Lymphoproliferative disorder involving body fluid: diagnostic approaches and roles of ancillary studies.

Lymphocyte-rich effusions represent benign reactive process or neoplastic condition. Involvement of lymphoproliferative disease in body cavity is not uncommon, and it often causes diagnostic challenge. In this review, we suggest a practical diagnostic approach toward lymphocyte-rich effusions, share representative cases, and discuss the utility of ancillary tests. Cytomorphologic features favoring neoplastic condition include high cellularity, cellular atypia/pleomorphism, monomorphic cell population, and frequent apoptosis, whereas lack of atypia, polymorphic cell population, and predominance of small T cells usually represent benign reactive process. Involvement of non-hematolymphoid malignant cells in body fluid should be ruled out first, followed by categorization of the samples into either small/medium-sized cell dominant or large-sized cell dominant fluid. Small/medium-sized cell dominant effusions require ancillary tests when either cellular atypia or history/clinical suspicion of lymphoproliferative disease is present. Large-sized cell dominant effusions usually suggest neoplastic condition, however, in the settings of initial presentation or low overall cellularity, ancillary studies are helpful for more clarification. Ancillary tests including immunocytochemistry, in situ hybridization, clonality test, and next-generation sequencing can be performed using cytologic preparations. Throughout the diagnostic process, proper review of clinical history, cytomorphologic examination, and application of adequate ancillary tests are key elements for successful diagnosis.

Targeted Sequencing Revealed Distinct Mutational Profiles of Ocular and Extraocular Sebaceous Carcinomas.

The biological behavior of sebaceous carcinoma (SeC) is relatively indolent; however, local invasion or distant metastasis is sometimes reported. Nevertheless, a lack of understanding of the genetic background of SeC makes it difficult to apply effective systemic therapy. This study was designed to investigate major genetic alterations in SeCs in Korean patients. A total of 29 samples, including 20 ocular SeCs (SeC-Os) and 9 extraocular SeCs (SeC-EOs), were examined. Targeted next-generation sequencing tests including 171 cancer-related genes were performed. TP53 and PIK3CA genes were frequently mutated in both SeC-Os and SeC-EOs with slight predominance in SeC-Os, whereas the NOTCH1 gene was more commonly mutated in SeC-EOs. In clinical correlation, mutations in RUNX1 and ATM were associated with development of distant metastases, and alterations in MSH6 and BRCA1 were associated with inferior progression-free survival (all p < 0.05). In conclusion, our study revealed distinct genetic alterations between SeC-Os and SeC-EOs and some important prognostic molecular markers. Mutations in potentially actionable genes, including EGFR, ERBB2, and mismatch repair genes, were noted, suggesting consideration of a clinical trial in intractable cases.

Expression of Class III Beta-Tubulin Is Associated with Invasive Potential and Poor Prognosis in Thyroid Carcinoma.

Although American Thyroid Association guidelines offer a risk stratification scheme for thyroid cancer patients, there is a continuous need for more sophisticated biomarkers that can predict disease progression. In this study, we aim to evaluate the prognostic value of class III beta-tubulin (TUBB3) and uncover the relationship between TUBB3 and invasive potential in thyroid carcinoma. Immunohistochemistry (IHC) for TUBB3 and E-cadherin was performed on a total of 254 cases of thyroid cancer specimens. Tumor budding at the invasive margin was evaluated. In vitro functional studies were also performed; the protein and mRNA levels of TUBB3 were compared among the five cell types at baseline, with transwell invasion and after blocking of TUBB3 by shRNA. IHC revealed that the levels of TUBB3 were higher in conventional papillary carcinomas (cPTCs) and anaplastic thyroid carcinomas (ATCs). In univariate analysis, high tumor budding and TUBB3 expression were associated with inferior progression-free survival in cPTC. The results of a Western blot and RT-PCR agreed with the IHC finding. The results were further validated through data from The Cancer Genome Atlas database. Our results suggest that high expression of TUBB3 in thyroid carcinoma could predict invasive potential and possibly be linked with epithelial-mesenchymal transition.

Necrotizing sialometaplasia: a malignant masquerade but questionable precancerous lesion, report of four cases.

BACKGROUND: Necrotizing sialometaplasia (NSM) is an extremely rare benign lesion with an uncertain pathogenesis. The differential diagnosis of this lesion is challenging due to little familiarity with this entity and histologic similarity with carcinomas, especially mucoepidermoid carcinoma (MEC). The purpose of this study is to raise awareness about NSM, which is often overlooked or misdiagnosed as malignancy in a small biopsy. METHODS: We reviewed all biopsy materials taken from the oral cavity in a single institution in Korea from 2012 to 2018 and found 4 cases of NSM out of 726. Clinicopathologic characteristics and comparison with other lesions were discussed. RESULTS: Unlike previous reports, patients in our series were relatively young, and NSM was not related to smoking and not associated with malignancies, although one patient was misdiagnosed with MEC on the basis of the initial biopsy. High-grade squamous dysplasia was observed in one patient; however, all four patients showed excellent prognoses without further management. CONCLUSIONS: A conservative approach is recommendable for necrotizing lesions of the palate in young adults to avoid unnecessary treatment. However, careful monitoring is also required due to uncertainty of premalignant potential.

Characteristics of CD5-positive diffuse large B-cell lymphoma among Koreans: High incidence of BCL2 and MYC double-expressors.

Aberrant expression of CD5 has been reported in 5-10% of diffuse large B-cell lymphomas (DLBCLs). CD5+ DLBCL had been recognized as an aggressive immunophenotypic subgroup of DLBCL in the 2008 WHO classification of haematolymphoid neoplasm; however, it was eliminated from the list of subgroups of DLBCLs in the revised 2016 classification. Nevertheless, there is much controversy regarding the clinical significance of CD5 expression, and many researchers still assert that this subgroup exhibits an extremely unfavorable prognosis with frequent treatment failure. We retrospectively investigated 405 DLBCLs recruited from three university hospitals in Korea from 1997 to 2013. The clinical profile, immunophenotype, and chromosomal structural alterations of the BCL2 and MYC genes were compared according to CD5 expression. A total of 29 cases of de novo CD5+ DLBCL were identified out of 405 in our series (7.4%). Clinicopathologic correlation was performed in all 29 CD5+ DLBCLs and 166 CD5- DLBCLs which were eligible for full clinical review and further pathologic examination. Compared with CD5- counterparts, CD5+ DLBCLs showed female preponderance, frequent bone marrow involvement, higher lactate dehydrogenase level, advanced Ann Arbor stages and poorer prognosis (all p<0.05). Pathologically, the expression of CD5 positively correlated with that of BCL2, MYC and Ki-67 (all p<0.05). Coexpression of BCL2 and MYC, which is referred to as a double-expressor, was relatively more common in CD5+ DLBCL, whereas translocation or amplification of these genes was very rare. in conclusion, the expression of CD5 is an independent poor prognostic factor of DLBCLs, and this subgroup displays unique clinicopathologic features. Although the exact mechanism remains uncertain, consistent activation of BCL2 and MYC by alternative pathways other than chromosomal translocation may contribute to the pathogenesis.

Sonographic and Clinical Characteristics of Uterine Sarcoma Initially Misdiagnosed as Uterine Fibroid in Women in the Late Reproductive Age.

OBJECTIVES: Uterine sarcoma is a rare malignant tumor, which is usually diagnosed in postmenopausal women. These sarcomas are occasionally misdiagnosed as uterine fibroids, thereby leading to delayed diagnosis in the advanced stages. We analyzed the sonographic and clinical characteristics of unexpected uterine sarcomas detected after surgery in women in the late reproductive age. METHODS: The medical records of 61 patients preoperatively diagnosed with uterine leiomyomas through sonography but confirmed as uterine sarcomas after surgery from January 2005 to December 2018 at Asan Medical Center were retrospectively analyzed. We evaluated the clinical symptoms, sonographic findings, and Doppler indexes, and investigated whether there were any significant characteristics that could clearly differentiate uterine sarcoma from fibroids. RESULTS: The most common clinical finding was increased mass size (15 patients, 24.6%), while 9 patients (14.8%) showed no symptoms. Ultrasonography showed that the maximum diameter of most fibroids was > 5 cm (49 patients, 80.3%), and the average diameter was 75.6 ± 36.3 mm. All the patients showed heterogeneous echogenicity in sonographic imaging. Secondary degeneration of the myomas was reported in 36 patients (59%), and approximately 90% (32/36, 88.9%) showed cystic changes. Of the 40 patients who underwent the evaluation of vascularity, 35 showed increased vascularity of the mass. CONCLUSIONS: In this study, sarcomas misdiagnosed as leiomyomas were usually > 5 cm, and ultrasonography showed heterogeneous echogenicity and irregular cystic degeneration. No definite clinical symptoms were helpful; a thorough evaluation is necessary to rule out uterine sarcomas in women having uterine mass with these characteristics.

The Expression of Adipophilin Is Frequently Found in Solid Subtype Adenocarcinoma and Is Associated with Adverse Outcomes in Lung Adenocarcinoma.

BACKGROUND: The up-regulation of the lipogenic pathway has been reported in many types of malignant tumors. However, its pathogenic role or clinical significance is not fully understood. The objective of this study was to examine the expression levels of adipophilin and related hypoxic signaling proteins and to determine their prognostic impacts and associations with the pathologic characteristics of lung adenocarcinoma. METHODS: Expression levels of adipophilin, heat shock protein 27 (HSP27), carbonic anhydrase IX, and hypoxia-inducible factor 1α were examined by immunohistochemical staining using tissue microarray blocks. Correlations between protein expression levels and various clinicopathologic features were analyzed. RESULTS: A total of 230 cases of primary adenocarcinoma of the lung were enrolled in this study. Adipophilin expression was more frequent in males and with the solid histologic type. It was correlated with HSP27 expression. Patients with adipophilin-positive adenocarcinoma showed a shorter progression-free survival (PFS) (median PFS, 17.2 months vs 18.4 months) in a univariable survival analysis, whereas HSP27 positivity correlated with favorable overall survival (OS) and PFS. In a multivariable analysis, adipophilin and HSP27 were independent prognostic markers of both OS and PFS. CONCLUSIONS: Activated lipid metabolism and the hypoxic signaling pathway might play a major role in the progression of lung adenocarcinoma, especially in the solid histologic type.

Brainstem astroblastoma with MN1 translocation.

Astroblastoma is a rare glial neoplasm that occurs mostly in the cerebral hemisphere of children, adolescents and young adults. Although astroblastic perivascular pseudorosettes are unique histopathology of this neoplasm, diagnosis is usually challenging. Recently, it was discovered that the meningioma 1 gene (MN1)-altered pediatric central nervous system high-grade neuroepithelial tumors are actually astroblastomas. This case report presents a rare brainstem astroblastoma, with an unusual immunoprofile: negative for glial fibrillary acidic protein and oligodendrocyte transcription factor 2, but with a robust expression of pancytokeratin and epithelial membrane antigen. The diagnosis was confirmed based on the detection of MN1 rearrangement in a fluorescence in situ hybridization study, in addition to typical histopathology. Here we discuss the diagnostic pitfalls and unclear grading system along with a literature review.

Perivascular Epithelioid Cell Tumor in the Stomach.

Perivascular epithelioid cell tumors or PEComas can arise in any location in the body. However, a limited number of cases of gastric PEComa have been reported. We present two cases of gastric PEComas. The first case involved a 62-year-old woman who presented with a 4.2 cm gastric subepithelial mass in the prepyloric antrum, and the second case involved a 67-year-old man with a 5.0 cm mass slightly below the gastroesophageal junction. Microscopic examination revealed that both tumors were composed of perivascular epithelioid cells that were immunoreactive for melanocytic and smooth muscle markers. Prior to surgery, the clinical impression of both tumors was gastrointestinal stromal tumor (GIST), and the second case was erroneously diagnosed as GIST even after microscopic examination. Although gastric PEComa is a very rare neoplasm, it should be considered in the differential diagnosis of gastric submucosal lesions.