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Objectives: Small sample size limits the number of immunostains that may be attempted in colorectal carcinoma (CRC) biopsy specimens. We investigated the utility of dual stain with special AT-rich sequence binding protein 2 (SATB2) or caudal-type homeobox 2 (CDX2) and cytokeratin 20 (CK20) or villin in identifying CRC., Methods: Tissue microarrays with 222 CRCs and 375 other carcinomas were built. Dual stain was performed pairing nuclear stains CDX2 or SATB2 with CK20 or villin., Results: All four single stains showed excellent sensitivity (93%-99%) but variable specificity (56%-88%) for CRC. All four dual stains also showed excellent sensitivity (90%-96%) while much improved specificity (88%-98%) compared with single stains. SATB2 dual stain (with CK20 or villin) showed a higher specificity than CDX2 dual stain (with CK20 or villin) with a comparable sensitivity., Conclusions: SATB2 dual stain shows the greatest potential clinical utility in identifying CRC and is superior to CDX2 dual stain. More important, SATB2 dual stain could be helpful for specimens with limited tissues or those having a nonclassic staining pattern.

Objectives: Determination of the primary site of origin for mucinous neoplasms identified in the peritoneal and/or pelvic cavities may be challenging, with major differential diagnoses including appendiceal mucinous neoplasm (AMN) and ovarian mucinous neoplasm (OMN). Special AT-rich sequence binding protein 2 (SATB2) has been shown to be highly selectively expressed in the lower gastrointestinal tract, including the appendix., Methods: We investigated the utility of a dual stain (DS) with SATB2 or caudal type homeobox 2 (CDX2) and cytokeratin 20 (CK20) or villin in distinguishing AMNs from OMNs. Tissue microarrays with 40 AMNs and 18 OMNs were stained with SATB2 or CDX2 paired with either CK20 or villin., Results: SATB2 single stain showed a good sensitivity of 83% and the highest specificity of 78% for AMNs over OMNs among all four stains. DS with SATB2 and villin showed an identical sensitivity of 78% but specificity increased to 94%, while DS with SATB2 and CK20 showed a sensitivity of 80% and a specificity of 100%. In contrast, DS with CDX2 and CK20/villin showed slightly higher sensitivity but much lower specificity., Conclusions: DS with SATB2/CK20 shows the greatest potential clinical utility in distinguishing AMNs from OMNs and is superior to DS with CDX2/CK20. Importantly, DS could be helpful for specimens with limited tissues., (© American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

In immunocompromised patients, oral ulcerations are common and have a wide spectrum of causes, including herpesvirus infection. We report on a case in which an oral ulcer was simultaneously infected by herpes simplex (HSV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) in a kidney-pancreas transplant recipient. A 46-year-old woman presented with a clinically nonspecific dorsal tongue ulcer of 3 months duration. Histopathologic evaluation indicated keratinocytes exhibiting herpetic viral cytopathic effect. Nuclear and cytologic alterations suggestive of CMV infection were found in endothelial cells subjacent to the ulcer. Immunohistochemistry testing for HSV and CMV was positive in these cells. Large atypical mononuclear cells were also evident in the ulcer bed's inflammatory infiltrate, which had intense nuclear positivity for Epstein-Barr encoding region in situ hybridization. We believe this is the first well-documented report of the definitive concomitant presence of HSV, CMV, and EBV in an immunocompromised patient. Although the pathogenesis of coinfected ulcers remains unknown, a synergistic effect is possible., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: Somatic BRAF mutation in colon cancer essentially excludes Lynch syndrome. We compared BRAF V600E immunohistochemistry (IHC) with BRAF mutation in core, biopsy, and whole-section slides to determine whether IHC is similar and to assess the cost-benefit of IHC., Methods: Resection cases (2009-2013) with absent MLH1 and PMS2 and prior BRAF mutation polymerase chain reaction results were chosen (n = 57). To mimic biopsy specimens, tissue microarrays (TMAs) were constructed. In addition, available biopsies performed prior to the resection were available in 15 cases. BRAF V600E IHC was performed and graded on TMAs, available biopsy specimens, and whole-section slides. Mutation status was compared with IHC, and cost-benefit analysis was performed., Results: BRAF V600E IHC was similar in TMAs, biopsy specimens, and whole-section slides, with only four (7%) showing discordance between IHC and mutation status. Using BRAF V600E IHC in our Lynch syndrome screening algorithm, we found a 10% cost savings compared with mutational analysis., Conclusions: BRAF V600E IHC was concordant between TMAs, biopsy specimens, and whole-section slides, suggesting biopsy specimens are as useful as whole sections. IHC remained cost beneficial compared with mutational analysis, even though more patients needed additional molecular testing to exclude Lynch syndrome., (Copyright© by the American Society for Clinical Pathology.)

For primary bladder tumors, distinguishing urothelial carcinoma (UC) invading the fibromuscular stroma of the prostate (pT4a) from in situ UC involving prostatic ducts can be difficult. Immunohistochemical markers (cytokeratin [CK]5/6, CK5, CK7, CK20, p53, p63, high-molecular-weight keratin [HMWK], androgen receptor, prostate-specific antigen [PSA], prostate specific acid phosphatase [PSAP], laminin, CD44s, CD141) were assessed for their usefulness in determining depth of UC invasion in the prostate. In cystoprostatectomy specimens containing in situ UC in prostatic ducts, both CK5/6 and CK5 clearly differentiated prostatic basal cells from in situ UC. The remaining markers were not effective in determining depth of tumor invasion. Double-stain combinations CK7/CK5 and p53/CK5 were performed and robustly color contrasted in situ tumor from surrounding basal cells. The use of CK5/6, CK5, CK7/CK5, or p53/CK5 is recommended to assist in determining the depth of UC invasion in the prostate when histologic findings are equivocal.

DOG1, a transmembrane calcium-regulated chloride channel protein, is a sensitive and specific marker for gastrointestinal stromal tumors compared with other spindle cell and epithelioid neoplasms. Overexpression has also been described in a variety of both benign and malignant epithelial neoplasms. Recently, DOG1 immunoreactivity has been reported in pancreatic solid pseudopapillary tumors (SPT), suggesting a role as a marker for SPT. Utilizing immunohistochemistry, we evaluated DOG1 expression in pancreatic neoplasms to determine the prevalence of staining and establish diagnostic utility. Multiple tissue microarrays (TMA) were created from cores of formalin-fixed paraffin-embedded blocks containing pancreatic adenocarcinomas (n=112), neuroendocrine tumors (n=99), serous cystadenomas (n=28), and SPT (n=14) as well as normal pancreas (n=12). Immunoreactivity for DOG1 (clone K9) was assessed for intensity (1 to 3+), percentage of tumor positivity and location. Of the 99 cases of neuroendocrine tumors, only 2 (2%) were focally positive. Patchy staining was identified in 8 cases (7%) of adenocarcinoma of 1 to 2+ intensity, involving 15% to 80% of the tumor cells and primarily seen in a membranous and luminal distribution. In contrast to a previous report, no DOG1 positivity was observed in SPT, evaluated by both TMA and full sections. The TMAs of serous cystadenomas and normal pancreas were negative for DOG1. Rarely, pancreatic islets displayed granular, cytoplasmic staining. DOG1 antibody clone K9 is not a useful marker for SPT or other primary pancreatic neoplasms. Additional studies may be helpful to evaluate differences between clones of DOG1.

We performed a histologic and immunohistochemical assessment of 53 noninvasive appendiceal epithelial proliferations, appropriating terminology and using markers shown useful in differentiating serrated colorectal polyps. These were classified as hyperplastic polyp (HP), sessile serrated adenoma (SSA), mixed serrated and adenomatous lesion (MSAL), mucinous cystadenoma (MCA), or conventional adenoma (CAD). Immunohistochemical analysis for cytokeratin (CK) 20, Ki-67, MUC6, and beta-catenin was performed. Diagnoses were as follows: HP, 6; SSA, 12; HP vs SSA, 3; MSAL, 16; MCA, 14; and CAD, 2. All HPs showed expanded (beyond surface) CK20 and expanded or normal (base) Ki-67; 1 was MUC6+. Most SSAs and MSALs were CK20-expanded or expanded with random expression in deep crypts (Ex/I) and Ki-67-expanded, Ex/I (expanded with asymmetry), or normal. All SSAs and 8 of 16 MSALs were MUC6+. CADs were CK20-Ex/I, Ki-67-Ex, and MUC6-; 1 showed nuclear beta-catenin expression. Serrated appendiceal lesions can be categorized using colorectal terminology. MUC6 is associated with SSA morphologic features. Similar immunohistochemical patterns in SSA and MSAL suggest a link between these lesions.

The diagnosis of serous microcystic adenoma (SMA) is usually straightforward. For small biopsies and/or unusual variants, the differential diagnosis includes other pancreatic or metastatic neoplasms showing cystic or clear cell features. We evaluated immunostains for potential use in the diagnosis of SMA. Cases of SMA were identified from archival files. Tissue cores (2 per block) were arrayed to create a microarray of cores measuring 2mm each. Additionally, microarrays previously constructed from 56 pancreatic adenocarcinomas (PACs) and 64 pancreatic endocrine tumors (PENs) were studied. The microarrays were stained with calponin, chromogranin, CD10, alpha-inhibin, and monoclonal neuron-specific enolase (m-NSE). Subsequently, some were stained with MUC6, melan-A, D2-40, h-caldesmon, smooth muscle actin, and smooth muscle myosin. For SMAs, staining was seen with calponin (85.2%), alpha-inhibin (96.2%), and m-NSE (96.2%). Focal weak staining was seen with MUC6 (65%). All SMAs were negative with chromogranin, CD10, melan-A, D2-40, h-caldesmon, smooth muscle actin, and smooth muscle myosin. In contrast, calponin was negative in all PACs and PENs. Staining for alpha-inhibin was absent in PACs and present in 4.1% of PENs; whereas immunoreactivity for m-NSE was present in 26.8% of PACs and 73.7% of PENs. Chromogranin staining was present in 9.1% of PACs and 100% of PENs. An immunohistochemical profile of staining with calponin, alpha-inhibin, and m-NSE and absent staining with chromogranin supports the diagnosis of SMA, and distinguishes SMA from PAC and PEN. Calponin and alpha-inhibin are the most useful positive markers for SMA, and are negative in most entities in the differential diagnosis.

Aim: To report the clinicopathological features of patients with serous cystadenomas of the pancreas., Methods: Thirty-three cases of serous cystadenoma diagnosed between 1977 and 2006 were retrieved from the files of the Ohio State University Medical Center. Clinical data and microscopic slides were reviewed., Results: The patients included 27 women and 6 men with an age range of 38-83 (mean 64.3) years. The clinical presentation included 13 patients with abdominal pain and 8 patients with abdominal mass; 9 tumors were found incidentally. Abdominal CT scans in 25 patients were interpreted as suspicious for carcinoma in 8 (32%), suspicious for serous cystadenoma in 8, neoplasm not otherwise specified in 8, and suspicious for a pseudocyst in 1. Only 7 patients underwent a preoperative biopsy, and 5 of these were diagnosed as having a serous cystadenoma. All but 2 of the patients underwent surgical resection of the tumor. The serous cystadenomas varied in size from 1.0 to up to 13 cm in maximum dimension, and all but one had a multicystic appearance. Of the 33 serous cystadenomas, 20 (61%) were located in the pancreatic tail, 4 (12%) in the pancreatic body, 4 in the pancreatic body and tail, and 5 (15%) in the head of the pancreas. Follow-up in 17 patients (median 3 years, range from 1 month to 11 years) showed no recurrence of serous cystadenomas. One patient had von Hippel-Lindau syndrome, 4 patients had diabetes mellitus, 3 patients had metastatic cancer, and 2 patients had ovarian tumors., Conclusions: Serous cystadenoma is an uncommon neoplasm that can be confused with malignancy both clinically and radiologically; a correct diagnosis is important in order to provide an accurate prognosis., (Copyright 2008 S. Karger AG, Basel.)

Background: Anaplastic large cell lymphoma (ALCL) (Ki-1/CD-30 positive) is an uncommon lymphoproliferative disorder that may be of T cell or null cell type. ALCL has been reported in fine needle aspirations of lymph nodes and pleural or peritoneal fluid cytology. In human immunodeficiency virus (HIV)-positive patients, ALCL appears to be more common and run a more aggressive course., Case: A 39-year-old black man, seropositive for HIV, presented with acute renal failure secondary to bilateral ureteral obstruction by a pelvic mass involving the urinary bladder. Bladder wash cytology and subsequent biopsy of the mass were diagnostic of ALCL. The ALCL was CD30+ and null cell type, with negative CD2, CD3, CD4, CD5, CD7, CD8, CD20, CD45, CD79a, ALK-1, granzyme B, cytokeratin (AE1/AE3), placental alkaline phosphatase (PLAP) and S-100. The patient expired 9 months after the diagnosis, despite aggressive therapy., Conclusion: This is a rare occurrence of ALCL (CD 30 positive, null cell type) in the urinary bladder in an HIV+ patient. Presumptive diagnosis was made by bladder wash cytology and subsequently confirmed by biopsy. Urinary cytologic examination is a useful diagnostic tool. In HIV+/immunosuppressed patients with urinary symptoms and an obstructive mass, ALCL should be considered in the differential diagnosis.

Mucin expression patterns have been studied in tumors from various sites. Previous studies have shown an association of MUC1 with poor prognosis and MUC2 and MUC5AC with a mucinous phenotype. The pattern of mucin expression in endometrial carcinomas has not been documented in a large series. We determined the mucin expression profile in endometrial carcinomas and evaluated the relationship between mucin expression and clinical-pathologic parameters. A tissue microarray of 310 cases of endometrial carcinoma with known clinical outcome was constructed from formalin-fixed, paraffin-embedded donor blocks using two 0.6 mm cores from each tumor. Sections were stained with monoclonal antibodies against MUC1, MUC2, MUC4, MUC5AC, and MUC6. Staining was considered positive if greater than or equal to 5% of cells stained positively in either core. Mucin expression was correlated with tumor type, histologic grade, International Federation Gynecology and Obstetrics stage, lymph node involvement, depth of myometrial invasion, patient age, ethnicity, and clinical outcome. MUC1 was expressed in 267/310 (86.1%) of endometrial carcinomas, MUC2 in 2/310 (0.6%), MUC4 in 73/310 (23.5%), MUC5AC in 1/310 (0.3%), and MUC6 in 4/310 (1.2%). Endometrioid endometrial carcinoma showed a higher rate of MUC1 expression than nonendometrioid endometrial carcinoma (227/258, 88.0% vs. 39/52, 75.0%, P=0.01). No significant differences in any of the mucins were noted among the other end points evaluated. Mucin expression did not correlate with tumor grade, stage, or patient outcome.

Many patients with pancreatic carcinoma have stent placement for biliary obstruction before resection. Stent-associated atypia, found in common bile duct (CBD) margins at the time of resection, may be confused with malignancy. We evaluated histologic and immunohistochemical changes in CBD margins from resection specimens for pancreatic carcinoma. Histologic findings in CBDs, including ulcer and inflammation; epithelial metaplasia, atypia, and gland complexity; and increased wall thickness, nerve entrapment, and smooth muscle content, were compared in 30 stented and 31 nonstented CBD margins from pancreaticoduodenectomies for carcinoma and 13 normal CBDs from autopsy material. The proliferation index was calculated for stented and nonstented CBDs after Ki-67 immunohistochemical staining. Immunostaining for Ki-67, p53, and c-erbB-2 was performed in stented CBDs and corresponding carcinomas. All the histologic changes occurred more frequently in stented and nonstented CBD margins from carcinoma patients than in normal CBDs. Stented CBDs had significantly increased epithelial changes and Ki-67 proliferation rate as compared with nonstented CBDs. The stented CBDs had significantly less p53 and c-erbB-2 expression as compared with corresponding pancreatic carcinomas. Caution should be applied when interpreting atypia in CBD margins from patients with a history of CBD stenting. Changes found in stented CBDs are characteristic, and in most cases can be distinguished from malignancy. In difficult cases, immunohistochemistry may be useful.

Background: Fibromatosis or desmoid tumor is a rare soft tissue tumor that lacks a metastatic potential, but is characterized by a locally aggressive and infiltrating growth pattern and a high propensity toward local recurrence if incompletely excised., Case Presentation: We report a patient with three post-surgical recurrences of fibromatosis of the breast over a seven year period. The fibromatosis was found to be involving the chest wall musculature and causing persistent and worsening pain. An aggressive operative strategy was undertaken, consisting of mastectomy with en bloc resection of the underlying chest wall musculature, ribs, and parietal pleura., Conclusion: Aggressive surgical management of fibromatosis of the breast with suspected chest wall involvement is appropriate to attempt to obtain a long-term durable cure.

Duodenal gangliocytic paraganglioma is a rare tumor that characteristically occurs in the second portion of the duodenum and typically presents with gastrointestinal bleeding. Gangliocytic paragangliomas have a characteristic triphasic microscopic appearance with epithelioid cells, spindle cells, and ganglion cells, resulting in a complex histology with features of paraganglioma, carcinoid, and ganglioneuroma. Duodenal gangliocytic paragangliomas have an excellent prognosis after surgical resection but metastatic spread to regional lymph nodes and recurrence may rarely occur. We report a case of duodenal gangliocytic paraganglioma and discuss the radiological and pathological differential diagnosis of this rare entity.

Sclerosing perineurioma is a recently described rare benign nerve sheath tumor. The cytopathology of this neoplasm has, to our knowledge, not previously been described. We report the fine needle aspiration cytopathology of sclerosing perineurioma, discuss potential pitfalls in cytologic interpretation, and compare the aspirate with the corresponding resection specimen.

Cat-scratch disease of the breast has been previously reported. This report describes a very unusual case of cat-scratch disease of the breast caused by Bartonella quintana in which the clinical and radiographic presentation mimicked that of inflammatory breast cancer.

Reduction mammaplasty (RM) is a common surgical procedure that yields a variable amount of tissue for pathologic examination. Occult breast carcinomas are detected rarely in these specimens. We evaluated the pathologic findings in RM specimens performed in our institution during an 11.5-year period (July 1989 to December 2000). A total of 560 patients who had undergone RM were identified, 503 bilateral and 57 unilateral. The average number of blocks submitted per breast was 3.9 (range, 1-23). Pathologic changes were present in 338 cases (60.4%). Unsuspected carcinomas (small invasive carcinomas, 3; ductal carcinoma in situ, 1) were found in 4 cases (0.7%). Atypical ductal and/or atypical lobular hyperplasia were identified in 8 cases (1.4%). Lesions associated with a mildly increased carcinoma risk (moderate/florid ductal hyperplasia, sclerosing adenosis, and papilloma) were identified in 52 cases (9.3%). Other findings included fibrocystic changes, fibrosis, mild ductal hyperplasia, fibroadenoma, and adenosis. Pathologic examination of RM specimens provides important clinical information and should be performed routinely.

Hyperforin is currently considered to be the major active antidepressant constituent of the medicinal herb St. John's wort (Hypericum perforatum L.). The mechanism of action however, is still largely unknown, although the involvement of sodium and calcium has been recently inferred. In the present study hyperforin (5 microM) significantly potentiated the release of endogenous aspartate and glutamate from mouse cortical slices when stimulated by veratridine or potassium. Hyperforin (5 microM) also stimulated the release of aspartate, glutamate, serine, glycine and GABA when perfused on its own. Perfusion of the sodium channel blocker, tetrodotoxin (TTX) inhibited the effect of hyperforin, whereas removal of extracellular calcium potentiated the effect. Our observations suggests that hyperforin increases the overflow of neurotransmitters from mouse cerebral cortex possibly through facilitating the entry of sodium into the neurone which leads to the release of calcium from intracellular stores.