Muscularis propria detected at colonic biopsy is not a critical value.

Perforation is a rare but potentially serious complication of cold forceps colonic biopsies. The presence of muscularis propria might portend increased risk of perforation and warrant urgent communication with endoscopists. However, identifying muscularis propria at time of biopsy is difficult for many reasons, including histologic overlap with muscularis mucosa. Incidental muscularis propria obtained in this manner has yet to be studied. Our objectives were to characterize the morphology of muscularis propria obtained incidentally via cold forceps colonic biopsies, establish practical criteria for diagnosing muscularis propria, and determine whether diagnosing muscularis propria correlates with perforation clinically. We retrospectively reviewed 3 specimens from nontargeted cold forceps colonic biopsies for which pieces of muscularis propria were presumed to be visualized based on larger size or lower nuclear density compared to the corresponding muscularis mucosa. These specimens were then compared to normal transmural control tissue from colectomy to confirm whether nuclear density or other features could distinguish muscularis propria from muscularis mucosa. Muscularis propria in the control tissue had lower nuclear density, smoother cytoplasmic texture, and more cytoplasmic pallor compared to the muscularis mucosa in the control tissue. This constellation of features was seen in all 3 specimens obtained via biopsy and therefore confirmed the presence of muscularis propria, though all patients lacked perforation clinically. Large size, low nuclear density, smooth cytoplasm, and pale cytoplasm identify objects as muscularis propria at time of colonic biopsy. The presence of muscularis propria fails to correlate with perforation clinically and does not warrant urgent communication.

Incidental Hepatic Tissue Obtained via Routine Cholecystectomy.

Background. The hepatic tissue that may occupy specimens from routine cholecystectomies has yet to be studied. Our objectives were to determine the prevalence of hepatic tissue obtained at routine cholecystectomy, to determine whether such hepatic tissue can histologically withstand technical artifacts commonly associated with cholecystectomy, and to determine whether examining such hepatic tissue has diagnostic utility. Materials and Methods. We retrospectively reviewed 50 specimens from routine cholecystectomies that were performed by surgeons who lacked knowledge of our study. All 50 specimens were grossed according to standard protocol, with only limited, nontargeted sampling of the rough nonperitonealized margin, and were received without fixative. Results. Twelve specimens (24.0%) contained hepatic tissue. The hepatic tissue measured up to 44.5-mm long and 1.8-mm wide and contained up to 11 complete portal tracts. Hepatic tissue in 3 specimens satisfied criteria for adequacy established for core biopsies based on number of portal tracts or size. Despite cautery and delayed fixation, all hepatic tissue had surprisingly well-preserved histology. Pathologic findings included nonalcoholic fatty liver disease, von Meyenburg complex, chronic cholestasis, and senescence. Conclusions. The hepatic tissue that accompanies specimens from routine cholecystectomies may be relatively common, can be large, is well preserved, and can harbor diagnostically useful information.

Phenotypic and genotypic differences in colorectal carcinoma among Caucasians, Asians, and Hispanics lack statistical significance.

Colorectal carcinoma (CRC) has been shown to have both genetic and environmental factors that can promote carcinoma development. Previous studies have found ethnic differences in the distribution of molecular phenotypes of CRC. Very little specific data exist regarding Hispanic CRC, and these data primarily focus on epidemiology or location of carcinoma. Our retrospective study analyzed 562 Caucasian, Asian, and Hispanic CRC patients at the UCI Medical Center from 2004 to 2012. The results showed that there were no statistically significant differences with respect to mean age, gender or site of carcinoma among the three ethnic groups. There were no statistically significant differences among the three ethnicities with respect to rates of MSI, mutated BRAF, and mutated KRAS. The Caucasian group had a non-significant higher rate of MSI (15%) and BRAF mutation (12%) than the Asian and Hispanic groups. Hispanics had a non-significant higher rate of KRAS mutation (59%) than Caucasians (38%) and Asians (37%). The results of this study demonstrated a higher rate of MSI and BRAF mutation in the Caucasian group and a higher rate of KRAS mutation in the Hispanic group, however differences were not statistically significant.

Massive Submucosal Ganglia in Colonic Inertia.

CONTEXT: - Colonic inertia is a debilitating form of primary chronic constipation with unknown etiology and diagnostic criteria, often requiring pancolectomy. We have occasionally observed massively enlarged submucosal ganglia containing at least 20 perikarya, in addition to previously described giant ganglia with greater than 8 perikarya, in cases of colonic inertia. These massively enlarged ganglia have yet to be formally recognized. OBJECTIVE: - To determine whether such "massive submucosal ganglia," defined as ganglia harboring at least 20 perikarya, characterize colonic inertia. DESIGN: - We retrospectively reviewed specimens from colectomies of patients with colonic inertia and compared the prevalence of massive submucosal ganglia occurring in this setting to the prevalence of massive submucosal ganglia occurring in a set of control specimens from patients lacking chronic constipation. RESULTS: - Seven of 8 specimens affected by colonic inertia harbored 1 to 4 massive ganglia, for a total of 11 massive ganglia. One specimen lacked massive ganglia but had limited sampling and nearly massive ganglia. Massive ganglia occupied both superficial and deep submucosal plexus. The patient with 4 massive ganglia also had 1 mitotically active giant ganglion. Only 1 massive ganglion occupied the entire set of 10 specimens from patients lacking chronic constipation. CONCLUSIONS: - We performed the first, albeit distinctly small, study of massive submucosal ganglia and showed that massive ganglia may be linked to colonic inertia. Further, larger studies are necessary to determine whether massive ganglia are pathogenetic or secondary phenomena, and whether massive ganglia or mitotically active ganglia distinguish colonic inertia from other types of chronic constipation.

Specimens from biopsies of colorectal polyps often harbor additional diagnoses.

Objectives. The utility of examining specimens from colorectal biopsies of polyps for nonneoplastic diseases is currently unknown. Our objectives were to characterize such additional diagnoses that could be rendered. Methods. We retrospectively and prospectively reviewed specimens from endoscopic biopsies of colorectal polyps obtained during routine screening or surveillance. Results. 17 of 168 specimens (10.1%) contained additional diagnoses, including schistosomiasis, eosinophilic colitis, intestinal spirochetosis, melanosis coli, and other entities. These findings were easily overlooked because they often affected mucosa that was spared by the polyps or were often evident only at high magnification. Schistosomiasis, eosinophilic colitis, and intestinal spirochetosis were clinically occult. Conclusions. Specimens from biopsies of colorectal polyps often harbor other diagnoses, in addition to polyps, and can be simultaneously screened for polyps and examined for nonneoplastic diseases. Detection of other diagnoses in addition to polyps requires awareness, examination at high magnification, and examination of areas spared by the polyps.

Colorectal stents orient specimens and induce artifacts that mimic Crohn disease.

Colorectal malignancies may be stented to alleviate obstruction. The stent is a polarized and braided network of metallic wires. Pathology associated with colorectal stents is yet to be described. The authors reviewed 7 cases involving stented colorectal segments from patients lacking clinical suspicion of Crohn disease. In 4 cases, orientation of the specimens and stents matched the corresponding anatomic landmarks. In 3 cases, the specimens lacked helpful anatomic landmarks, and orientation was possible only after correlating with the intrinsic polarity of the stents. Stented areas showed artifacts resembling Crohn disease, including rounded cobblestones, pseudopolyps, and simple fissures, as well as unique artifacts including rhomboid cobblestones, complex fissures, oblique fissures with remarkably straight edges, and conical fragments of tissue that appeared to float. Crohn disease was misdiagnosed in 1 case in which the stent was removed intraoperatively and was never received. Colorectal stents help orient ambiguous specimens and induce patterned injury that can be confused with Crohn disease.

Immunohistochemical basis for adjuvant anti-angiogenic targeted therapy for renal carcinoid: initial case report.

OBJECTIVES: To evaluate the immunohistochemical profile of a carcinoid (low grade neuroendocrine tumor of the kidney) from a patient with lymph node positive disease who remains disease free for 31 months after radical nephrectomy, lymph node dissection, and adjuvant therapy with sunitinib malate. METHODS: Immunohistochemical staining was performed for chromogranin, synaptophysin, CD31, VEGF, HIF-1α, HIF-2, and Glut-1. Staining was evaluated in 3 high-power fields and samples scored as strongly positive (3+), moderately positive (2+), weakly positive (1+), or negative (0). A clear cell renal cell carcinoma was used as positive control. RESULTS: Immunohistochemical staining was strongly positive VEGF, weak to moderately positive for HIF-2, and negative for HIF-1α and Glut-1. CONCLUSIONS: Our case of primary renal carcinoid stained intensely for VEGF and HIF-2, consistent with a VHL-HIF1-HIF2-Glut1 independent pathway for VEGF activation. These data suggest that like other neuroendocrine tumors, primary renal carcinoid is a potential target for anti-angiogenic therapy with sunitinib.

Comprehensive evaluation of colorectal polyps in specimens from endoscopic biopsies.

Modern evaluation of specimens from biopsies of colorectal polyps has become increasingly complex because of tremendous progress in the understanding of colorectal neoplasia. Although pathologists are generally familiar with the basic handling of carcinoma in the setting of polypectomies or resections, the comprehensive evaluation of specimens from biopsies of colorectal polyps obtained with forceps is far from intuitive and has yet to be reviewed. Comprehensive evaluation requires always addressing several key issues, even when dealing with seemingly routine cases. These issues include taking further action when initial sections lack polyps, accurately quantitating polyps, accurately classifying polyps, determining whether thresholds are met for considering conditions at high risk for carcinoma, detecting incidental findings other than polyps, and determining which incidental findings are clinically significant. In particular, polyposis with attenuated phenotype or Lynch syndrome may be clinically occult, and the possibility of these entities should always be kept in mind, regardless of age or history. Ancillary studies performed immediately on carcinoma that is detected at biopsy guides surgery, guides medical therapy, prognosticates, provides evidence for hereditary neoplasia, and guides surveillant colonoscopy for the family.

Pseudolipomatosis affects specimens from endometrial biopsies.

Pseudolipomatosis refers to optically clear vacuoles that artifactually contaminate specimens, and it most commonly affects the gastrointestinal tract. Pseudolipomatosis closely resembles adult white fat and is of group "A" or "B" when vacuoles have mild or marked variation in size, respectively. Pseudolipomatosis has yet to be reported to occur in the endometrium. Pseudolipomatosis in the endometrium might be easily mistaken for extrauterine adipocytes and misdiagnosed as perforation. We retrospectively reviewed 50 consecutive specimens from endometrial biopsies to determine the prevalence of endometrial pseudolipomatosis and whether pseudolipomatosis was related to perforation. All 50 specimens contained pseudolipomatosis of group "B," and lacked extrauterine tissue. To our knowledge, all patients lacked clinical evidence of perforation at follow-up. Pseudolipomatosis commonly affects specimens from endometrial biopsies and is likely unrelated to perforation. Awareness of pseudolipomatosis is necessary to avoid misdiagnosing uterine perforation.

Docetaxel-induced mitotic arrest in epithelium of gallbladder: a hitherto unreported occurrence.

Chemotherapeutic agents that bind tubulin cause mitotic arrest, which may be seen histologically. Such mitotic arrest has been reported to occur in the skin, alimentary canal, lungs, liver, bone marrow, endometrium, breasts, or in ascites following treatment with paclitaxel, vincristine, colchicine, podophyllotoxin, or maytansine. Mitotic arrest as a result of docetaxel, a taxane that binds tubulin, has yet to be reported. Mitotic arrest in the gallbladder has also yet to be reported. We recently encountered a case of dramatic mitotic arrest as a result of docetaxel, involving the gallbladder of a 66-year-old man with metastatic bronchogenic carcinoma. Strikingly abundant bizarre mitoses initially prompted a diagnosis of primary carcinoma. Carcinoma was eventually excluded based on the absence of dysplasia in all cells at interphase and the history of recent administration of docetaxel. This is the first case of mitotic arrest involving docetaxel or the gallbladder. Awareness of this phenomenon is necessary to avoid misdiagnosing carcinoma.

Iatrogenic pulse granuloma detected at prostatectomy.

Pulse granulomas are peculiar reactions to vegetable matter characterized by aggregates of hyaline rings and may be oral or extraoral. Pulse granulomas are important to recognize because they may indicate serious pathologic processes, may simulate neoplasia clinically, and may morphologically be confused with hyaline vasculopathy. We recently encountered a case involving a highly unusual pulse granuloma in a 55-year-old man who underwent prostatectomy for adenocarcinoma. Prior pancolonoscopy and digital rectal examination excluded significant colorectal disease. Microscopy showed a prominent pulse granuloma with demonstrable vegetable matter occupying periprostatic soft tissue. Interestingly, retrospective review of material from prior prostatic core biopsies revealed vegetable matter that appeared identical to the vegetable matter in the pulse granuloma. We conclude that the biopsies transrectally displaced vegetable matter, which provided the nidus for the pulse granuloma. We present the first pulse granuloma to be caused by a biopsy or to occupy periprostatic soft tissue.

Solitary fibrous tumor of the larynx.

BACKGROUND: True mesenchymal, non-cartilaginous neoplasms of the larynx are rare. Extrapleural solitary fibrous tumor (SFT) is a localized neoplasm characterized by proliferation of thin-walled vessels and collagen-producing cells and is considered within the "hemangiopericytoma-solitary fibrous tumor" spectrum. SFT primary in the larynx is exceptional. DESIGN: Case report set in a comparison with other cases reported in the English literature (MEDLINE 1966 to 2007). RESULTS: A 49-year old white male presented with difficulty breathing, progressive over the past 2 years. He denied dysphagia and weight loss. Past medical history was significant for asthma. He denied cigarette smoking or alcohol abuse. There were no cervical deformities on physical exam. Fiberoptic laryngoscopy was performed upon stabilization of respiratory function. A smooth, round, submucosal mass measuring 2.3 cm in greatest diameter arising from the inferior surface of left true vocal cord was causing near total obstruction of the endolaryngeal space. The mass was excised. The surface mucosa was intact and unremarkable. A cellular, spindle cell neoplasm was arranged in loose fascicles, associated with heavy collagen fiber deposition. The collagen was wiry and heavy. Cells were bland with cytoplasmic extensions. The nuclei were vesicular to hyperchromatic and elongated with inconspicuous nucleoli. Vessels were prominent and delicate, with patulous spaces. Mitotic figures were easily identified, but atypical forms were not present. The cells were strongly and diffusely immunoreactive with CD34 and bcl-2, while non-reactive with cytokeratin, EMA, actin, ALK-1, S100, desmin, and CD117. These findings confirmed a diagnosis of extraplural solitary fibrous tumor. Without further disease, the patient is alive without evidence of disease, 12 months after surgery. CONCLUSIONS: The characteristic histologic pattern of solitary fibrous tumor can be noted in extrapulmonary locations. Development in the larynx is uncommon, but the tumor presents as a polypoid mass with characteristic histologic and immunophenotypic features. Conservative local excision is the treatment of choice to yield an excellent prognosis.

Endoscopic ultrasound-guided fine-needle aspiration of undifferentiated carcinoma with osteoclast-like giant cells of the pancreas: a report of 2 cases with literature review.

Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas is rare. Histologically it mimics the giant cell tumor of the bone and may be associated with a ductal adenocarcinoma. We recently encountered two such cases, both of which were biopsied by EUS-guided FNA. Abundant multinucleated osteoclast-like giant cells and many uniform mononuclear cells were present in case 1 so that the diagnosis was made. In case 2, many mononuclear tumor cells with vacuolated and basophilic cytoplasm were present, and rare osteoclast-like giant cells were seen. A diagnosis of adenocarcinoma was made. In both cases, no conspicuous nuclear pleomorphism was noted in the mononuclear cells or the multinucleated giant cells. The histology of case 2 revealed a pure undifferentiated carcinoma with osteoclast-like giant cells. In addition, a liver biopsy revealed globular amyloidosis. To our knowledge, this is the first report of pancreatic undifferentiated carcinoma with osteoclast-like giant cells sampled by EUS-guided FNA and the first case of hepatic globular amyloidosis associated with this tumor.

Incidental rectal mucosa obtained via transrectal ultrasound-guided prostatic core biopsies.

A retrospective review was conducted of material from 782 transrectal ultrasound-guided prostatic core biopsies to determine whether incidental pieces of rectal mucosa obtained in this manner could harbor clinically significant rectal pathology or incur artifacts that cause diagnostic difficulty. Material from 114 biopsies (14.6%) showed rectal mucosa, and material from 19 (16.7%) showed rectal pathology, including a hyper-plastic polyp in 1, changes consistent with ulcerative proctitis in 8, focal active proctitis in 7, and granulomas in 3. The original pathologist overlooked the hyperplastic polyp. In 1 specimen, rectal lymphocytes and plasma cells that were displaced over prostatic tissue closely mimicked prostatic adenocarcinoma (Gleason score 5). Conversely, in another specimen, prostatic adenocarcinoma (Gleason score 5) that was displaced near rectal mucosa closely mimicked a rectal lymphoid aggregate. Incidental rectal mucosa obtained via transrectal ultrasound-guided prostatic core biopsies occasionally harbors clinically significant rectal pathology and rarely incurs artifacts that cause diagnostic difficulty.

Intramucosal ganglion cells in normal adult colorectal mucosa.

Intramucosal ganglion cells are incompletely understood. Reviewed were 100 normal specimens from colorectal biopsies of nonconstipated adults to firmly establish the existence of intramucosal ganglion cells in normal adult colorectal mucosa, determine whether intramucosal giant ganglia exist, and compare the prevalence of colorectal intramucosal ganglion cells between men and women. Fifty specimens from each gender were examined. Twenty specimens contained intramucosal ganglion cells, including 15 from women (75%) and only 5 from men (25%). Intramucosal ganglion cells occurred singly or in clusters. One woman had large disciform and globular clusters with 7 ganglion cells, resembling giant ganglia. Awareness of ganglion cells and large ganglia in normal mucosa is necessary to avoid potential confusion with ectopic ganglion cells and submucosal giant ganglia seen in adult intestinal neuronal dysplasia. Intramucosal ganglion cells in normal colorectal mucosa are particularly common in women. This disparity might contribute to colorectal neurophysiologic differences between genders.

Pulse granulomas detected in gallbladder, fallopian tube, and skin.

CONTEXT: Foreign material typically elicits reactions dominated by multinucleated giant cells. Pulse granulomas are peculiar reactions to particles of food that are characterized by clusters of small to medium-sized hyaline rings. Pulse granulomas are rare and have occupied only the lungs, in association with aspiration, and the alimentary canal, in association with oral pathology, colonic diverticula, and a rectal mass. OBJECTIVE: To report pulse granulomas that occupied previously unrecognized sites and to alert pathologists to the diagnostic pitfall of mistaking pulse granulomas for other entities. DESIGN: We retrospectively reviewed 3 recently encountered cases that involved pulse granulomas in the gallbladder, fallopian tube, and skin. RESULTS: In all cases, pulse granulomas were associated with fistulae involving the gastrointestinal tract. One fistula was clinically occult. Microscopy showed barium-laden histiocytes admixed with hyaline rings, with or without vegetable matter, confirming fistulae involving the gastrointestinal tract. Absence of other features of chronicity, including sarcoid-type granulomas and Langhans-type giant cells, helped to essentially exclude Crohn disease. In 1 case, hyaline rings of pulse granulomas closely resembled hyaline vasculopathy of amyloidosis, diabetes, or hypertension. Surprisingly, polariscopy failed to detect any vegetable matter. In 1 case, negative polariscopy contributed to the difficulty in finding rare vegetable matter. CONCLUSIONS: We demonstrated that pulse granulomas can occur outside the lungs and alimentary canal, and can be associated with fistulae involving the gastrointestinal tract. Awareness of this finding is necessary to avoid confusion with Crohn disease and hyaline vasculopathy. Polariscopy may fail to detect vegetable matter.

Automated virtual microscopy of gastric biopsies.

BACKGROUND: Automated virtual microscopy of specimens from gastrointestinal biopsies is based on cytometric parameters of digitized histological sections. To our knowledge, cytometric parameters of gastritis and of adenocarcinoma have yet to be fully characterized. Our objective was to classify gastritis and adenocarcinoma based on cytometric parameters. We hypothesized that automated virtual microscopy using this novel classification can reliably diagnose gastritis and adenocarcinoma. METHODS: Routinely processed hematoxylin-and-eosin-stained histological sections from specimens that showed normal mucosa (14 cases), gastritis (35 cases), and adenocarcinoma (30 cases) diagnosed by conventional optical microscopy were scanned and digitized at high resolution. Thirty-eight cytometric parameters based on density and morphometry were applied to glands and superficial epithelium. Twelve cytometric parameters based on cytologic detail were applied to individual cells. RESULTS: Statistically significant differences in cytometric parameters for normal mucosa, gastritis, and adenocarcinoma were found. The most discriminatory parameter was the ratio of the total number of cells to the number of interstitial cells. These differences correctly classified adenocarcinoma at 100% accuracy and overall correctness was 86%. CONCLUSIONS: We describe a novel method of analyzing gastric mucosal histology based on cytometric parameters. Automated virtual microscopy can be used to classify gastric mucosa as normal, gastritis, or adenocarcinoma with reasonable accuracy. Further research is necessary to determine whether automated virtual microscopy can subclassify gastric mucosal histology in greater detail.