH) exhibits a degree of cytologic and/or architectural atypia which, in some cases, may be associated with and be a precursor of adenocarcinomas exhibiting gastric differentiation, including MDA. Gastric-type adenocarcinoma (GAS), a recently described subtype of cervical adenocarcinoma, is an emerging clinicopathologic entity. These neoplasms exhibit a spectrum of differentiation, including MDA as its very well-differentiated form, are unrelated to HPV, and exhibit aggressive clinical behavior. It is proposed that a LEGH-GAS sequence exists and, from a practical point of view, the development of optimal biomarkers is awaited to assist in early detection of GAS and atypical LEGH, as current HPV-targeted screening generally does not detect these lesions and strategies employing HPV vaccination will not prevent their occurrence. Pathologists should be familiar with the morphologic spectrum of these benign, premalignant, and malignant cervical glandular lesions exhibiting gastric differentiation. They are occasionally associated with Peutz-Jeghers syndrome or are a component of "synchronous mucinous metaplasia and neoplasia of the female genital tract."

[The new classification of lung adenocarcinoma]. / Adenokarzinome der Lunge--die neue Klassifikation.

The new, interdisciplinary IASLC/ATS/ERS classification of lung adenocarcinoma has achieved a considerable impact since its publication in the year 2011. It separates tumours into preinvasive, minimally invasive and invasive subtypes. The preinvasive lesions atypical, adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS) together with the minimally invasive adenocarcinoma (MIA), have an excellent prognosis after complete resection with 100 % survival. It enables a reproducible tumour grading by the determination of the predominant histological growth pattern which could be confirmed in several follow-up studies. Thereby the mixed subtype was eliminated which formerly represented about 80 % of all adenocarcinomas. Similarly, the terms bronchioloalveolar adenocarcinoma and bronchioloalveolar tumour growth were eliminated because they represented several distinct entities, specifically the in-situ lesions AAH and ACIS as well as the non-in-situ/invasive tumours like minimally invasive adenocarcinoma, lepidic predominant adenocarcinoma (LPA) and invasive mucinous adenocarcinoma (IMA). Although the classification is based on data from tumour resections it accommodates the fact that most tumours are diagnosed on biopsies and cytological specimens and includes recommendations for an efficient work-up to preserve tissue for molecular testing. Furthermore, the morphological analysis may provide hints for molecular changes including mutations with therapeutic relevance that may enable targeted molecular diagnostics. This review presents essentials facts of the new classification that will be part of the next WHO classification of lung tumors and its follow-up publications.

[Aero-digestive tract squamous intra-epithelial neoplasia]. / Néoplasie intra-épithéliale épidermoïde des voies aéro-digestives supérieures.

Aero-digestive tract squamous intra-epithelial neoplasia is a disease whose genetic and epigenetic features lead to clinical signs and well codified histologic features. This publication aims to review the molecular alterations which have been identified in these lesions, to clarify the clinical manifestations and to discuss the proposed histological classification.

[Preinvasive lesions in gynecology -  vulva]. / Prekancerózy v gynekologii -  vulva.

For preinvasive lesions of vulva, a common term VIN -  vulval intraepithelial neoplasia is used. VIN is a histological dia-gnosis based on abnormal squamous epithelial proliferation. There are two types of VIN apart from their association with human papillomavirus (HPV). Undifferentiated (usual) vulval intraepithelial neoplasia is commonly associated with carcinogenic genotypes of HVP, whereas differentiated vulval intraepithelial neoplasia is not associated with high-risk genotypes of HPV. The article presents an overview of VIN occurence and epidemiology, its classification system and dia-gnostics. In conclusion, VIN therapeutical possibilities are presented. It can be treated with surgical therapy (local excision, partial vulvectomy, vulvectomy, laser vaporization) or medical therapy (imiquimod).

Assessment of invasion in lung adenocarcinoma classification, including adenocarcinoma in situ and minimally invasive adenocarcinoma.

Classification of adenocarcinoma has undergone recent evaluation to better align histological classification with clinical outcomes. One terminology, in particular, that of bronchioloalveolar carcinoma (BAC), has been debated for many decades. Although initial discussion surrounded the cell-of-origin of this tumor, more recent confusion has been generated from the use of this term both as a pattern of growth within an otherwise invasive adenocarcinoma and as a term for a pre-invasive tumor synonymous with adenocarcinoma in situ. As a result, adenocarcinomas with quite different radiology, gross morphology and metastatic potential have been associated with the BAC term. Focusing on invasion and using an illustrative case, we will explore the current recommendations that incorporate assessment of invasion to clarify the confusion caused by the different uses of the historical term 'BAC'.

Reproducibility of endometrial intraepithelial neoplasia diagnosis is good, but influenced by the diagnostic style of pathologists.

Endometrial intraepithelial neoplasia (EIN) applies specific diagnostic criteria to designate a monoclonal endometrial preinvasive glandular proliferation known from previous studies to confer a 45-fold increased risk for endometrial cancer. In this international study we estimate accuracy and precision of EIN diagnosis among 20 reviewing pathologists in different practice environments, and with differing levels of experience and training. Sixty-two endometrial biopsies diagnosed as benign, EIN, or adenocarcinoma by consensus of two expert subspecialty pathologists were used as a reference comparison to assess diagnostic accuracy of 20 reviewing pathologists. Interobserver reproducibility among the 20 reviewers provided a measure of diagnostic precision. Before evaluating cases, observers were self-trained by reviewing published textbook and/or online EIN diagnostic guidelines. Demographics of the reviewing pathologists, and their impressions regarding implementation of EIN terminology were recorded. Seventy-nine percent of the 20 reviewing pathologists' diagnoses were exactly concordant with the expert consensus (accuracy). The interobserver weighted κ values of 3-class EIN scheme (benign, EIN, carcinoma) diagnoses between expert consensus and each of reviewing pathologists averaged 0.72 (reproducibility, or precision). Reviewing pathologists demonstrated one of three diagnostic styles, which varied in the repertoire of diagnoses commonly used, and their nonrandom response to potentially confounding diagnostic features such as endometrial polyp, altered differentiation, background hormonal effects, and technically poor preparations. EIN diagnostic strategies can be learned and implemented from standard teaching materials with a high degree of reproducibility, but is impacted by the personal diagnostic style of each pathologist in responding to potential diagnostic confounders.

The significance of lobular carcinoma in situ and atypical lobular hyperplasia of the breast.

BACKGROUND: The significance of lobular neoplasia (LN), lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH)) found at core needle biopsy (CNB) of the breast remains uncertain. There is a consistent risk of underestimating malignancy after the diagnosis of LN on CNB. The aim of this study was to determine if patients with a CNB result of LN need surgical excision. METHODS: Patients were identified by searching the institutions pathology database for the terms "lobular carcinoma in situ" and "atypical lobular hyperplasia" over 20 years. Excluded from this study were those with core needle biopsy (CNB) results of ductal carcinoma in situ, atypical ductal hyperplasia, radial scar, or papilloma. Upgrade was defined as final surgical pathology of invasive carcinoma and/or ductal carcinoma in situ that was directly correlated to the site of the initial biopsy containing LN. RESULTS: LN was found at CNB in 285 patients, and 71 % (n = 201) had subsequent surgical excisions. All patients with pleomorphic LCIS (pLCIS) underwent surgical excision. Following patients with pLCIS, patients with the diagnosis of LCIS were most likely to undergo surgical excision (80 %). Final pathology of the surgically excised specimens confirmed LN in 72 % (n = 144). Also, 13 % (n = 26) of the operated patients were upgraded to malignancy, including 8 % of ALH and 19 % of LCIS cases. CONCLUSION: This is the largest series of surgical excisional pathology following LN on CNB ever reported. The likelihood of finding malignancy at surgical excision after CNB showing LN was 13 %. Patients with the diagnosis of LN on CNB should be considered for surgical excision.

Clinicopathologic correlation of ocular surface squamous neoplasms at Bascom Palmer Eye Institute: 2001 to 2010.

PURPOSE: To describe the clinical and histologic characteristics of ocular surface squamous neoplasia (OSSN) lesions and provide clinicopathologic correlation to determine clinical features that may indicate higher-grade lesions. DESIGN: Retrospective case series. PARTICIPANTS: A total of 612 consecutive OSSN lesions sent to the Bascom Palmer ocular pathology laboratory from January 1, 2001 to September 20, 2010. METHODS: Pathologic examination of lesions by a single experienced ocular pathologist (S.R.D.). Review of pathology records and patient charts. MAIN OUTCOME MEASURES: Correlation of clinical factors and histology of higher-grade OSSN. RESULTS: Over the studied period, 33% of submitted specimens were characterized as mild, moderate, or severe dysplasia; 52% were classified as carcinoma in situ; and 11% were graded as squamous cell carcinoma. Characteristics associated with higher-grade OSSN lesions included male gender, biopsy at Bascom Palmer Eye Institute, temporal and superior locations, lack of corneal involvement, papillomatous and nodular appearance, microscopic multifocality, and positive margins on biopsy. CONCLUSIONS: Certain clinical factors are associated with higher-grade histologic lesions. These findings may help clinicians more accurately evaluate and anticipate the pathologic grade of conjunctival and corneal lesions suspected to be OSSN.