High-yield areas to grade tumor budding in colorectal cancer: A practical approach for pathologists.

BACKGROUND: Tumor budding (TB) has significant prognostic implication in stage II colorectal cancer (CRC) and is graded based on the International Tumor Budding Consensus Conference (ITBCC) protocol. In the current study, we evaluate tumor budding and its relationship to multiple histologic features in 104 tumors. METHODS: One-hundred four resected CRC cases were retrieved. Tumor bud count and TB grade were compared to the final tumor bud count/TB grade of the tumor per ITBCC protocol. The following high-yield co-features were assessed in each slide: highest T stage, presence of benign mucosa, presence of a precursor lesion, and highest tumor volume. RESULTS: Twenty-nine (28 %) cases had discrepancies between slide TB grade and final TB grade. The least discrepancies were seen in slides with benign mucosa (7 %) and precursor lesions (7 %). Among stage II patients without high-risk features, no discrepancies were observed in slides with benign mucosa. Slides with deepest invasion (rs = 1.000, p = 0.01) and benign mucosa (rs = 0.957, p < 0.001) had the strongest correlation with final tumor bud count in the same stage II subgroup. Similar relationships were observed when comparing final TB grade. Deepest invasion, tumor volume, as well as lymphovascular invasion, when present, also showed strong correlations with final TB grade in the entire cohort (rs = 0.828-0.845, p < 0.001). CONCLUSION: Our study is the first study to evaluate the relationship between TB grade and co-existing histologic features. We highlight the benefit of focusing on slides with high-yield co-features, with the strongest correlation seen in slides with adjacent benign mucosa and precursor lesions.

Histologic Findings and Tissue B-Cell Depletion in Endoscopic Mucosal Biopsy Specimens of the Gastrointestinal Tract After Treatment With Rituximab.

OBJECTIVES: Rituximab (RTX) is associated with variable adverse gastrointestinal (GI) events. However, the histologic correlate in affected patients is not well defined. METHODS: Patients (n = 93) who had received RTX and undergone endoscopic biopsies were identified. CD20 and PAX5 immunostains were performed on biopsy specimens showing inflammatory pathology (group A, 36 patients) and 35 of 57 noninflammatory biopsies (group B) that were taken within 1 year from the last RTX infusion. Histologic findings were correlated with tissue B-cell depletion (CD20/PAX5-/-). RESULTS: B cells were depleted in 12 (33%) of 36 group A biopsy specimens. After excluding biopsies taken more than 1 year from the last RTX infusion, the frequencies of tissue B-cell depletion were similar between group A (12/26; 46.2%) and group B (17/35; 48.6%) (P > .05). Also, the frequencies of inflammatory pathology were not statistically different whether B cells were depleted or not (P > .05). In group A with tissue B-cell depletion (n = 12), causality was indicated in two (17%) cases showing lymphocytic colitis pattern of injury (LCPI). CONCLUSIONS: In RTX-treated patients, tissue B-cell depletion does not appear to be the main cause of inflammatory pathology in the GI tract. A minor subset, however, develops histologic evidence of potential RTX-induced effect, notably in the form of LCPI.

Benign vs malignant pancreatic lesions: Molecular insights to an ongoing debate.

Several benign conditions such as chronic pancreatitis, autoimmune pancreatitis, and paraduodenal pancreatitis can present as mass lesions and may mimic pancreatic ductal adenocarcinoma (PDAC) clinically and radiologically. Thorough histologic examination with attention to certain morphologic features can assist in deciphering neoplastic from reactive, however small biopsies often remain a challenge. Variable histologic patterns in conventional PDAC may also confound the diagnosis of PDAC. Uncommon subtypes of pancreatic carcinoma such as adenosquamous and squamous cell carcinoma, colloid carcinoma, medullary carcinoma, hepatoid carcinoma and signet ring cell carcinoma necessitate excluding metastasis from other sites prior to rendering the diagnosis of pancreatic carcinoma. The use of immunohistochemical staining and molecular markers can aid in separating benign from malignant and PDAC from metastasis. PDAC expresses a few non-specific epithelial and mucin immunomarkers such as CK7, CK19, MUC1, MUC4 and MUC5AC. However, the only immunohistochemical marker that is specific for PDAC in the right clinical context is SMAD4. Loss of SMAD4 within atypical glands and ducts supports the diagnosis of PDAC in a limited sample. Unfortunately, this finding is seen only in 50% of PDAC cases. The identification of certain mutations can help support a diagnosis of PDAC when benign conditions are in the differential. At the molecular level, KRAS oncogene mutations are seen in approximately 93% of PDACs. Subsequent neoplastic progression is driven by additional mutations of tumor suppressor genes, such as CDKN2A, TP53, and SMAD4. Molecular markers can also provide an insight to the prognosis. For instance, the loss of SMAD4 is associated with a poor outcome whereas mutations in MLL, MLL2, MLL3, and ARID1A are associated with improved survival.

Composite intestinal adenoma-microcarcinoid: An update and literature review.

Composite intestinal adenoma-microcarcinoid (CIAM) is a rare intestinal lesion consisting of conventional adenoma and small, well differentiated carcinoid [microcarcinoid (MC)] at its base. The incidence of CIAM is 3.8% in surgically resected colorectal polyps. While its pathogenesis is unknown, studies support the role of Wnt/ß-catenin pathway in the tumorigenesis of CIAM. CIAMs have been primarily reported in the colon wherein they present as polyps with well-defined margins, similar to conventional adenomatous polyps. MC is usually found in adenomatous polyps with high-risk features such as large size, villous architecture, or high grade dysplasia. Histologically, the MC component is often multifocal and spans 3.9 to 5.8 millimeters in size. MC is usually confined within the mucosa but occasional CIAM cases with MC extending to the submucosa have been reported. MC of CIAM demonstrates bland cytology and inconspicuous proliferative activity. The lesional cells are positive for synaptophysin and 60% to 100% of cases show nuclear ß-catenin positivity. MC poses a diagnostic challenge with its morphologic and immunohistochemical resemblance to both benign and malignant lesions, including squamous morules/metaplasia, adenocarcinoma, squamous cell carcinoma, sporadic neuroendocrine tumor and goblet cell adenocarcinoma. CIAM is an indolent lesion with a favorable outcome. Complete removal by polypectomy is considered curative. Awareness and recognition of this rare entity will help arrive at correct diagnosis and improve patient care. Currently, CIAM is not recognized as a subtype of mixed neuroendocrine-non-neuroendocrine neoplasm by WHO.

Absence of contrast enhancement in a petroclival meningioma: Case report and systematic literature review.

BACKGROUND: Meningioma is one of the most common intracranial tumors with well-established radiologic features such as contrast enhancement, dural tail, and hyperostosis on computed tomography and magnetic resonance imaging. Contrast enhancement is usually homogeneous or heterogeneous based on tumor vascularity and underlying histopathology. Even in this context, faint or nonenhancing meningioma is exceedingly rare. CASE DESCRIPTION: A 57-year-old male presented with progressive right hearing loss, disequilibrium, occasional difficulty swallowing, and facial numbness. Imaging demonstrated an extensive hypodense, nonenhancing right cerebellopontine angle mass extending from the interpeduncular, and ambient cisterns to the foramen magnum. The pathological analysis demonstrated a microcystic meningioma WHO Grade I. There are few reported case reports or series of minimal or nonenhancing meningiomas, and a systematic review was performed for these cases. Seven peer-reviewed articles with 14 verifiable cases were identified and reviewed for radiologic features, tumor location, and tumor classification. The majority of minimal or nonenhancing meningiomas were microcystic, and most of them located at the convexity. This is the second case reported of a nonenhancing meningioma at the cerebellopontine angle and petroclival region. CONCLUSION: Meningioma should be considered a differential diagnosis for nonenhancing lesion at the cerebellopontine and petroclival regions.

Lymphocytic colitis pattern of injury presenting as endoscopic polyps: a case series.

Lymphocytic colitis (LC) is characterized by chronic watery diarrhea and unremarkable endoscopic findings. Only one case of LC presenting as multiple colonic polyps has been reported. We report a case series of histologic LC pattern of injury (LCPI), presenting as endoscopic polyps, and compare them with typical LC cases. Eighteen archived (2009-2019) polypoid LCPI cases without an associated cause of polyp, such as adenoma, hyperplastic change, or lymphoid aggregate, were retrieved from 17 (12 female and 5 male) patients. The clinical history and endoscopic findings were noted. A total of 40 conventional LC cases were used as controls. Fisher's exact test was performed to evaluate associations between two variables. The mean age of the patients was 61.1 years. The indication for colonoscopy was chronic watery diarrhea (56%), screening/surveillance (33%), and rectal bleeding (11%). The mean number and size of the polyps was 1.6 and 2.9 mm, respectively. Seventy-six percent were located in the left colon, and 48% were sessile. When biopsied (14/18; 78%), the background colonic mucosa showed LCPI. There was no significant difference in age, gender, and the average number of lymphocytes in the two groups. Hypertension and history of malignancy was more common in the polypoid LCPI group than in the control LC group (P < 0.05). LCPI may present as endoscopic polyps, frequently in patients with hypertension and history of malignancy. Polypoid LCPI may be a harbinger of LCPI in the background nonpolypoid colonic mucosa. A subset of polypoid LCPI (56%) cases represents true LC.

Kratom-Induced Cholestatic Liver Injury Mimicking Anti-Mitochondrial Antibody-Negative Primary Biliary Cholangitis: A Case Report and Review of Literature.

Kratom is an herbal supplement used to relieve chronic pain or opioid withdrawal symptoms. Recent news articles covering adverse effects associated with kratom use have brought attention to its organ toxicities. Reports of kratom-induced hepatic toxicity are limited and only three case reports of kratom-induced liver injury with histopathologic examination of the liver biopsies are available. A 40-year-old female presented with symptoms of mixed cholestatic and hepatocellular liver injury without clear etiology. The laboratory and imaging workup suggested possibilities of autoimmune hepatitis, autoimmune hepatitis-primary biliary cholangitis (PBC) overlap syndrome, or drug-induced liver injury. Autoantibodies including anti-mitochondrial antibody (AMA) were negative. Liver biopsy showed granulomatous hepatitis with prominent duct injury, suggestive of AMA-negative PBC. She subsequently was referred to a hepatologist and a history of recent kratom use was finally revealed. Kratom was discontinued and the symptoms improved. Kratom-induced hepatic toxicity may manifest with variable biochemical and clinical abnormalities. Histologically, it may mimic AMA-negative PBC. Our case highlights the importance of thorough history taking, interdisciplinary approach and communication for optimal patient care.