Turkish Journal of Pathology最新文献

Objective: The classification of renal tumors is expanding with the addition of new molecular entities in the 5th World Health Organization classification. Apart from this, the major updates in the definition of papillary renal cell carcinoma are that these tumors are no longer subtyped into type 1 and type 2. In oncocytic tumors, the new molecularly defined renal tumors, emerging and novel entities need to be considered in the diagnosis of oncocytic and chromophobe renal tumors.

Material and methods: This is a retrospective study to review and reclassify papillary, oncocytic, and chromophobe renal tumors based on the new WHO classification and correlate with clinical data, gross, microscopic features, and immunohistochemistry markers.

Results: A total of thirteen cases were reviewed and the tumor grade was changed for three out of four cases of papillary renal cell carcinoma and a single case was recategorized and graded. In nine cases of oncocytic and chromophobe renal tumors, the diagnoses were modified in 3 cases.

Conclusion: Newly defined molecular renal tumors require advanced immunohistochemistry markers and molecular tests. This poses diagnostic challenges to pathologists practicing in low resource settings where molecular tests are not available.

Objective: SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a highly malignant neoplasm with an undifferentiated or rhabdoid phenotype, posing a diagnostic challenge. This case report aims to create awareness about this rare neoplasm while dealing with cases presenting with undifferentiated morphology.

Case report: A 55-year-old gentleman with constitutional symptoms and lymphadenopathy. Imaging revealed a mass lesion in the right upper lobe of the lung. A biopsy of the cervical lymph node showed diffusely effaced architecture replaced by sheets of undifferentiated pleomorphic cells with vesicular nuclei, prominent nucleoli, eosinophilic cytoplasm, and multiple necrotic foci. An extensive immunohistochemistry (IHC) panel was applied, which showed positivity for synaptophysin, vimentin, and focal CD34 and EMA expression. Other markers like pan-cytokeratin, p40, TTF1, CD56, INSM1, calretinin, CD45, SOX10, S100, CD30, CD117, SMA, and Desmin were negative, with INI1 retained. The IHC panel excluded the morphological differentials of carcinoma, lymphoma, rhabdomyosarcoma, melanoma, and germ cell tumor. Further literature review led to the possibility of the SMARCA4-UT entity, which had a morphology and IHC profile similar to the present case. Testing for SMARCA4 (BRG-1) by IHC showed a complete loss in the tumor cells, favoring the diagnosis of Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT).

Conclusion: SMARCA4-UTs are rare, highly aggressive, and poorly differentiated thoracic tumors. Recognizing them is vital as there is potential for therapeutic interventions such as immunotherapy and SMARCA4-targeted therapies, offering promising prospects for the future.

Approximately 95% of cervical squamous cell carcinomas are associated with high-risk HPV, with a small number of HPV-independent tumors. However, low-risk HPV types have also been detected in rare cervical squamous cell carcinomas. Low-grade squamous intraepithelial lesion-related changes are a rare morphologic finding in cervical squamous cell carcinoma. We present the case of a 30-yr-old woman who presented with pelvic pain and foul-smelling vaginal discharge showing an exophytic lesion protruding from the cervix. Repeated superficial biopsies showed a low-grade squamous intraepithelial lesion (LSIL) characterized by binucleation and koilocytosis. Chromogenic in-situ hybridization revealed the presence of HPV6/11. The absence of high-risk HPV was confirmed by PCR. After following the patient for nine months without intervention, type III hysterectomy and bilateral pelvic paraaortic lymphadenectomy were performed. Microscopic examination showed well-differentiated squamous cell carcinoma with solid epithelial islands and extensive eosinophilic cytoplasm without pleomorphism. HPV 6 and 11 were also detected with chromogenic in-situ hybridization. Neoplasm invaded the full-thickness of the cervical wall and infiltrated the vagina, parametrium, the proximal ureter and bladder. The patient who received chemoradiotherapy is disease-free at 36 months follow-up. Low-risk HPV-related well-differentiated invasive squamous lesions exist, and such lesions could be a diagnostic pitfall for gynecologists and pathologists; in these cases, radiologic-pathologic correlation and radiologic guided biopsy are mandatory.

Objective: The gold-standard method for assessment of autoimmune bullous disease is direct/indirect immunofluorescence (IF) examination applied to fresh frozen tissue. Since the sensitivity of IF is greatly reduced in formalin-fixed paraffin-embedded (FFPE) tissues, IF cannot be relied upon in these samples. However, immunohistochemistry with the C4d antibody is a promising marker used as a surrogate for immune complex deposition, in nephropathology practice, and the paraffin IF method is also used as a `salvage` technique when fresh frozen tissue is not available or lacks glomeruli. We aimed to investigate whether it is possible to obtain immunofluorescence data from FFPE tissues diagnosed with bullous pemphigoid (BP) and pemphigus vulgaris (PV) and its relationship with inflammatory parameters in the skin.

Material and methods: Eighty-nine in-house cases with both IgG and C3 positivity by routine immunofluorescence examination were included in the study. Inflammation parameters were evaluated in hematoxylin-eosin sections. Immunofluorescence study with IgG protease digestion and C4d immunohistochemistry were performed.

Results: Results of 83 biopsies were obtained by paraffin immunofluorescence with IgG. There were positive reactions in 28 (34%) of these 83 biopsies. Five of the 28 positive results belonged to BP (18%), and 23 were PV (82%). Ten positive results were on lesional skin (36%), and 18 (64%) were on non-lesional skin. In the immunohistochemical study with C4d, 84 biopsy results were obtained. There were positive reactions in 34 (40.4%) of 84 biopsies. Of the 34 positive results, 12 belonged to BP (35.3%) and 22 to PV (64.7%). Again, 22 (64.7%) of 34 positive results belonged to lesional skin, and 12 (35.3%) belonged to non-lesional skin. When both techniques were used together, 44 (54%) of 81 biopsies yielded positive results for at least one of the two studies, while in 37 (46%), both tests showed negative results.

Conclusion: The sensitivity of both IgG and C4d was less than in the literature, especially in BP-diagnosed biopsies. Positive samples were mostly PV. In conclusion, obtaining immunofluorescence data in FFPE samples is possible and is independent of the related skin being lesional or not, however, negative results should not be relied upon.

Objective: Alterations in the expression of several long non-coding RNAs (lncRNAs) have been shown in chronic hepatitis B-associated hepatocellular carcinoma (CHB-HCC). Here, we aimed to investigate the association between the expression of inflammation-associated lncRNA X-inactive specific transcript (XIST) and the type of inflammatory cells within the tumor microenvironment.

Material and methods: Twenty-one consecutive cirrhotic patients with CHB-HCC were included. XIST expression levels were investigated on formalin-fixed paraffin-embedded (FFPE) tumoral and peritumoral tissue samples by real-time polymerase chain reaction (RT-PCR). Immunohistochemical staining for CD3, CD4, CD8, CD25, CD163, CTLA4, and PD-1 were performed. The findings were statistically analyzed.

Results: Of the 21 cases, 11 (52.4%) had tumoral and 10 (47.6%) had peritumoral XIST expression. No significant association was found between the degree of inflammation and XIST expression. The number of intratumoral CD3, CD4, CD8 and CD20 positive cells was higher in XIST-expressing tumors, albeit without statistical significance. Tumoral and peritumoral XIST expression tended to be more common in patients with tumoral and peritumoral CD4high inflammation. The number of intratumoral CD25 positive cells was significantly higher in XIST-expressing tumors (p=0.01). Tumoral XIST expression was significantly more common in intratumoral CD25high cases (p=0.04). Peritumoral XIST expression was also more common among patients with CD25high peritumoral inflammation, albeit without statistical significance (p=0.19).

Conclusion: lncRNA XIST is expressed in CHB-HCC and its expression is significantly associated with the inflammatory tumor microenvironment, particularly with the presence and number of CD25 (+) regulatory T cells. In vitro studies are needed to explore the detailed mechanism.

Objective: Epstein-Barr Virus-Associated Smooth Muscle Tumor (EBV-SMT) is a rare tumor with a higher rate of occurrence in unusual locations in the setting of immunodeficiency. In this study, we evaluated a cohort of ordinary leiomyosarcomas (LMS) for the presence of EBV and described the clinicopathological features deviating from routinely diagnosed cases of EBV-SMT.

Material and method: The sections of tissue microarrays including 93 classical LMS occurring in various locations were hybridized with EBER and stained for LMP1 antibody using the Leica Bond Autostainer. EBV real-time PCR assay was performed in 2 EBER-positive cases.

Results: Among the 93 LMS cases, 2 non-uterine cases (2.2%) were positive for EBER and negative for LMP1, and were referred to as `EBV-positive LMS`. Both were females in their 6th decade without immunosuppression. EBV real-time PCR assay revealed the presence of EBV in one of the cases. Tumors were located in the pancreas and chest wall. Morphologically, tumors were rather myxoid, multinodular, and composed of long fascicles of spindle cells with intermediate- to high-grade features. High mitotic activity and focal necrosis were present, whereas no accompanying lymphocytes were detected. One of the patients developed metastatic disease after 3 years.

Conclusion: EBV-positive LMS occurring in immunocompetent patients has features distinct from classical EBV-SMT seen in immunosuppressed patients.

To document a case of `preliminary` identification of Alternaria sp (a phaeohyphomycotic agent) based on morphology in tissue section in a patient with allergic fungal rhinosinusitis. A 25-year-old male, a known asthmatic in a post Covid -19 state, presented with headache, facial swelling and nasal block with discharge of brownish mucoid material. Debrided material from the right maxillary antrum and middle turbinate showed brownish mucoid material admixed with firm to hard degenerated bony spicules sent in formalin and subjected for histopathological examination. Histopathology showed fragments of tissue, mucoid material, degenerated bony spicules, and blood clots. Amidst ulcerated epithelium and mucoid debris were seen scattered pigmented fungi in a state of `vegetative sporulation` with characteristic brownish multicellular `macroconidia` diagnostic of Alternaria sp. A diagnosis of `Phaeohyphomycosis` possibly due to Alternaria sp was offered. The patient was treated with Amphotericin B. The patient was lost to follow up. Clinical materials such as tissue sections or smears from nasal mucus secretions in cases of allergic fungal rhinosinusitis provide a very good source for `preliminary` identification of species and early institution of therapy while waiting for the fungal culture report.

Objective: Squamous cell carcinoma (SCC) of the urinary bladder is associated with aggressive behavior and is typically treated with radical cystectomy. Vitamin D receptor (VDR) and its ligand Calcitriol have shown anti-tumor effects in various malignancies but to our knowledge there is no current information on VDR expression in bladder SCC. This study aimed to assess VDR immunostaining patterns in pure bladder SCC and its relation to the available clinicopathological parameters of such tumors.

Material and methods: VDR immunostaining was performed on 35 radical cystectomy specimens from patients with primary pure SCC. Nuclear and cytoplasmic VDR staining was scored separately using the semi-quantitative immunoreactive score.

Results: Nuclear and cytoplasmic/membranous VDR expression was present in 35 (100%) and 19 (54.3%) cases, respectively, with a significant negative linear relationship (r=-0.33; p=0.035). Differences in cytoplasmic/membranous VDR expression were found in relation to tumor histology (p=0.018), tumor necrosis (p=0.022), and stage groups (p=0.001). Low cytoplasmic VDR correlated with increased tumor staging (Cc = -0.422), positive lymph node status (Cc = -0.375), and higher stage groups (Cc= -0.438). The median nuclear VDR expression score was significantly higher in advanced stage groups (p= 0.038).

Conclusion: Our data suggest that VDR may be a potential prognostic factor in bladder SCC. Further studies and clinical trials using vitamin D supplements may provide a new therapeutic option for those high-risk patients.

Objective: Abdominal wall masses often pose diagnostic challenges for clinicians due to their nonspecific symptoms. They include a wide spectrum of lesions ranging from inflammatory to tumor-like masses and malignancies. The majority of the malignant nodules are metastatic in origin and may be the initial presentation of a primary malignancy; hence, an early diagnosis is important. Fine-needle aspiration cytology (FNAC) is a valuable diagnostic tool in the evaluation of such lesions. This was a retrospective study of the cytomorphological spectrum of abdominal wall masses, conducted at a tertiary health care centre over a three-year period.

Material and methods: The study included patients of all age groups presenting with an abdominal wall mass. These lesions were assessed by FNAC. The diagnosis was made on cytology smears and subsequently correlated with the histopathological diagnosis, wherever possible.

Results: Of the 70 cases, 21 were non-neoplastic and 49 neoplastic. A benign neoplasm was the most common lesion (52.9%), followed by non-neoplastic lesions (30%) and malignant neoplasms (17.1%). Lipoma was the most common benign neoplasm and metastasis was the commonest malignant neoplasm. The most common type of tumor metastasising was adenocarcinoma and the primary tumors were predominantly intra-abdominal. No false-negative results were seen.

Conclusion: Most of the abdominal wall masses display a characteristic cytomorphology, which needs to be identified and recognized by a cytopathologist for an accurate diagnosis. FNAC plays an invaluable role in the detection of metastases, especially at sites such as the umbilicus, which may be the only manifestation of an underlying advanced malignant disease.

Objective: Histoplasmosis is a systemic, deep mycotic infection caused by Histoplasma capsulatum. Disseminated histoplasmosis (DH) is synonymous with HIV seropositive immunocompromised individuals; however, isolated histoplasmosis involving the head and neck mucosal sites mimicking malignancy is a clinical predicament. The result, in a superficial biopsy with marked pseudoepitheliomatous hyperplasia (PEH), in a tertiary care cancer center where the number of squamous carcinomas far outnumber the infectious diseases, could be catastrophic.

Material and method: The archives of a tertiary care cancer hospital were searched (2010-2019) for cases of histoplasmosis involving the head and neck mucosal sites in HIV non-reactive patients.

Results: Six cases of isolated head and neck histoplasmosis were seen in biopsies from 4 men and 2 women, with an age range of 46-72 years. Three of these patients suffered from chronic illnesses. The most common site involved was the larynx (vocal cords) in three cases, two cases were involving lips, and one involving the tongue. The biopsies were reviewed in-house with a clinical diagnoses of malignancy in all and an outside biopsy diagnosis of "squamous cell carcinoma" in 2 cases. The important histological findings in the biopsy were PEH (3 cases), granulomas (2 cases), lymphoplasmacytic inflammation (all cases). Eosinophils were conspicuous by their absence. Intracellular histoplasma was seen in all cases, albeit to varying density, which was confirmed with GMS stain.

Conclusion: A high index of suspicion, meticulous history taking by oncologists, and appropriate distinction of PEH from neoplastic squamous proliferation by pathologists in superficial biopsies and an apropos deeper wedge biopsy are essential to clinch the correct diagnosis.