Aß Amyloid Scaffolds the Accumulation of Matrisome and Additional Proteins in Alzheimer's Disease.

We report a highly significant correlation in brain proteome changes between Alzheimers disease (AD) and CRND8 APP695NL/F transgenic mice. However, integrating protein changes observed in the CRND8 mice with co-expression networks derived from human AD, reveals both conserved and divergent module changes. For the most highly conserved module (M42, matrisome) we find many proteins accumulate in plaques, cerebrovascular amyloid (CAA), dystrophic processes, or a combination thereof. Overexpression of two M42 proteins, midkine (Mdk) and pleiotrophin (PTN), in CRND8 mice brains leads to increased accumulation of A ß ; in plaques and in CAA; further, recombinant MDK and PTN enhance A ß ; aggregation into amyloid. Multiple M42 proteins, annotated as heparan sulfate binding proteins, bind to fibrillar A ß 42 and a non-human amyloid fibril in vitro. Supporting this binding data, MDK and PTN co-accumulate with transthyretin (TTR) amyloid in the heart and islet amyloid polypeptide (IAPP) amyloid in the pancreas. Our findings establish several critical insights. Proteomic changes in modules observed in human AD brains define an A ß ; amyloid responsome that is well conserved from mouse model to human. Further, distinct amyloid structures may serve as scaffolds, facilitating the co-accumulation of proteins with signaling functions. We hypothesize that this co-accumulation may contribute to downstream pathological sequalae. Overall, this contextualized understanding of proteomic changes and their interplay with amyloid deposition provides valuable insights into the complexity of AD pathogenesis and potential biomarkers and therapeutic targets.

Pulmonary Adenocarcinoma, Intra-alveolar Variant: A Rare Entity Mimicking Desquamative Interstitial Pneumonia.

Exclusive discohesive tumor cells within intra-alveolar spaces is a rare pattern of involvement of primary and metastatic lung tumors. In the absence of a tumoral mass, this pattern closely mimics desquamative interstitial pneumonia (DIP) clinically, radiologically, and histologically. However, a secondary DIP pattern may be seen adjacent to a tumor mass not infrequently. Here, we describe a case of a 64-year-old woman status post bilateral lung transplantation, who was radiologically thought to have an interstitial lung disease. The autopsy lung specimen revealed extensive involvement by intra-alveolar adenocarcinoma, with a cytomorphology mimicking alveolar macrophages as seen in DIP in the absence of a tumoral mass. The presence of subtle clustering with signet ring cell features and rare micropapillae were an important clue to the diagnosis. The tumor cells were positive for CK7, napsin-A, and TTF-1, and negative for CD68. This case represents an unusual variant of pulmonary adenocarcinoma with a pure intra-alveolar pattern of involvement, mimicking DIP. To the best of our knowledge, excluding biopsy specimens, only one similar case has been reported in the literature and none in the posttransplant setting.

Chondrosarcoma-like metastasis from a poorly differentiated uterine cervical squamous cell carcinoma. A unique morphology and diagnostic pitfall in cytology.

Rare cases of metastatic squamous cell carcinoma with chondroid differentiation from esophageal primary have been reported but none from the uterine cervix. Given the rarity of this phenomenon and potential diagnostic pitfall, we present this unusual case. The patient is a 25-year-old woman who presented with shortness of breath. Computerized tomography (CT) showed several lung and pleural-based nodules. CT-guided core biopsy with touch preparations were performed on the pleural-based nodule. The touch preparations showed large, spindle-to-oval shaped cells with pleomorphic nuclei embedded in metachromatic chondroid stroma. The core biopsies also showed predominantly round-to-spindle shaped cells with hyperchromatic nuclei and prominent nucleoli embedded in a cartilaginous matrix. Her past medical history is significant for a poorly differentiated squamous cell carcinoma of the cervix, which on review showed a typical non-keratinizing squamous cell carcinoma without sarcomatous differentiation. Immunohistochemical stains performed on the pleural-based mass showed tumor positivity for AE1/AE3, CK5/6, p16, and S-100. Similar results were seen when the cervical tumor was stained retrospectively. Human papilloma virus (HPV) in situ hybridization performed on both the pleural-based mass and cervical tumor detected the presence of high-risk HPV subtypes including 16 and 18. These findings supported a lung metastasis from the prior cervical carcinoma. This case emphasizes that cervical carcinoma can develop mesenchymal (chondrosarcomatous) differentiation in metastasis even in tumors presenting with pure epithelial phenotype. Awareness of this occurrence especially on limited cytology material, knowledge of the prior history and use of ancillary tests are extremely helpful in arriving at the correct diagnosis. Diagn. Cytopathol. 2017;45:750-753. © 2017 Wiley Periodicals, Inc.

Breast adenomyoepithelioma and adenomyoepithelioma with carcinoma (malignant adenomyoepithelioma) with associated breast malignancies: A case series emphasizing histologic, radiologic, and clinical correlation.

The 2012 World Health Organization (WHO) classification of breast tumors distinguishes adenomyoepitheliomas (AMEs) as benign tumors composed of a biphasic proliferation of phenotypically variable myoepithelial cells around small epithelial lined spaces. Many AMEs have demonstrated benign behavior and are often cured with excision with negative margins, but some have exhibited malignant transformation of the myoepithelial cells, ductal epithelial cells, or both. When one of the components is histologically malignant, it is termed AME with carcinoma. Due to the rarity, the literature correlating imaging, histology, and clinical outcome is limited. A retrospective review was undertaken. A review of an institutional pathology database identified 14 cases with AME or malignant AME. Most AMEs had nonspecific imaging findings and were categorized as Bi-Rads 4. Histologic features of AME did not correlate with prior or concurrent breast malignancies or any radiographic features. Clinical follow up could be obtained for all but one case (mean follow up time = 75 months). 5 cases had no known treatment post-biopsy and 5 patients received mastectomy. No recurrences were noted. 3/13 cases of benign AME had associated breast malignancies including invasive ductal adenocarcinoma and ductal carcinoma in-situ. 1 case of malignant AME had a synchronous separate malignant phyllodes tumor. Given the unclear and unpredictable propensity for malignant transformation, conservative excision with negative margins currently seems appropriate.

CD44 Expression Level and Isoform Contributes to Pancreatic Cancer Cell Plasticity, Invasiveness, and Response to Therapy.

PURPOSE: A subpopulation of pancreatic ductal adenocarcinoma (PDAC) cells is thought to be inherently resistant to chemotherapy or to give rise to tumor cells that become resistant during treatment. Here we determined the role of CD44 expression and its isoforms as a marker and potential target for tumor cells that give rise to invasive and gemcitabine-resistant tumors. EXPERIMENTAL DESIGN: RT-PCR, Western blotting, and DNA sequencing was used to determine CD44 isoform and expression levels. Flow cytometry was used to sort cells on the basis of their CD44 expression level. CD44 expression was knocked down using shRNA. Tumorigenic properties were determined by clonogenic and Matrigel assays, IHC, tumor growth in vivo using luciferase imaging and by tumor weight. RESULTS: We identified an invasive cell population that gives rise to gemcitabine-resistant tumors. These cancer cells express a high level of CD44 standard isoform and have an EMT phenotype (CD44s/EMT). In vivo, CD44s/EMT engraft and expand rapidly and give rise to tumors that express high levels of CD44 isoforms that contain multiple exon variants. CD44low-expressing cells show continued sensitivity to gemcitabine in vivo and knockdown of CD44 in CD44s/EMT cells increases sensitivity to gemcitabine and decreases invasiveness. CONCLUSIONS: PDAC cells expressing high levels of CD44s with a mesenchymal-like phenotype were highly invasive and developed gemcitabine resistance in vivo Thus, initial targeting CD44 or reversing the CD44high phenotype may improve therapeutic response. Clin Cancer Res; 22(22); 5592-604. ©2016 AACR.

Cytologic findings of NUT midline carcinoma in the hilum of the lung.

Nuclear protein in testis (NUT) midline carcinoma (NMC) is a clinically lethal malignancy affecting all age group often located in the midline structures such as mediastinum, larynx and nasopharynx. It is characterized by chromosomal translocation between chromosomes 15 and 19 with the formation of chimeric gene BRD-NUT. We present the cytologic findings of NMC including the immunohistochemical stains performed. The patient is a 34-year-old man who presented with 1 month history of dyspnea and interscapular pain followed by nonproductive cough a week before consultation. He was initially diagnosed with pneumonia. Due to progression of symptoms, a chest CT scan was performed revealing a large hilar mass and mediastinal adenopathy. A core biopsy with touch preparations of the hilar mass was performed which revealed cohesive malignant cells with ovoid to elongated nuclei, fine to coarse chromatin pattern, irregular nuclear contour, prominent nucleoli, and scant ill-defined cytoplasm arranged in sheets and focally pseudoglandular pattern. Although focal nuclear overlapping and crush artifact were identified, karyorrhectic debris and mitotic figures were rare. Squamous differentiation was absent. The core biopsy showed discohesive malignant cells with tumor necrosis. No nuclear molding, glandular or squamous differentiation was identified. The tumor was immunoreactive for p63 and NUT with high Ki-67 (>80%). The tumor was negative for keratin, lymphoid, myeloid, neuroendocrine markers and S-100. This case emphasizes that cytologic features of NMC can mimic poorly differentiated, undifferentiated and neuroendocrine carcinomas and the importance of immunohistochemical stains especially NUT monoclonal antibody in arriving at the diagnosis.

Incidence and aetiologies of pulmonary granulomatous inflammation: a decade of experience.

BACKGROUND AND OBJECTIVE: Granulomatous lung disease (GLD) is caused by a wide range of conditions. Often there is a need to correlate pathological findings with clinical, microbiological or radiological data to determine an aetiology. The aim of this study was to determine the different aetiologies of GLD over the past decade. METHODS: Among 2228 consecutive lung specimens from 1999 to 2011, 226 cases (10.1%) were positive for GLD. One hundred ninety patients were retrospectively reviewed and diagnoses were assigned based on availability of histological/clinical/microbiological correlation. RESULTS: A confident, probable and uncertain diagnosis was made in 68.4%, 13.2% and 18.4% patients. The aetiologies comprised infectious, non-infectious and uncertain in 54.7%, 26.8% and 18.4% patients. Mycobacterial infections constituted 27% of all patients, and included atypical, tuberculous and unclassified mycobacteria in order of frequency. Acid-fast bacilli (AFB) were visualized in tissue sections in 29% cases and cultured in 73% cases. Fungal infections comprised 27% of all cases, which included Coccidioides, Cryptococcus, Aspergillus and Histoplasma in order of frequency. Fungi were visualized in tissue sections with Gomori methenamine silver (GMS) stain in 83% patients and cultured in 52% cases. Sarcoidosis was the major non-infectious aetiology, constituting 21% of all patients. Necrosis in granulomas was associated with the presence of infection (P < 0.001). CONCLUSIONS: The aetiology in necrotizing GLD with negative AFB and GMS stains is most likely infectious due to atypical mycobacteria. Coccidioidomycosis was the most common fungal infection. The aetiology in non-necrotizing GLD is most likely non-infectious, probably sarcoidosis.

Cardiac inflammatory myofibroblastic tumor: a comprehensive review of the literature.

Although inflammatory myofibroblastic tumors (IMTs) can be found in virtually every major organ, cardiac origin is rare. After recently providing care to a child who presented with a significant myocardial infarction, interest in this rare tumor was piqued. We describe a comprehensive review of cardiac IMT, including information on nomenclature, epidemiology, clinical features, pathogenesis, gross/histological features, immunohistochemical profile, diagnosis, treatment, and prognosis. Fifty-seven cases were identified in the literature. Interestingly, our case represents the seventh case of coronary artery involvement reported. Moreover, it was found that an initial presentation of sudden death most commonly involves the coronary arteries.

Lung adenocarcinoma biomarker incidence in Hispanic versus non-Hispanic white patients.

CONTEXT: Lung cancer is the leading cause of cancer deaths in the United States and worldwide. Biomarker testing is critical to personalized therapy in lung adenocarcinoma and has been extensively investigated in non-Hispanic whites, Asians, and African Americans. However, little information addresses the underlying genetic changes in lung adenocarcinoma among Hispanic patients in the United States. OBJECTIVE: To identify targetable biomarkers other than EGFR and EML4-ALK in Hispanic patients with lung adenocarcinoma. DESIGN: We tested DNA extracted from 85 lung adenocarcinoma specimens collected from 40 Hispanic and 43 non-Hispanic white patients for previously reported mutations in KRAS, MET, BRAF, mTOR, STAT3, JAK2, PIK3CA, AKT1 through AKT3, and PTEN with a custom Sequenom massARRAY assay (Sequenom, San Diego, California). RESULTS: Mutations in KRAS were identified in 11 cases (13%; 6 Hispanic [7%], 5 non-Hispanic white [6%]) and had no correlation with sex, age, or smoking history. Mutations in PIK3CA were identified in 2 of the 40 Hispanic patients (5%), including one patient (2.5%) with a concurrent KRAS mutation. The tumors were wild type for all other genes tested. CONCLUSIONS: Targetable biomarkers other than EGFR and EML4-ALK were identified in 7 of the 40 Hispanic patients (18%) and 5 of the 43 non-Hispanic white patients (12%), suggesting a similar mutational frequency. Our highly multiplexed genotyping assay detected actionable mutations in 14% (12 of 83) more patients than would have been identified by EGFR and EML4-ALK testing alone.

EGFR mutations in US Hispanic versus non-Hispanic white patients with lung adenocarcinoma.

CONTEXT: Lung cancer is the leading cause of cancer deaths worldwide. First-generation tyrosine kinase inhibitors improve progression-free survival in lung cancers with epidermal growth factor receptor (EGFR) mutations. EGFR mutations occur predominantly in exons 19 and 21 in lung adenocarcinomas of Asians (∼30%), whites (∼15%), and African Americans (∼19%). However, minimal information exists on the prevalence or type of genetic changes that occur in lung cancers in US Hispanic patients. We investigated the EGFR mutation frequency in primary lung adenocarcinomas in US Hispanics compared with non-Hispanic whites. OBJECTIVE: To evaluate EGFR mutations in lung adenocarcinomas from US Hispanic patients compared with those from non-Hispanic white patients. DESIGN: DNA samples were extracted from paraffin-embedded tissue of consecutive lung adenocarcinomas from 83 patients. Samples were collected from 40 Hispanics and 43 non-Hispanic whites. Mutations in EGFR were analyzed using a custom assay. Results.-Fourteen of 83 patients (16.9%) had EGFR mutations in their tumor DNA, including 6 of 40 Hispanics (15.0%) and 8 of 43 non-Hispanic whites (18.6%). No association with age, sex, or tumor stage was identified. Smoking history could not be obtained for most of the 83 patients, although 8 of the 11 patients with EGFR mutations for whom smoking history was obtained were nonsmokers. Most of the tumors with EGFR mutations (12 of 14; 85.7%) were acinar with lepidic or papillary subtypes. EGFR mutations occurred in exon 19 (42.8%), exon 18 (28.6%), exon 20 (28.6%), and exon 21 (14.3%). Two cases had 2 mutations identified in different exons. CONCLUSION: The frequency of EGFR mutations is similar in US Hispanics compared with non-Hispanic whites.

Tissue-preserving antibody cocktails to differentiate primary squamous cell carcinoma, adenocarcinoma, and small cell carcinoma of lung.

CONTEXT: With the availability of cell type-specific therapies, differentiating primary lung squamous cell carcinomas (SCCs) and adenocarcinomas (ACAs) has become important. The limitations of small sample size and the need to conserve tissue for additional molecular studies necessitate the use of sensitive and specific marker panels on a single slide. OBJECTIVE: To distinguish SCC from ACA and small cell carcinoma (SmCC) of lung using 2 novel tissue-conserving cocktails. DESIGN: We compared two antibody cocktails, desmoglein 3 + cytokeratin 5/napsin A and p40/thyroid transcription factor 1 (Biocare Medical, Concord, California) in diagnosing SCC and ACA of the lung on tissue microarray, cytology, and surgical specimens. Both lung and nonlung tissue were evaluated on an 1150-core tissue microarray that contained 200 lung cancers. A microarray of 35 SmCCs and 5 small cell SCCs was also evaluated. RESULTS: A cocktail of desmoglein 3 + cytokeratin 5/napsin A provided diagnostic accuracy in lung cancers with a sensitivity and specificity of 100% in SCCs and a sensitivity of 86% and a specificity of 100% in ACAs. A p40/thyroid transcription factor 1 cocktail showed p40 to have a specificity of 92% and a sensitivity of 93% in SCCs, whereas thyroid transcription factor 1 had a specificity of 100% and a sensitivity of 77% in ACAs. Cell blocks of fine-needle aspiration cytology compared with corresponding surgical (n = 20) specimens displayed similar findings. The p40 was useful in differentiating bladder from prostate carcinoma with 88% sensitivity. Isolated carcinomas from nonlung tissues were desmoglein 3 + cytokeratin 5 positive. Napsin A was positive in 22% of renal tumors as previously observed. Both cocktails were excellent in differentiating SmCCs and small cell SCCs because none of the SmCCs stained with p40. CONCLUSIONS: Both antibody cocktails are excellent in differentiating primary lung ACA from SCC, as well as excluding SmCC and ACAs from all other sites on small specimens. A cocktail of desmoglein 3 + cytokeratin 5/napsin A is slightly superior compared with p40/thyroid transcription factor 1 cocktail.

Cystic lung lesions in Sjogren syndrome: analysis of lymphocyte subsets in tissue with clinico-radiologic-pathologic correlation.

Pulmonary complications associated with Sjögren syndrome (SS) have attracted attention in recent years. Sjögren syndrome has been associated with small cyst formation in salivary glands, thymus, and lungs and has been recently brought to the forefront by radiologists due to high-resolution techniques. However, pathologists are less aware of this finding unless clinico-radiologic-pathologic correlation is sought. Formation of large bullae in SS is a rare complication with potential for confusion with other diseases. Here, we present the clinical, radiologic, and pathologic findings in 3 patients with SS associated with multiple pulmonary cystic lesions. All 3 patients had a variable mixed restrictive and obstructive component of the disease. There was good correlation with the pulmonary function tests (PFTs), high-resolution computed tomographic scan, and morphology with regard to the restrictive component. The small cysts appear to correlate with the extent of obstructive changes on the PFTs. However, the large bullae do not, implying noncommunication with the conducting airways. This noncorrelation between the PFTs and extent of bullous disease with predominant involvement of lower lobes in SS enables distinction from bullous emphysema. The mechanism of bulla formation in SS appears to be different from bullous emphysema. A check valve mechanism has been proposed previously in SS, which does not explain cyst formation in the thymus. Alternately, inflammation may play a role with the key suspects being CD4 T-helper cells and perhaps NK cells. This is the first report of a clinico-radiologic-pathologic correlation with analysis of lymphocyte subsets.

Two cases of endobronchial carcinoid masked by superimposed aspergillosis: a review of the literature of primary lung cancers associated with Aspergillus.

We describe 2 cases of endobronchial pulmonary carcinoid tumor with superimposed Aspergillus colonization. The Aspergillus hyphae were associated with fibrin, ulcer debris, and granulomatous inflammation in part masking the carcinoid tumor. Presence of necrotic debris made diagnosis on biopsy difficult, and atypical carcinoid could not be ruled out. The association of carcinoid tumor with aspergillosis is rare and has been reported in 4 other cases thus far. A review of the literature reveals at least 35 cases of lung carcinoma with coexisting Aspergillus upon presentation. Most of these carcinomas are either cavitary squamous cell or adenocarcinomas harboring an aspergilloma. The other carcinomas are associated with bronchial obstruction as in carcinoids or are a minor component of a preexisting cavity raising the possibility of "scar carcinoma." As in aspergillomas not associated with carcinoma, upper lobe involvement predominates. Diagnosis can be challenging with delayed discovery of underlying neoplasm leading to suboptimal treatment.

Evaluation of napsin A, cytokeratin 5/6, p63, and thyroid transcription factor 1 in adenocarcinoma versus squamous cell carcinoma of the lung.

CONTEXT: The distinction of lung adenocarcinoma from other types of primary lung malignancies is important clinically. Accurate morphologic classification is often hindered because 70% of lung cancers are diagnosed on limited fine-needle aspiration or transbronchial biopsy specimens. Although thyroid transcription factor 1 (TTF-1) has historically been the most specific marker for lung adenocarcinoma, a relatively new marker, napsin A, has recently been shown to be more sensitive and specific than TTF-1. OBJECTIVE: To find the most cost-effective panel to reliably distinguish lung adenocarcinoma from squamous cell carcinoma. DESIGN: A total of 291 lung cancers were evaluated morphologically (197 adenocarcinomas [75%]; 66 squamous cell carcinomas [25%]; 28 cases could not be classified into either and were dropped). Immunohistochemistry for napsin A, Cytokeratin 5/6, p63, and TTF-1 was performed on a formalin-fixed tissue microarray obtained from Toyama, Japan. Cases were scored as positive or negative against a negative control. RESULTS: Napsin A had 83% sensitivity and 98% specificity and TTF-1 had 60% sensitivity and 98% specificity for adenocarcinoma. Cytokeratin 5/6 had 53% sensitivity and 96% specificity and p63 had 95% sensitivity and 86% specificity for squamous cell carcinoma. A panel of napsin A and p63 has a specificity of 94% and a sensitivity of 96% for distinguishing adenocarcinoma from squamous cell carcinoma. CONCLUSIONS: The source of the antibody is important in avoiding false-negative results. The most cost-effective tissue-preserving panel for small biopsy specimens in the differential diagnosis of lung adenocarcinoma versus squamous cell carcinoma is a combination of p63 and napsin A.

Napsin A, a new marker for lung adenocarcinoma, is complementary and more sensitive and specific than thyroid transcription factor 1 in the differential diagnosis of primary pulmonary carcinoma: evaluation of 1674 cases by tissue microarray.

CONTEXT: Differentiation of non-small cell carcinoma into histologic types is important because of new, successful therapies that target lung adenocarcinoma (ACA). TTF-1 is a favored marker for lung ACA but has limited sensitivity and specificity. Napsin A (Nap-A) is a functional aspartic proteinase that may be an alternative marker for primary lung ACA. OBJECTIVES: To compare Nap-A versus TTF-1 in the typing of primary lung carcinoma and the differentiation of primary lung ACA from carcinomas of other sites. DESIGN: Immunohistochemistry for Nap-A and TTF-1 was performed on tissue microarrays of 1674 cases of carcinoma: 303 primary lung ACAs (18.1%), 200 primary squamous cell lung carcinomas (11.9%), 52 primary small cell carcinomas of the lung (3.1%), and carcinomas of the kidney (n  =  320; 19.1%), thyroid (n  =  96; 5.7%), biliary (n  =  89; 5.3%), bladder (n  =  47; 2.8%), breast (n  =  93; 5.6%), colon (n  =  95; 5.7%), liver (n  =  96; 5.7%), ovaries (n  =  45; 2.7%), pancreas (n  =  48; 2.9%), prostate (n  =  49; 2.9%), stomach (n  =  93; 5.6%), and uterus (n  =  48; 2.9%). Cases were evaluated against a negative control as negative, weak positive, and strong positive. RESULTS: Nap-A was more sensitive than TTF-1 for primary lung ACA (87% versus 64%; P < .001). Nap-A was more specific than TTF-1 for primary lung ACA versus all tumors, excluding kidney, independent of tumor type (P < .001). CONCLUSIONS: Nap-A is superior to TTF-1 in distinguishing primary lung ACA from other carcinomas (except kidney), particularly primary lung small cell carcinoma, and primary thyroid carcinoma. A combination of Nap-A and TTF-1 is useful in the distinction of primary lung ACA (Nap-A(+), TTF-1(+)) from primary lung squamous cell carcinoma (Nap-A(-), TTF-1(-)) and primary lung small cell carcinoma (Nap-A(-), TTF-1(+)).

Genetics and imaging of hepatocellular adenomas: 2011 update.

Hepatocellular adenomas are benign liver neoplasms with specific but varied histopathologic findings and tumor biology. The results from recent studies of the pathologic and genetic basis of hepatocellular adenomas provide important insights into the pathogenesis and molecular changes, as well as the putative oncologic pathways used by diverse adenoma subtypes. On the basis of the genetic and pathologic features, hepatocellular adenomas are categorized into three distinct subtypes: (a) inflammatory hepatocellular adenomas, (b) hepatocyte nuclear factor 1 α-mutated hepatocellular adenomas, and (c) ß-catenin-mutated hepatocellular adenomas. Different subtypes show variable clinical behavior, imaging findings, and natural history, and thus the options for treatment and surveillance may vary. Cross-sectional imaging plays an important role in the diagnosis, subtype characterization, identification of complications, and surveillance of hepatocellular adenomas. New schemas for genotype-phenotype classification of hepatic adenomas, as well as management triage of patients with specific subtypes of adenomas, are being proposed in an attempt to improve clinical outcomes.

Micropapillary carcinoma of the urinary bladder: report of a case and review of its cytologic features.

Micropapillary carcinoma (MPC) is an aggressive variant of urothelial carcinoma. MPC has a propensity to invade lymphovascular spaces and detrusor muscle early in the disease that often leads to upstaging and/or lymph node metastasis in many cases at cystectomy. Its association with the usual high-grade urothelial carcinoma provides an easy recognition of malignancy in cytology specimens without attempt at separating or identifying the MPC component. This may be related to our limited familiarity of its cytologic features with only 4 cases described in the literature. We report another case of MPC and highlight its features in cytologic preparations including the presence of singly scattered tumor cells with high nuclear to cytoplasmic ratio and pleomorphic nuclei, clustered cells devoid of fibrovascular core (micropapillae), 3-dimensional cell aggregates, cytoplasmic vacuoles, and micropapillae exhibiting some features of low-grade urothelial neoplasm. Appreciation of these features may help facilitate its early diagnosis and hopefully a better outcome for these aggressive tumors.

Comprehensive update on select immune-mediated gastroenterocolitis syndromes: implications for diagnosis and management.

There is a heterogeneous group of noninfectious gastroenterocolitis syndromes that are characterized by immune dysregulation. Recent advances in pathologic analysis have allowed for better characterization of many of these disorders. Some entities demonstrate characteristic disease distribution, epidemiologic features, natural history, and response to specific therapy. For instance, celiac disease occurs in genetically susceptible individuals who are sensitive to gluten, eosinophilic esophagitis is an immune response to ingested allergens, and microscopic colitis predominantly occurs in older patients with chronic diarrhea and is induced or exacerbated by drugs. Eosinophilic gastroenteritis has a variety of clinical and imaging manifestations. Crohn disease and ulcerative colitis are multifactorial immune-mediated chronic inflammatory disorders and have become increasingly prevalent in recent years. Multidetector computed tomography and magnetic resonance imaging provide valuable information that may be used to diagnose these conditions, guide treatment, and assess changes after treatment, and the role of imaging in evaluating response to therapy continues to evolve and expand.

Current update on borderline ovarian neoplasms.

OBJECTIVE: Borderline ovarian tumors comprise a unique group of noninvasive ovarian neoplasms with characteristic histology and variable tumor biology that typically manifest as low-stage disease in younger women with resultant excellent prognosis. CONCLUSION: Borderline tumors are considered to be precursors of low-grade ovarian cancers. Accurate diagnosis and staging facilitate optimal patient management particularly in patients desiring to preserve fertility.