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On July 7, 2020 the world of Surgical Pathology lost one of the brightest minds ever: Prof. Juan Rosai.It certainly happened to many of us while approaching a difficult case to exclaim: - This is a case for Juan Rosai! This simple expression synthesizes the legend that was created around him.Those who knew him personally were undoubtedly amazed by his diagnostic insight, exceptional memory and organizational skills.However, his vast culture and passions were not limited to medicine, but ranged to music, literature and the world of sports, especially football.We worked with him in his last years of activity and want to share with the communities of pathologists our warm feelings about this exceptional pathologist and this profound person. (read more)

In this article, we report a case of anal fibroepithelial polyp with benign squamous cell vascular pseudoinvasion. The patient was a 38-year-old Caucasian man, who presented at our institution for recurrent episodes of anal discomfort. Clinical evaluation revealed the presence of 2 pedunculated anal polyps that were resected and submitted for histological evaluation. On microscopic evaluation, one of the polyps shows epithelial endovascular displacement associated with morphological signs of traumatism. The differential diagnosis and possible pathogenetic mechanisms explaining the presence of such findings are discussed. To the best of our knowledge, this is the first case reported of an anal fibroepithelial polyp with epithelial vascular pseudoinvasion.

BACKGROUND AND AIM: A recently carried out randomized controlled trial showed the benefit of a novel 20-G fine-needle biopsy (FNB) over a 25-G fine-needle aspiration (FNA) needle. The current study evaluated the reproducibility of these findings among expert academic and non-academic pathologists. METHODS: This study was a side-study of the ASPRO (ASpiration versus PROcore) study. Five centers retrieved 74 (59%) consecutive FNB and 51 (41%) FNA samples from the ASPRO study according to randomization; 64 (51%) pancreatic and 61 (49%) lymph node specimens. Samples were re-reviewed by five expert academic and five non-academic pathologists and rated in terms of sample quality and diagnosis. Ratings were compared between needles, expert academic and non-academic pathologists, target lesions, and cytology versus histological specimens. RESULTS: Besides a higher diagnostic accuracy, FNB also provided for a better agreement on diagnosing malignancy (ĸ = 0.59 vs ĸ = 0.76, P

Objectives This study sought to evaluate the feasibility of complete cerebral protection during transcatheter aortic valve replacement (TAVR) with a novel embolic protection device. Background Evidences and data about new cerebral embolic protection devices are lacking and scarce. Methods A prospective, nonrandomized, multicenter, first-in-man pilot study designed to evaluate the efficacy and safety of cerebral embolic protection utilizing the Emblok embolic protection system (Innovative Cardiovascular Solutions, Grand Rapids, Michigan) during TAVR. The Emblok is a transfemoral aortic filter that provide full coverage of the epiaortic vessels. Brain diffusion-weighted magnetic resonance imaging (DW-MRI) was performed at baseline and 2 to 5 days after TAVR. Primary endpoints were technical success and immediate cerebral embolic burden after TAVR, defined as number and volume of new brain lesions detected with DW-MRI at days 2 to 5 post-TAVR compared with baseline. Results A total of 20 subjects were enrolled. The Emblok system was successfully positioned in all the cases. At 30-day follow-up, no major adverse cardiovascular and cerebrovascular events occurred. Nineteen (95%) patients had new ischemic defects at post-procedural DW-MRI. The median number of new lesions per patient was 10.00 (interquartile range [IQR]: 4.75 to 15.25). The total new lesion volume was 199.9 mm3 (IQR: 83.9 to 447.5 mm3) and the mean lesion volume per lesion was 42.5 mm3 (IQR: 21.5 to 75.6 mm3). Histopathologic analysis showed evidence of significant debris in 18 (90%) filters. Conclusions The Emblok embolic protection system appears to be feasible and safe during TAVR. The device was successfully placed and retrieved in all cases and no neurological events were observed. Cerebral total new lesion volume was similar to other trials on cerebral protection during TAVR, thus warranting a larger study. (European Study Evaluating the Emblok Embolic Protection System During TAVR; NCT03130491)

Extrathyroidal extension (ETE) is a significant prognostic factor in papillary thyroid carcinoma (PTC). Minimal extrathyroidal extension (mETE) is characterized by involvement of the sternothyroid muscle or perithyroid soft tissue, and is generally identified by light microscope examination. Patients with mETE, identified pathologically, are automatically upstaged to pT3. However, the prognostic implications of mETE have been a source of controversy in the literature. Moreover, there is also controversy surrounding the identification of mETE on pathological specimens. The objective of this study was to determine the level of agreement among expert pathologists in the identification of mETE in PTC cases.Eleven expert pathologists from the United States, Italy, and Canada were asked to perform a review of 69 scanned slides of representative permanent sections of PTC specimens. Each slide was evaluated for the presence of mETE. The pathologists were also asked to list the criteria they use to identify mETE.The overall strength of agreement for identifying mETE was slight (κ = 0.14). Inter-pathologist agreement was best for perithyroidal skeletal muscle involvement (κ = 0.46, moderate agreement) and worst for invasion around thick-walled vascular structures (κ = 0.02, slight agreement). In addition, there was disagreement over the constellation of histologic features that are diagnostic for mETE, which affected overall agreement for diagnosing mETE.Overall agreement for the identification of mETE is poor. Disagreement is a result of both variation in individual pathologists' interpretations of specimens and disagreement on the histologic criteria for mETE. Thus, the utility of mETE in staging and treatment of PTC is brought into question. The lack of concordance may explain the apparent lack of agreement regarding the prognostic significance of this pathologic feature.

Background: Extrathyroidal extension (ETE) by papillary and follicular thyroid carcinoma can be associated with increased risk of tumor recurrence and mortality. In the seventh edition of its Cancer Staging Manual, the American Joint Committee on Cancer (AJCC) defined minimal ETE as the involvement of skeletal muscle (i.e., strap muscles) or perithyroidal soft tissue. The eighth edition of the AJCC Cancer Staging Manual has changed the criteria so that only grossly evident (macroscopic) ETE involving strap muscles (not microscopic ETE involving perithyroidal soft tissue) affects tumor staging. Summary: Concordance of identifying microscopic ETE (as well as extranodal extension by carcinoma metastatic to lymph nodes) was previously evaluated among 11 expert endocrine pathologists. The overall agreement rate was slight when rendering a diagnosis of ETE. Concordance was highest when pathologists assessed the spatial relationship of carcinoma to skeletal muscle. This article discusses the significance of these findings. It also reviews relevant anatomic and developmental considerations related to the boundaries of the thyroid. Conclusions: The results of the concordance study provide additional rationale supporting stringent criteria for diagnosing ETE, as proposed by the eighth edition of the AJCC Cancer Staging Manual. It is expected that these rigid morphologic criteria will potentially reduce interobserver variability and enhance consistency in the diagnosis and staging of thyroid carcinoma.

Summary Oral squamous cell carcinoma (OSCC) is the most common oral cancer, and major efforts is being made to identify molecular markers capable to differentiate oral potentially malignant lesions (OPMLs) with indolent course from lesions with aggressive behavior. We undertook a study to evaluate if gain of the human telomerase RNA component (hTERC) gene in OPMLs could indicate lesions at high risk of developing OSCC. The study was performed on 30 OPMLs with long-term follow-up using a dual-color interphase fluorescence in situ hybridization (FISH) for hTERC status. Progression to malignancy was observed in 9 of 10 cases harboring hTERC gain and in 1 of 20 cases retaining a normal copy number of hTERC (P

During the course of our consultation activity, we have recognized a peculiar form of thyroiditis in which multiple foci of fibrosis, most of which were associated with reactive atypia of the surrounding follicles, are present. We have referred to this condition, both in our consultation reports and in the third series of A.F.I.P. Fascicle on Tumors of the Thyroid Gland, as "multifocal fibrosing thyroiditis" or (less frequently) "multifocal sclerosing thyroiditis," which are descriptive terms that highlight the benign/inflammatory nature of the process, its multiplicity, and its unknown pathogenesis. The aim of this study is to better define the morphologic features of this process and correlate it with some clinical data. With this purpose, the consultation files of one of the authors (J.R.) were searched for cases coded as multifocal fibrosing thyroiditis or multifocal sclerosing thyroiditis in a 20-year period ranging from January 1989 to December 2009. A total of 55 cases were identified that displayed the above-listed features. There were 51 (93%) female and 4 (7%) male patients (F/M=12.75), with ages ranging between 15 and 71 years (mean age, 47.03 y; median age, 44.5 y). Microscopically, multiple foci of fibrosis were identified in all cases, their number ranging from 2 to 51 per case (mean number, 16), with a mean diameter of 3 mm (range: 0.36 to 15.1 mm). Although heterogenous in shape and size, the individual foci were rather similar to each other in composition, being characterized by a fibrotic poorly cellular center that merged with a cellular peripheral zone. Some of the follicular structures present at the periphery of the scar and-to a lesser extent-those entrapped inside it underwent complex reactive and regenerative (atypical) changes that simulated malignancy. We discuss the differential diagnosis with other benign and malignant thyroid conditions and speculate about its pathogenesis and possible relationship with papillary thyroid microcarcinoma.

Apocrine carcinoma is a rare tumor of the skin that typically arises in areas rich in apocrine glands, such as axilla and perineum. The main differential diagnosis is a metastasis from a primary apocrine carcinoma of the breast. Several authors have attempted to define morphological and immunohistochemical parameters to differentiate metastasis from primary apocrine carcinoma of the skin, but none of these had been demonstrated to be reliable markers. Here, we report a case of primary apocrine carcinoma of the scrotum that relapsed three times within a few years, without any clinical or radiological evidence of any other tumor of breast or other sites.

Extranodal extension (ENE) in lymph node metastases has been shown to worsen the prognosis of papillary thyroid cancer (PTC). Despite the clinical significance of ENE, there are no stringent criteria for its microscopic diagnosis, and its identification is subject to inter-observer variability. The objective of this study was to determine the level of agreement among expert pathologists in the identification of ENE in PTC cases.Eleven expert pathologists from the United States, Italy, and Canada were asked to review 61 scanned slides of representative permanent sections of PTC specimens from Mount Sinai Beth Israel Medical Center in New York. Each slide was evaluated for the presence of ENE. The pathologists were also asked to report the criteria they use to identify ENE.The overall strength of agreement in identifying ENE was only fair (κ = 0.35), and the proportion of observed agreement was 0.68. The proportions of observed agreement for the identification of perinodal structures (fat, nerve, skeletal, and thick-walled vessel involvement) ranged from 0.61 to 0.997.Overall agreement for the identification of ENE is poor. The lack of agreement results from both variation in pathologists' identification of features and disagreement on the histologic criteria for ENE. This lack of concordance may help explain some of the discordant information regarding prognosis in clinical studies when this feature is identified.

The presence of “crushing” artifacts in histological sections is a very common finding and represents a potentially major pitfall for the surgical pathologist, particularly in small biopsy specimens. Microscopically, it appears as bluish clusters in which the cellular details are not recognizable. Here the authors report examples of this phenomenon that have been reported or that they have personally observed and emphasize some diagnostic clue to avoid its overinterpretation and the dire clinical consequences that this may entail.

Fine-needle aspiration (FNA) biopsies are the cornerstone of preoperative evaluation of thyroid nodules, but FNA diagnostic performance has varied across different studies. In the course of collecting thyroid FNA specimens for the development of a molecular diagnostic test, local cytology and both local and expert panel surgical pathology results were reviewed.Prospective FNAs were collected at 21 clinical sites. Banked FNAs were collected from two academic centers. Cytology and corresponding local and expert panel surgical pathology results were compared to each other and to a meta-review of 11 recently published U.S.-based thyroid FNA studies.FNA diagnostic performance was comparable between the study specimens and the meta-review. Histopathology malignancy rates for prospective clinic FNAs were 34% for cytology indeterminate cases and 98% for cytology malignant cases, comparable to the figures found in the meta-review (34% and 97%, respectively). However, histopathology malignancy rates were higher for cytology benign cases in the prospective clinic FNA subcohort (11%) than in the meta-review (6%, with meta-review rates of 10% at community sites and 2% at academic centers, p 0.0001). Resection rates for prospective clinic FNAs were also comparable to the meta-review for both cytology indeterminate cases (62% vs. 59%, respectively) and cytology malignant cases (82% vs. 81%, respectively). Surgical pathology categorical disagreement (benign vs. malignant diagnosis) was higher between local pathology and a consensus of the two expert panelists (11%) than between the two expert panelists both pre- (8%) and postconferral (3%).Although recent guidelines for FNA biopsy and interpretation have been published, the rates of false-positive and false-negative results remain a challenge. Two-thirds of cytology indeterminate cases were benign postoperatively and may decrease with the development of an accurate molecular diagnostic test. High disagreement rates between local and expert panel histopathology diagnosis suggests that central review for surgical diagnoses should be used when developing diagnostic tests based on resected thyroid specimens.

We set out to develop a molecular test that distinguishes benign and malignant thyroid nodules using fine-needle aspirates (FNA).We used mRNA expression analysis to measure more than 247,186 transcripts in 315 thyroid nodules, comprising multiple subtypes. The data set consisted of 178 retrospective surgical tissues and 137 prospectively collected FNA samples. Two classifiers were trained separately on surgical tissues and FNAs. The performance was evaluated using an independent set of 48 prospective FNA samples, which included 50% with indeterminate cytopathology.Performance of the tissue-trained classifier was markedly lower in FNAs than in tissue. Exploratory analysis pointed to differences in cellular heterogeneity between tissues and FNAs as the likely cause. The classifier trained on FNA samples resulted in increased performance, estimated using both 30-fold cross-validation and an independent test set. On the test set, negative predictive value and specificity were estimated to be 96 and 84%, respectively, suggesting clinical utility in the management of patients considering surgery. Using in silico and in vitro mixing experiments, we demonstrated that even in the presence of 80% dilution with benign background, the classifier can correctly recognize malignancy in the majority of FNA samples.The FNA-trained classifier was able to classify an independent set of FNAs in which substantial RNA degradation had occurred and in the presence of blood. High tolerance to dilution makes the classifier useful in routine clinical settings where sampling error may be a concern. An ongoing multicenter clinical trial will allow us to validate molecular test performance on a larger independent test set of prospectively collected thyroid FNAs.

The Gleason grading system is a powerful tool to prognosticate and aid in the treatment of men with prostate cancer. The needle biopsy Gleason score correlates with virtually all other pathological variables, including tumour volume and margin status in radical prostatectomy specimens, serum prostate-specific antigen levels and many molecular markers. The Gleason score assigned to the tumour at radical prostatectomy is the most powerful predictor of progression after radical prostatectomy. However, there are significant deficiencies in the practice of this grading system. Not only are there problems among practising pathologists but also a relative lack of interobserver reproducibility among experts.

A case of solitary microcarcinoid and chronic ulcerative colitis of the rectal stump is described. The association of intestinal carcinoid with ulcerative colitis has been reported previously in 26 patients. Pathogenic pathways are discussed according to the presence of multifocal carcinoid and/or gut endocrine cell hyperplasia.

We report the case of a 69-year-old man who underwent a radical left nephrectomy for a renal mass. Microscopically, the features were those of a clear cell–type renal cell carcinoma associated with 2 foci of capillary hemangioma-like vascular proliferation in the adjacent renal parenchyma. The main differential diagnosis and the possible pathogenesis of this vascular lesion are discussed.

Oral Squamous Cell Carcinoma (OSCC) is the most common tumor of the oral cavity. Approximately 500.000 new cases of OSCC are diagnosed worldwide each year with the incidence seemingly increasing. Chemo- and radiotherapy are potential curative procedures although destructive surgery is often necessary if early diagnosis is not achieved. Such procedures impact heavily on human and social costs. Infection of oral mucosa by oncogenic HPV is strongly associated with OSCC among subjects with established risk factors such as tobacco and alcohol abuse. The development of OSCC is a multistep process in which accumulated genetic and epigenetic events lead to cell cycle deregulation and chromosomal abnormalities. Gain of chromosome 3 (which contains human telomerase RNA gene, hTERC, located on chromosome 3q26) appears to be an important selective advantage in the progression of cervical intraepithelial neoplasia to invasive cancer [1] as well as in the progression to invasive head and neck carcinoma [2]. We utilized automated interphase FISH to evaluate the gain of chromosome 3 (3q26) and 7 (CEP) in oral epithelial precursor lesions in order to determine whether aneuploidy is already present and thus whether it is possible to anticipate diagnosis and clinical interventions. Retrospective in blind analysis on 40 oral samples with long-term follow up (ranging from 5 to 10 years) and with initial histological diagnosis of mild and moderate dysplasia, will be run. Preliminary results (8 samples) showed that tumor cells were already present only in the cases that progressed to cancer (4/8) [figure ​[figure1];1]; these preliminary findings confirm the usefulness of FISH as a reflex test in case of morphologically assessed pre-cancerous lesions, and highlight the potential value of this technique for early diagnosis and thus earlier treatment with less destructive therapeutic approaches. Figure 1

Lung neuroendocrine tumors are catalogued in four categories by the World Health Organization (WHO 2004) classification. Its reproducibility and prognostic efficacy was disputed. The WHO 2010 classification of digestive neuroendocrine neoplasms is based on Ki67 proliferation assessment and proved prognostically effective. This study aims at comparing these two classifications and at defining a prognostic grading system for lung neuroendocrine tumors. The study included 399 patients who underwent surgery and with at least 1 year follow-up between 1989 and 2011. Data on 21 variables were collected, and performance of grading systems and their components was compared by Cox regression and multivariable analyses. All statistical tests were two-sided. At Cox analysis, WHO 2004 stratified patients into three major groups with statistically significant survival difference (typical carcinoid vs atypical carcinoid (AC),P=0.021; AC vs large-cell/small-cell lung neuroendocrine carcinomas,PP=0.021; and G2 vs G3,P≤0.001), mitotic count (G1 ≤2, G2 >2–47, G3 >47; G1 vs G2,P≤0.001; and G2 vs G3,P≤0.001), and presence of necrosis (G1 absent, G2 10% of sample; G1 vs G2,P≤0.001; and G2 vs G3,P≤0.001) at uni and multivariable analyses. The combination of these three variables resulted in a simple and effective grading system. A three-tiers grading system based on Ki67 index, mitotic count, and necrosis with cutoffs specifically generated for lung neuroendocrine tumors is prognostically effective and accurate.

Today the “whole slide images” (virtual slides) is an important tool also in clinical microbiology. Virtual microscopy consists of digitizing a glass slide acquiring hundred of tiles of areas of interest at different resolution levels, and assembling them in a structured file. We shortly report the key elements of this technology from the acquisition of the image using a scanner, to the broadcasting of virtual slides to a distant viewer over an internet connection.

Eccrine porocarcinoma is a potentially fatal form of sweat gland carcinoma, due to its propensity to metastasize through lymph vessels. The authors report the case of a 69-year-old female who presented with swelling of the right leg and an ulcerated lesion of the right great toe. The initial histologic diagnosis was invasive squamous cell carcinoma. On follow-up, the patient developed lymphangitic tumor spread in the right leg, associated with right inguinal lymphadenopathy and lesions in vulva and flank. Reevaluation of the toe lesion led to a revised diagnosis of eccrine porocarcinoma. The patient also had 2 basal cell carcinomas of the multicentric/superficial type in the skin overlying the left breast. Past history included chronic ingestion of liquore arsenic (Fowler’s solution) in early adulthood as treatment for dermatitis herpetiformis.

The occurrence of various types of heterotopic epithelial structures in lymph nodes is a well-documented phenomenon. Here, we report on the presence of such inclusions in axillary lymph nodes. A total of 18 cases were identified. All patients were women, their ages ranging from 32 to 79 years (median, 57 y). Thirteen patients had concomitant or antecedent breast abnormalities, and 12 of them had undergone nodal sampling for staging purposes. The other 5 patients had noted enlarging axillary masses, with no clinical evidence of previous or concomitant breast or genital tract pathology. We classified the nodal inclusions on morphologic grounds into 3 main categories: those composed exclusively of glandular structures (glandular-type inclusions; 10 cases, 56%); those made up only of squamous cysts (squamous-type inclusions; 2 cases, 11%); and those containing both glandular and squamous epithelia (mixed glandular-squamous-type inclusions; 6 cases, 33%). We speculate about the possible mechanism for the migration of the epithelial cells into the lymph nodes, discuss the modifications that they may later undergo as a result of local and systemic factors, and consider the differential diagnosis with other conditions, particularly with metastatic well-differentiated breast carcinoma.

Sarcomatoid change in renal cell carcinoma is the result of the dedifferentiation of the “parent” tumor into a high-grade malignancy characterized by sarcoma-like features and associated with an accelerated clinical course and poorer prognosis. Any of the renal cell carcinoma subtypes can undergo sarcomatoid dedifferentiation, with the chromophobe variant being the most prone. The present report describes the case of a woman affected by a classic chromophobe renal cell carcinoma that developed dedifferentiation accompanied by a very rare osteosarcoma-like divergent differentiation, which constituted about 90% of the entire retroperitoneal mass. In addition to presenting the relevant imaging, histopathological, and immunohistochemical findings, this article briefly discusses the main differential diagnosis of retroperitoneal ossifying/ calcifying masses, which could give rise to diagnostic problems either in small biopsies or at imaging.

A 58-year-old woman underwent a curative total abdominal hysterectomy with bilateral salpingo-oophorectomy for a uterine carcinosarcoma. Fifteen months later, PET and CT scan revealed three pulmonary nodules and multiple lymphadenopathy. An atypical lung segmentectomy with dissection of the regional lymph nodes was performed. Two of the three nodules showed morphological and immunohistochemical profiles consistent with the diagnosis of large-cell neuroendocrine carcinoma (LCNEC). The third nodule, the surrounding pulmonary parenchyma and lymph nodes showed diffuse sarcoid granulomatosis. Re-review of the histology of the uterine carcinosarcoma revealed LCNEC morphology with immunohistochemical and genetic profiles identical to the lung cancers, finally deemed as metastatic deposits. Systemic sarcoidosis was ruled out. To our knowledge this is the first case of uterine carcinosarcoma with LCNEC features metastatic to the lung and occurring in association with sarcoid reaction.

An ovarian mature cystic teratoma featuring florid vascular proliferation and Wagner-Meissner—like corpuscles is presented. The vascular proliferation is analogous to that seen in other tumors having a prominent neural component. The Wagner-Meissner—like corpuscles are viewed as evidence of a specialized type of differentiation of this neural component. To the best of our knowledge, they had not been previously reported in this setting.

The role of Wnt pathway in digestive endocrine tumours is debated. The aim of this work is to investigate key players in Wnt pathway by a multimodal approach. Sixty cases (49 well-differentiated and 11 poorly differentiated) were investigated for methylation of adenomatous polyposis coli (APC) and E-cadherin promoters, the loss of heterozygosity (LOH) at APC locus and b-catenin and E-cadherin expression by immunohistochemistry. Tumours showing altered b-catenin localization were tested for b-catenin and APC mutations. APC promoter methylation was restricted to gastroduodenal tumours (21 out of 59, 36%), prevalent in poorly differentiated carcinomas (PZ0.042) and correlating with aggressive features (high histology grade, P!0.02; tumour death, PZ0.026; high fractional allelic loss, PZ0.002, in turn correlating with short survival, PZ0.017). LOH at APC locus was found in 14 out of 53 cases (26%, 10 gastroduodenal and 4 colorectal), prevalent in poorly differentiated carcinomas (PZ0.002) and correlating with histology grade (PZ0.012). b-catenin abnormal expression was found in 41 out of 54 cases (76%), with nuclear staining correlating with APC alteration (PZ0.047) and short survival (PZ0.006). APC, but not b-catenin, gene mutations were found (7 out of 35 tumours), 4 of which in the midgut.E-cadherin promoter methylation was rarely detected (2 out of 52 cases), with cytoplasmic expression in 18 out of 43 cases (42%), not correlating with any clinico-pathological feature. In conclusion, Wnt pathway alterations, as represented by abnormalb-catenin localization, are common events in digestive endocrine tumours, but only nuclear expression correlates with tumour aggressiveness. Though with different alteration mechanisms according to anatomical site, APC plays a major role in Wnt pathway activation and in determining the high chromosomal instability observed in aggressive endocrine carcinomas. Endocrine-Related Cancer (2008) 15 1013–1024

Combined nonneuroendocrine–neuroendocrine lung tumors are relatively infrequent and little is known as for their genetic basis. Here, we report the case of a 69-year-old male with a solitary neoplasm in the upper lobe of the right lung. At histological examination, the tumor showed two components. The main part was an adenocarcinoma of the acinar type. The second part showed morphological and immunohistochemical phenotype of a neuroendocrine carcinoma composed of a small cell lung carcinoma and a large cell neuroendocrine carcinoma. The aim of our study was to investigate the genetic relationship between neuroendocrine and nonneuroendocrine tumor components. To this purpose, we performed a loss of heterozygosity (LOH) analysis with 40 chromosomal microsatellite markers. Microallelotyping revealed a common genetic profile in the different tumor areas. In 9 of 30 informative regions analyzed, LOH involved the same allele in all components, regardless of their histological type and grade. These findings support the true combined nature of this exocrine–neuroendocrine carcinoma of the lung and suggest a common monoclonal origin from a pluripotent epithelial (alveolar or bronchial) precursor cell for the two different tumor components.

The gastrointestinal endocrine tumors are neoplastic lesions with often elusive malignant clinical behavior. The current WHO classification attempted to define a more effective approach by introducing the concepts of cell differentiation and site-specific malignancy, as well as specific criteria for carcinoma definition. WHO clinicopathological correlations embed the prognostic features: degree of cell differentiation, angioinvasion, proliferation fraction as assessed by mitotic index and Ki67, size, and functional activity. Other prognostic variables have been recognized, most of which related to specific biological features of neuroendocrine cancer cells. Nonetheless, the presence of liver or distant metastases are the prognostic variables ultimately determining the patients’ fate in terms of survival and/or therapy response. A recent proposal of tumor grading and tumor, nodes, and metastases (TNM) staging aims at a simple and practical system for patients stratification. Application of such proposal should be implemented in routine clinical practice.

Synchronous triple lung tumours are rare and little is known as for their genetic basis. Here we report a case of a 59 years old male with three synchronous independent and histological different primary tumours of the left lung. Two nodules were located in the upper lobe and consisted of an adenocarcinoma (ADC) and an endobronchial poorly differentiated squamous cell carcinoma (SCC). A third nodule of the lower lobe corresponded to a small cell neuroendocrine carcinoma (SCLC). To assess if they represented independent primary tumours and have common genetic profiles, tumours were investigated for loss of heterozygosity (LOH) at 40 chromosomal markers. A comparable fractional allelic loss of 0.52 was observed in the ADC and SCLC, while it was 0.28 in the SCC. Microallelotyping analysis did not reveal a common genetic profile, supporting the hypothesis that the three synchronous tumours are truly independent primaries with different histogenesis.

Medullary sponge kidney (MSK) is an uncommon benign congenital disorder, generally asymptomatic. In symptomatic patients the diagnosis is usually made by excretory urography performed in the most frequent complications such as renal stones, urinary tract infections and haematuria. Excretory urography can be very characteristic, showing cystic collections of ectatic collecting ducts like "bunches of grapes" or "bouquet of flowers". When haematuria represents the only symptom, and radiographic findings are not characteristic of MSK, the differential diagnosis with a renal tumor can be very difficult. We report a case of MSK that underwent nephrectomy since clinical and radiological features mimicked a renal tumor.

We describe the case of a 50-year-old male who underwent total thyroidectomy bec ause of clinical suspicion of medullary thyroid carcinoma, due to persistent elevation of the serum calcitonin level (up to 23 pg/mL). Grossly, the thyroid had a multinodular appearance consistent with nodular hyperplasia (adenomatoid goiter). Microscopically, the sections taken from the isthmus showed a multinodular structure composed of well-defined epithelial nests with peripheral palisading resembling transitional epithelium (urothelium). Most of the nests were solid, but there were also cystic formations containing mucin. These epithelial nests were interspersed between the thyroid follicles and sometimes merged with them. Immunohistochemically, the nests displayed strong nuclear positivity for p63 and cell membrane staining for cytokeratin 5/6, International Journal of Surgical Pathology olume 17 Number 3 June 2009 268-269 © 2009 The Author(s) 10.1177/1066896909333747 http://ijsp.sagepub.com “Giant” Solid Cell Rest of the Thyroid: A Hyperplastic Change?

Clinical management of thyroid neoplasms is based on light microscopic diagnosis, but its accuracy and precision are poorly defined.To assess inter- and intraobserver variability of preoperative cytopathologic and postoperative histopathologic thyroid diagnoses.Samples were collected in a prospective, multicenter trial validating a gene expression classifier between June 2009 and December 2010.14 academic and 35 community clinical sites.653 patients with 776 surgically resected thyroid nodules of 1 cm or greater.Intraobserver concordance among 2 or more central histopathologists who independently read histopathology slides was calculated. Interobserver concordance between the diagnoses made by the central histopathologists and those made by local pathologists were calculated. Intra- and interobserver concordance for cytopathology was similarly calculated by comparing diagnoses made by local pathologists with those made by a central panel of 3 cytopathologists.Concordance on the histopathologic distinction between benign and malignant diagnoses was 91% comparing local with central histopathologists and 90% comparing 2 central histopathologists. Using the 6-category Bethesda System, 64.0% of diagnoses made by local and central cytopathologists and 74.7% of intraobserver diagnoses were concordant. Central cytopathologists made fewer indeterminate diagnoses than local pathologists (41.2% vs. 55.0%).Many local pathologists did not use the Bethesda System, so their reports were translated to allow comparison. The study required histopathology, and the study population and specimens did not encompass all newly evaluated patients with a thyroid nodule.Substantial inter- and intraobserver variability exists in the cytopathologic and histopathologic evaluation of thyroid nodules, confirming an inherent limitation of visual microscopic diagnosis.Veracyte.