Morules, or morule-like features, can be identified in benign and malignant lesions in various organs. Morular features are unusual in pulmonary adenocarcinoma cases with only 26 cases reported to date. Here, we describe two cases of pulmonary adenocarcinoma with morule-like features in Korean women. One patient had a non-mucinous-type adenocarcinoma in situ and the other had an acinarpredominant adenocarcinoma with a micropapillary component. Both patients showed multiple intra-alveolar, nodular, whorled proliferative foci composed of atypical spindle cells with eosinophilic cytoplasm. Targeted next-generation sequencing was performed on DNA extracted from formalin-fixed paraffin-embedded samples of the tumors. Results showed unusual epidermal growth factor receptor (EGFR) mutations, which are associated with drug resistance to EGFR tyrosine kinase inhibitors, revealing the importance of identifying morule-like features in pulmonary adenocarcinoma and the need for additional study, since there are few reported cases.
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Background Colorectal cancer (CRC) is one of the most common malignancies worldwide. Approximately 10%–15% of the CRC cases have defective DNA mismatch repair (MMR) genes. Although the high level of microsatellite instability status is a predictor of favorable outcome in primary CRC, little is known about its frequency and importance in secondary CRC. Immunohistochemical staining (IHC) for MMR proteins (e.g., MLH1, MSH2, MSH6, and PMS2) has emerged as a useful technique to complement polymerase chain reaction (PCR) analyses. Methods: In this study, comparison between the MMR system of primary CRCs and paired liver and lung metastatic lesions was done using IHC and the correlation with clinical outcomes was also examined. Results: Based on IHC, 7/61 primary tumors (11.4%) showed deficient MMR systems, while 13/61 secondary tumors (21.3%) showed deficiencies. In total, 44 cases showed proficient expression in both the primary and metastatic lesions. Three cases showed deficiencies in both the primary and paired metastatic lesions. In 10 cases, proficient expression was found only in the primary lesions, and not in the corresponding metastatic lesions. In four cases, proficient expression was detected in the secondary tumor, but not in the primary tumor. Conclusions: Although each IHC result and the likely defective genes were not exactly matched between the primary and the metastatic tumors, identical results for primary and metastatic lesions were obtained in 77% of the cases (47/61). These data are in agreement with the previous microsatellite detection studies that used PCR and IHC.
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Background Mycobacterial culture is the gold standard test for diagnosing tuberculosis (TB), but it is time-consuming. Polymerase chain reaction (PCR) is a highly sensitive and specific method that can reduce the time required for diagnosis. The diagnostic efficacy of PCR differs, so this study determined the actual sensitivity of TB-PCR in tissue specimens.
Methods We retrospectively reviewed 574 cases. The results of the nested PCR of the IS6110 gene, mycobacterial culture, TB-specific antigen-induced interferon-γ release assay (IGRA), acid-fast bacilli (AFB) staining, and histological findings were evaluated.
Results The positivity rates were 17.6% for PCR, 3.3% for the AFB stain, 22.2% for mycobacterial culture, and 55.4% for IGRA. PCR had a low sensitivity (51.1%) and a high specificity (86.3%) based on the culture results of other studies. The sensitivity was higher (65.5%) in cases with necrotizing granuloma but showed the highest sensitivity (66.7%) in those with necrosis only. The concordance rate between the methods indicated that PCR was the best method compared to mycobacterial culture, and the concordance rate increased for the methods using positive result for PCR or histologic features.
Conclusions PCR of tissue specimens is a good alternative to detect tuberculosis, but it may not be as sensitive as previously suggested. Its reliability may also be influenced by some histological features. Our data showed a higher sensitivity when specimens contained necrosis, which indicated that only specimens with necrosis should be used for PCR to detect tuberculosis.
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Background Atypia of undetermined significance (AUS) is a category that encompasses a heterogeneous group of thyroid aspiration cytology. It has been reclassified into two subgroups based on the cytomorphologic features: AUS with cytologic atypia and AUS with architectural atypia. The nuclear characteristics of AUS with cytologic atypia need to be clarified by comparing to those observed in Hashimoto thyroiditis and benign follicular lesions.
Methods We selected 84 cases of AUS with histologic follow-up, 24 cases of Hashimoto thyroiditis, and 26 cases of benign follicular lesions. We also subcategorized the AUS group according to the follow-up biopsy results into a papillary carcinoma group and a nodular hyperplasia group. The differences in morphometric parameters, including the nuclear areas and perimeters, were compared between these groups.
Results The AUS group had significantly smaller nuclear areas than the Hashimoto thyroiditis group, but the nuclear perimeters were not statistically different. The AUS group also had significantly smaller nuclear areas than the benign follicular lesion group; however, the AUS group had significantly longer nuclear perimeters. The nuclear areas in the papillary carcinoma group were significantly smaller than those in the nodular hyperplasia group; however, the nuclear perimeters were not statistically different.
Conclusions We found the AUS group to be a heterogeneous entity, including histologic follow-up diagnoses of papillary carcinoma and nodular hyperplasia. The AUS group showed significantly greater nuclear irregularities than the other two groups. Utilizing these features, nuclear morphometry could lead to improvements in the accuracy of the subjective diagnoses made with thyroid aspiration cytology.
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The authors present the fine needle aspiration cytology (FNAC) cytologic findings of a case of extranodal marginal zone B cell lymphoma (MZBCL), which featured abundant plasma cells and eosinophilic histiocytes arising in both parotid glands. A 49-year-old female presented with palpable masses in both parotid glands. She had been suffering from systemic lupus erythematosus and rheumatoid arthritis. The lesions were evaluated by FNAC and smears showed a small number of clusters of oncocytic cells with abundant eosinophilic granular cytoplasm and small nuclei, intermixed with small to medium-sized lymphoid cells containing round to lobulated nuclei, which suggested Warthin's tumor. Some of lymphoid cells had a plasmacytoid appearance, and some scattered large cells contained a large amount of eosinophilic cytoplasm. Bilateral superficial parotidectomy was performed and a histopathologic study indicated MZBCL with abundant plasma cells, intermixed with eosinophilic histiocytes. The presence of oncocytic cells and a mixture of lymphoid and plasma cells indicates Warthin's tumor, but the cytologic features of a relatively monotonous small to medium-sized lymphoid infiltrate suggest the possibility of MZBCL in the clinical setting of an FNAC study performed on a patient suffering from a connective tissue disease.
Gliosarcoma is a distinct disease entity that is characterized by a biphasic tissue pattern with alternating areas displaying glial and mesenchymal differentiation. The tumor in our case was a rare morphologic variant of gliosarcoma with components of anaplastic oligodendroglioma and unclassifiable spindle cells. Spindle cells showed CD34 and S-100 protein immunoreactivity, which was possibly related to peripheral nerve sheath differentiation. This unique feature has not been described previously and so this case expands the spectrum of possible divergent mesenchymal differentiation, and it lends support to pluripotential stem cells being the origin of this tumor.
Metastasis to the breast from medullary carcinoma of the thyroid is extremely rare. We report a case of metastatic medullary carcinoma of the thyroid which presented as multiple breast masses with ipsilateral axillary lymphadenopathy in a 48-year-old woman. Six years ago, she underwent total thyroidectomy and neck dissection because of palpable neck masses, with a diagnosis of medullary thyroid carcinoma. Histological features of breast masses showed single- file or linear-cord arrangements, with plasmacytoid appearance, and the initial diagnosis was invasive lobular carcinoma. She underwent modified radical mastectomy. The tumor cells were diffusely positive for E-cadherin, calcitonin and thyroid transcription factor-1 (TTF-1) and were metastatic medullary carcinoma of thyroid. In the patients with a history of medullary carcinoma of the thyroid, a careful examination is necessary for a breast mass composed of solid and cord-like clusters of small round to ovoid cells with plasmacytoid appearance.
Immunohistochemical staining for E-cadherin, calcitonin and TTF-1 could be helpful for differential diagnosis.