N-Nitrosomorpholine-induced oncocytic transformation in rat endocrine organs.

BACKGROUND: N-Nitrosomorpholine (NMO) is one of the most common N-nitroso compounds. An oncocytic transformation has been demonstrated in renal tubules of NMO-treated rats. In our study, we aimed to investigate the potential transformation of oncocytic cells in 6 endocrine organs, i.e., thyroid, adrenal and pituitary glands, pancreas, testis, and bone, of NMO-exposed rats. METHODS: Thirty male rats were born and raised. Fifteen of them were given a single dose of 320 mg NMO per kg body weight, dissolved in drinking water, by a gavage tube. At the end of 52 weeks, the animals in both series were killed. Right after the killing, 6 different endocrine organs (hypophysis, thyroid, pancreas, adrenal gland, bone [femur], and testicles) of each animal were excised. RESULTS: There was no evidence of oncocytic cell development in the control group. In contrast, oncocytes were observed in 8 out of 13 NMO-treated rats: 2 in the adrenal sections, 1 in the thyroid sections, 3 in the pituitary sections, and 2 in the pancreas sections. Thesticle and bone sections were completely normal. CONCLUSIONS: We showed that NMO induced an oncocytic change in pancreas, thyroid, pituitary, and adrenal glands. To date, no identified specific environmental risk factors that lead to an oncocytic transformation in endocrine glands have been reported previously. Given the increasing prevalence of endocrine-disrupting chemicals in the environment, personal care products, manufactured goods, and food sources, there is a need to advance our understanding of the pathological mechanisms underlying oncocytosis in endocrine organs.

Plexiform neurofibroma (Hamartoma) of the median nerve: A two-case report.

Plexiform neurofibroma is a benign peripheral nerve-sheath tumor, rarely involving major nerves of the extremities. In the literature, there are no clear treatment strategies for plexiform neurofibroma of major peripheral nerves. Our experience encountered two patients with plexiform neurofibroma of the median nerve, presenting with a palmar mass and symptoms of carpal tunnel compression. Preoperatively, plexiform neurofibroma was diagnosed on MRI and clinical examination. Both patients also experienced significant neurological deterioration, with finger numbness and increased nerve/tumor size. Potential malignant transformation was also considered. For these reasons, resection of the involved area of the nerve and repair were indicated. In both patients, intraoperative pathological diagnosis was plexiform neurofibroma. The 45-year-old male patient refused further surgery after carpal tunnel release, which was performed under axillary block. One year postoperatively, nerve compression symptoms decreased moderately. In the other patient, a 7-year-old boy, a significantly enlarged area of the median nerve was resected, and neurorrhaphy was performed. One year postoperatively, median nerve motor-sensory functions recovered completely. Four years postoperatively, no enlargement of the residual tumor was observed.

Detailed fine needle aspiration cytopathology findings of noninvasive follicular thyroid neoplasm with papillary-like nuclear features with nuclear grading correlated to that of biopsy and Bethesda category and systematic review.

BACKGROUND: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) poses diagnostic challenge in fine needle aspiration cytopathology (FNAC). We aimed first to document our FNAC Bethesda categories (BCs) for all of our NIFTPs and compare our findings with those in the literature with series containing at least 14 cases each. METHODS: Cases with final histopathological diagnoses of NIFTP and their preoperative FNAC were retrieved from 2006 to 2022 and our cytopathological BCs were documented. Then the slides were re-reviewed in a blinded manner for detailed classification and the results of both the BCs and blinded reclassification were compared with series in the literature for both BCs and detailed cytopathological review of the cases. RESULTS: Thyroid FNACs of 43 out of 86 patients with final NIFTP diagnoses were obtained. Females composed 72.1% (F/M: 31/12); mean age and mean tumor diameter was 47.6 (19-72 years) and 23.4 mm (7-60 mm), respectively. Totally 81.4% (35/43) were classified in the "indeterminate" diagnostic categories; namely 44.2% (19/43) were reported as atypia of undetermined significance (AUS; BC III), 20.9% (9/43) were follicular neoplasm (FN; BC IV), and 16.3% (7/43) were suspicious for malignancy (SM; BC V). No patient was diagnosed as positive for malignancy (BC VI), preoperatively. Detailed cytomorphologic reevaluation revealed heterogeneous cytopathologic findings and nuclear grade (especially nuclear enlargement, membrane irregularity and elongation) significantly increased with respect to BCs. Systematic review confirmed extremely heterogeneous cytomorphologic nature of NIFTP. CONCLUSIONS: NIFTPs were categorized most frequently as AUS, followed by FN and SM on FNAC. Our re-review were not able to specify features solely unique to NIFTP alone but may distinguish these cases from classic papillary thyroid carcinoma.

Silibinin Effect on Methotrexate-Induced Hepatotoxicity in Rats.

OBJECTIVE: Hepatotoxicity is one of the major side effects of methotrexate and limits its use. In this study, we investigated the hepatoprotective effect of silibinin and the role of oxidative stress markers and cytokines on high-dose methotrexate-induced hepatotoxicity in rats. MATERIALS AND METHODS: In this study, rats were randomly divided into 5 groups (n=7). Methotrexate (20 mg/kg, intraperitoneally) was administered on the first day in all groups except control. Silibinin was injected for 5 days to methotrexate-silibinin25, methotrexate-silibinin50, and methotrexate-silibinin100 groups at a dose of 25, 50, and 100 mg/kg/day, respectively. On the sixth day, blood and liver samples were obtained and rats were sacrificed. Serum total antioxidant capacity, total oxidant status, total thiol, native thiol, alanine aminotransferase, aspartate transaminase, bilirubin, albumin, tumor necrosis factor-alpha, and interleukin-10 levels were measured. In addition, a histopathological evaluation of liver tissues was performed. RESULTS: Methotrexate reduced total antioxidant capacity and increased disulfide/total thiol ratio. Histopathologic examination revealed that methotrexate increased hepatic damage and 50 mg/kg/dose of silibinin prevented inflammatory cell infiltration in particular. CONCLUSION: Our results suggest that silibinin (50 mg/kg/day) may reduce the hepatic damage in methotrexate-induced hepatotoxicity in rats by increasing antioxidant capacity.

The Value of Immunohistochemical Methods and Preoperative Magnetic Resonance Imaging Findings in Diagnosis of IDH1 Mutant Glioblastomas.

AIM: To assess the presence of isocitrate dehydrogenase (IDH) 1 mutation in glioblastomas using real-time polymerase chain reaction (RT-PCR), which is the gold standard in the diagnosis of IDH1 mutation; by immunohistochemistry (IHC), which is available in most of the pathology laboratories; and by preoperative magnetic resonance imaging, which is a non-invasive method. We also investigated the relationship between these methods and their usability in routine practice. MATERIAL AND METHODS: RT-PCR was performed to evaluate the presence of IDH1-R132H mutation on the blocks of 70 patients diagnosed with glioblastoma, and IDH1 stain was applied to the same blocks as IHC. Radiologically, preoperative magnetic resonance images of the patients were reviewed in terms of tumor size, localization, and presence of non-contrast-enhancing solid tumor component. RESULTS: Evaluation by RT-PCR revealed that 15 (21.4%) patients were IDH-mutant, whereas IHC examination revealed 13 (18.6%) and radiological evaluation revealed 11 (15.7%) patients were IDH-mutant. There was a statistically significant difference between the IDH1 mutation detected by RT-PCR and by IHC or radiological methods (p=0.034 and p=0.000, respectively). The sensitivity and specificity of IHC method in detecting IDH1 mutation were 86.6% and 100%, respectively, whereas those of radiological methods were 33.3% and 89%, respectively. CONCLUSION: Conclusively, radiological and IHC methods can be used in cases where RT-PCR cannot be applied for detecting IDH1 mutation. However, the results need to be confirmed by RT-PCR when necessary as these methods may sometimes overlook some IDH-mutant patients.

Giant exophytic tumor of the leg: A case report of amyloidoma with literature review.

Amyloidosis is a heterogeneous group of diseases with the most common form being systemic distribution. The least common type of the disease is tumor formation due to deposition which is called "amyloid tumor (amyloidoma)". Although such tumors can occur in any region of the body, extremity localization is fairly seldom. Here, we report the clinical and histopathological features of amyloidoma in an 81-year-old female patient who presented with a large rapidly growing mass in the left lower extremity.

Pathological findings of the retrospective diagnosis of NIFTP (non-invasive follicular thyroid neoplasm with papillary-like nuclear features) in 84 cases from Turkey and systematic review.

AIM: The terminology of "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) was introduced in 2016; and estimated to cause significant effects in the clinical management of thyroid nodules. The aim of our study is to review our cases that were previously diagnosed as non-invasive encapsulated follicular variant PTC (NI/E-FVPTC) which are compatible with NIFTP and to correlate their follow-up. METHOD: All thyroidectomy cases evaluated in the last 15 years were screened, and possible NIFTP cases were determined among patients with NI/E-FVPTC and they were re-examined microscopically. Revised histopathological criteria were used for the retrospective diagnosis of NIFTP. Histopathological findings were correlated to follow up information. RESULTS: Totally 2138 cases had been previously diagnosed with PTC; 481 (22.5%) of them were FVPTC. After microscopic reevaluation of potential NIFTP cases, 84 cases (3.9%) received final diagnosis of NIFTP. 78.6% of NIFTP patients were female (F/M: 66/18); mean age was 49.0, tumor diameter was 22.7 mm and follow-up time was 66.4 months. 17.9% of NIFTP cases were multifocal and 13.1% were bilateral. No recurrence, lymph node involvement or distant metastasis was detected in any of the patients who were followed up. The mean age of the patients who had total thyroidectomy and received RAI was significantly higher than those who did not. CONCLUSION: Although conservative treatment of NIFTP with lobectomy is recommended, age of the patients has been continuing to be the most important determinant for the clinicians to decide on total thyroidectomy and RAI ablation therapy at our institution.

Calcifying fibrous tumor of the pancreas: A case report.

A calcifying fibrous tumor (CFT) is a rare benign mesenchymal tumor characterized by a hypocellular fibroblastic proliferation with associated chronic inflammation and variably prominent calcification. Gastrointestinal (GI) tract is the most common predilection site of CFT. English-language literature reveals approximate 50 such reports of GI-CFTs. In addition, the most frequently identified sites of the GI tract are stomach, small bowel, and colon. However, CFT has not been reported in the pancreas. In addition, we present the first pancreatic-CFT in this case report.

Solid variant of papillary thyroid carcinoma: An analysis of 28 cases with current literature.

INTRODUCTION: Solid variant papillary thyroid cancer (SVPTC) is a rare variant of papillary thyroid carcinoma (PTC) and its prognostic value is still unclear. Therefore, we re-evaluate the histopathological and clinicopathological features of 28 patients with SVPTC in the light of current literature. MATERIAL-METHODS: Of the 1308 cases were previously diagnosed with PTC and 28 (2,1%) of them which had been diagnosed with SVPTC were re-evaluated retrospectively. RESULTS: Of the 28 patients with SVPTC, 85.7% were female, mean age was 45.18 years and mean tumor diameter was 2.96 cm. Microscopically; tumors had a solid growth pattern amounting to at least 50.0% of the tumor volume. In all cases the tumor cells had characteristic nuclear features of conventional PTC. 11 patients had multifocal tumors, extrathyroidal extension was present in 4 patients and vascular invasion was observed in 7 cases. Regional lymph node metastases were noted in 2 (7.1%) cases at the time of diagnosis. One patient died because of locally advanced disease. Another patient is alive with lung metastases after 48 months from the initial surgery. There was no evidence of local recurrence in other patient. CONCLUSIONS: SVPTC is a rare variant of PTC that should be considered in the differential diagnosis of tumors which show a solid/trabecular growth pattern in the thyroid. It has poor prognostic features such as widespread angioinvasion, extrathyroidal extention, lymph node metastasis, and distant organ metastasis. Multicenter studies involving large number of cases are needed to reveal the prognostic significance of SVPTC, with standardized diagnostic criteria.

High risk of malignancy in cases with atypia of undetermined significance on fine needle aspiration of thyroid nodules even after exclusion of NIFTP.

BACKGROUND: Fine needle aspiration cytopathology (FNAC) is the most reliable tool for evaluating thyroid nodules. However, diagnosing Bethesda category III, atypia/follicular lesion of undetermined significance (AUS/FLUS), is a major limitation. The aim of this study was to evaluate the risk of malignancy (RoM) in AUS/FLUS nodules. A systematic review was also carried out analyzing the largest series. METHODS: Totally 1750 cases (9%) diagnosed with AUS/FLUS were evaluated retrospectively out of 19 392 cases within last 13 years. All patients undergoing surgery for AUS/FLUS were included into the study. Histopathology results were correlated; the impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) diagnosis on RoM is evaluated. RESULTS: Of the 280 patients (16%) undergoing surgery, neoplasia were detected in 177 (RoN:63.2%) and malignancy in 119 (RoM:42.5%) of these neoplasia. Follicular variant of papillary thyroid carcinoma (FVPTC) was the commonest malignancy (55.5%). Additional 58 (20.7%) nodules were neoplastic, of which 26 (9.3%) were encapsulated follicular tumors with unknown malignancy potential (FT-UMP) and 32 (11.4%) were follicular adenomas. The remaining 103 patients (36.8%) had non-neoplastic nodules. After reevaluation of the encapsulated FVPTC cases, 20 of them were NIFTP and RoM dropped to 35.4% with a relative decrease of 16.7% and an absolute decrease of 7.1%. CONCLUSION: In our series, 42.5% of nodules with AUS/FLUS were malignant; 63.2% of them were neoplastic. The RoM and RoN for AUS/FLUS nodules are still much higher than the revised expected RoM of international guidelines even after NIFTP cases excluded. Therefore, current recommendations should be reevaluated periodically in view of detailed clinicopathologic studies.

A Benign Rare Lesion of the Breast: Giant Epidermal Inclusion Cyst.

An epidermal inclusion cyst can be seen at any location. Epidermal cysts are commonly found on the scalp, face, trunk, neck, and extremities. They are rarely seen in the breast parenchyma. These benign lesions are important in that they may undergo neoplastic differentiation, although very rarely. Epidermoid cysts usually develop as a result of the implantation of superficial epidermal tissue into the dermis or subcutaneous tissue after trauma or surgical procedures. In this study, a 37-year-old female patient who underwent a histopathological examination that showed a 10-cm epidermal cyst without a history of trauma or a surgical procedure was discussed.

Fine needle aspiration cytopathology of primary solid adenoid cystic carcinoma of the lung: a case report.

BACKGROUND: Adenoid cystic carcinoma (ACC) is a rare, distinctive salivary gland malignant neoplasm arising infrequently as a primary tumor in the lung. Cytomorphology of lung primary ACC has been rarely reported. To the best of our knowledge, cytopathologic features of the solid type of ACC have not been described as a primary lung tumor. CASE: A case of solid-type primary pulmonary ACC arising in the upper segment of the left mainstem bronchus, suggestively diagnosed cytopathologically by bronchoscope-guided fine needle aspiration (FNA), is presented. Cytopathologic differential diagnoses of ACC with other, more common primary neoplasms of the lung are discussed. FNA smears exhibited a normocellular specimen with several large, densely cellular tissue fragments and individual cells, homogeneous and without prominent atypia. Nuclei were round to oval, with finely granular chromatin. Nucleoli were either absent or inconspicious. The nuclear to cytoplasmic ratio was high. Cytoplasm was minimal; chromatin was bland, with rare chromocenters. There was no nuclear molding. Staining the air-dried smears with May-Grünwald-Giemsa stain revealed metachromatic, magenta material not in spherules or cords but as shapeless structures surrounded by tumor cells. CONCLUSION: A preoperative cytopathologic diagnosis of poorly differentiated primary pulmonary ACC can enhance surgical planning and success of tumor resection.

Serrated Adenoma of Gastric Antrum: Alteration of Mucin Expression Profile and its Role in Carcinogenesis.

Serrated adenomas usually occur in colon, the gastric localization is extremely rare. These polyps have their own carcinogenetic pathway with microsatellite instability. In this report, we present a serrated adenoma localized in gastric antrum with four control endoscopies and biopsies. Immunohistochemical panel of MUC1, MUC2, MUC5AC, and MUC6 was applied to the biopsies. Serrated component, MUC 2 expression increased but goblet cells and MUC5AC expression decreased in follow-up biopsies. This lesion probably was originated from a stem cell that had the potential of differentiation in gastric and intestinal way. This might result an incomplete metaplasia for both colon and stomach. Such lesions which originate from either colon or gastric mucosa may be precancerous and their carcinogenetic pathway may not represent its original organ.

Cystic fluid and fine needle aspiration cytopathology of cystic adult granulosa cell tumor of the ovary: a case report.

BACKGROUND: Fine needle aspiration (FNA) is a valuable tool in the diagnosis of ovarian cysts, especially in the young and when a nonneoplastic cyst is suspected. A case is presented with its cystic fluid, FNA and imprint cytopathology findings diagnosed as cystic adult granulosa cell tumor of the ovary (AGCT). CASE: Cystic fluid and FNA material of a 24-year-old female patient with a left-sided cystic ovarian mass 11.5 cm in diameter was sent intraoperatively for cytopathologic examination. In aspiration cytopathology of AGCT, the presence of regular tumor cells with or without nuclear grooves arranged in a follicular pattern mimicking a Call-Exner body has been regarded as the characteristic cellular feature of the tumor. CONCLUSION: For correct interpretation of the cytopathologic findings, close communication with the clinician performing the aspiration is of vital importance.

Clinicopathologic significance of eosinophilic pleural effusions in a population with a high prevalence of tuberculosis and cancer.

OBJECTIVE: To reveal the diagnostic and prognostic significance of eosinophilic pleural effusions (EPEs) and assess their clinical implications. STUDY DESIGN: Seventy EPEs from 60 patients among 697 consecutive pleural effusions were investigated from 1996-2005 at Kocaeli University Hospital, Kocaeli, Turkey. Koss and Light's criteria were applied in the analysis, which comprised macroscopic, cytopathologic, biochemical and microbiologic examinations. RESULTS: Overall, cancerous underlying conditions were diagnosed in 22 patients (13 malignant and 9 paramalignant), 36.7% of EPEs. Benign causes were found in 43.3% (26 of 60) of the patients. Twelve pleural effusions (20.0%) were idiopathic. The comparison of pleural fluid and peripheral blood findings disclosed no significant difference among the various subgroups. CONCLUSION: EPE could be associated with inflammatory, benign, cancerous and paramalignant conditions. A closer search for a definite causes is warranted in the setting of EPEs, especially in populations with a high prevalence of tuberculosis and malignancy, such as in Kocaeli, Turkey, an industrial city in a developing country.