An assessment of "neuroendocrine differentiation" in malignant melanomas of the sinonasal and oral region.

Mucosal melanomas often require a detailed differential diagnosis and immunochemical study due to their different morphology and pattern characteristics. The tumors may also show fibroblastic, schwannian, smooth muscle, rhabdomyosarcomatous, gangliocytic, epithelial, and neuroendocrine differentiation. All these features can lead to serious diagnostic difficulties. The study aimed to determine the frequency of neuroendocrine differentiation in melanomas of the sinonasal and oral regions and to assess whether there is any relationship between neuroendocrine differentiation and clinical, histopathological, and other immunophenotypic features of this neoplasm. The study included 18 cases diagnosed with oral or sinonasal malignant melanoma. Neuroendocrine differentiation was determined by immunohistochemistry using synaptophysin, chromogranin, CD56, and INSM-1. A cut-off defining neuroendocrine differentiation in malignant melanomas has not been established in the literature. Because of this, any degree of neuroendocrine marker expression was considered as indicative of "neuroendocrine differentiation" without setting any cut-off. Neuroendocrine differentiation was observed in 13 of 18 cases (72.2 %) when a single positive neuroendocrine marker was considered sufficient. The number of cases with at least two positive neuroendocrine markers was 8/18 (44.4 %). Synaptophysin, chromogranin A, CD56, and INSM1 were positive in 33.3 %, 13.3 %, 56.2 %, and 47.1 % of cases, respectively. The results of our study suggest that neuroendocrine differentiation is not uncommon in oral and sinonasal melanomas. Knowing that malignant melanomas can show neuroendocrine differentiation will prevent diagnostic pitfalls.

Which of the fluorine-18 fluorodeoxyglucose positron emission tomography/computerized tomography parameters are better associated with prognostic factors in breast cancer?

The aim of the present study is to evaluate the relationship between the immunohistochemical and histopathological prognostic factors and the metabolic fluorine-18 fluorodeoxyglucose positron emission tomography/computerized tomography (PET/CT) parameters in breast cancer.A total of 94 female patients diagnosed with primary breast cancer (median age: 54.5 years, 94 lesions with size >15 mm) who underwent PET/CT imaging before any treatment were enrolled to this retrospective study. Maximum and average standardized uptake values (SUVmax and SUVavg), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and tumor/liver uptake ratio (TLR) of the primary tumors were calculated and compared between various histopathological and immunohistochemical prognostic factor groups.All metabolic parameters were associated with clinical T stage, metabolic M stage, and nuclear grade. The MTV, TLG, and TLR were significantly higher in patients with suspected lymph node metastasis. There were significant differences according to estrogen receptor and human epidermal growth factor-2 status in the metabolic values other than MTV. In case of progesterone receptor, there were significant differences in the metabolic characteristics except for the MTV and TLG values. The Ki-67 labeling index was moderately correlated with SUVmax, SUVavg, and TLR. All metabolic characteristics except MTV were significantly higher in triple negative breast cancer compared with the other molecular subtypes.The results of the present study suggest that the TLG and TLR values have stronger associations with several prognostic factors in breast cancer (BC) compared with other metabolic parameters.

Bone marrow as a target organ of systemic lupus erythematosus: analysis of cases with myelofibrosis.

AIM: Cytopenia in the course of systemic lupus erythematosus (SLE) may be due to multiple factors. In this study, we aimed primarily to evaluate the detailed results of bone marrow (BM) biopsies of SLE patients, secondly to determine the myelofibrosis (MF) frequency and thirdly to compare BM morphologic findings as well as the clinical and laboratory parameters between groups (with MF and without MF) in cytopenic SLE patients. METHODS: We retrospectively analyzed 224 SLE patients' files. Patients were divided into two groups according to whether they had MF or not. Concurrent SLE organ involvements, medical therapy and detailed BM findings were recorded. RESULTS: Forty-five (20%) of 224 SLE patients were found to have undergone BM biopsy due to cytopenia. Four patients were excluded (two drug-induced cytopenia, one lymphoma, one insufficient BM biopsy samples). While MF was detected in 29 (70.7%) of the 41 patients, 12 patients did not have MF. Between the two groups, no differences were identified in terms Systemic Lupus Erythematosus Disease Activity Index, BM cellularity, or BM dysplastic changes (P = 0.788, P = 0.672 and P = 0.494, respectively). In the SLE-associated MF group, 27 patients responded to immunosuppressive therapy and corticosteroids, but two patients were unresponsive. The response time was longer for the SLE-associated MF group compared to the without MF group (3.3 ± 3.1 months vs. 1.7 ± 1.2 months, P = 0.091). Correlation analysis revealed that increased degree of BM fibrosis delayed the response time (r = 0.471, P = 0.002). CONCLUSIONS: MF is common in SLE patients. SLE-associated MF as an additional factor for cytopenia in SLE patients may lead to delayed response to appropriate therapy, which may be dependent on the increased grade of BM fibrosis.

Retro-orbital, Breast, Cardiac, Skin, and Subcutaneous Metastases of Neuroendocrine Tumor From a Tail Gut Cyst on 68Ga-DOTATATE PET/CT Imaging.

Tail gut cysts are rare congenital lesions developing from postanal primitive gut remnants. They are mostly benign but carry a potential of malignant transformation, such as adenocarcinoma, neuroendocrine tumor, adenosquamous carcinoma, and pseudomyxoma peritonei. We present a 39-year-old woman with a neuroendocrine tumor arising within a tail gut cyst. She underwent complete resection in 2011. After 4 years, she was admitted with breast nodules, left proptosis, and gaze difficulties. Ga-DOTATATE PET/CT demonstrated extensive metastases including pelvic, lymph node, adrenal gland, bone, retro-orbital, cardiac, breast, skin, and subcutaneous metastases.

BCL2, BCL6, IGH, TP53, and MYC protein expression and gene rearrangements as prognostic markers in diffuse large B-cell lymphoma: a study of 44 Turkish patients.

The purpose of this study was to determine the frequency of BCL2, BCL6, IGH, TP53, and MYC protein expression and rearrangements of the respective genes in diffuse large B-cell lymphoma (DLBCL) patients and to assess their prognostic values. Samples from 44 patients with DLBCL were evaluated using fluorescence in situ hybridization and immunohistochemical analyses. BCL6 was the most rearranged gene (63.6%), followed by MYC (31.8%), TP53 (22.7%), and BCL2 (18.2%). Multiple rearrangements were detected in 40.9% of the cases. BCL6 was the most expressed protein (78.6%), followed by TP53 (69.04%), BCL2 (59.5%) and MYC (14.3%). Expression of multiple proteins was detected in 67.4% of the cases. BCL2 (P = .003) expression had a significant negative influence on overall survival,whereas BCL6 (P = .014) expression had a significant positive influence. Our results with a different pattern of gene rearrangements and associated protein overexpression indicate the molecular genetic complexity of DLBCLs, which reflects the morphologic, biologic, and clinical heterogeneity of these lymphomas.

Bone marrow examination in patients with immune thrombocytopenia: is there anything different in older patients?

Immune thrombocytopenia (ITP) is a disorder characterised by immune-mediated accelerated platelet destruction and suppressed platelet production. In the bone marrow examinations of patients with ITP, some investigators found megakaryocyte numbers to be increased while others have found them to be normal. Although recent guidelines recommend against bone marrow examinations in typical ITP patients, the recent introduction of thrombopoietin receptor agonists as an effective treatment for ITP has refocused attention on abnormalities of bone marrow megakaryocytes. In this study, we retrospectively analysed the bone marrow aspiration, flow cytometry-CD45 side scatter (SSC) and biopsy results of our patients with ITP by dividing them into two groups according to age (<60 yr and ≥60 yr). Ninety eight newly diagnosed ITP patients were included in the study. CD45 SSC results were recorded as percentages of normoblasts, granulocytes, lymphocytes, monocytes and myeloid/erythroid ratio. Length of the biopsy specimen, cellularity, presence of dysplasia or fibrosis with number, morphology and distribution of megakaryocytes were recorded. In group 1, there were 49 patients. Mean age was 41.31 ± 12.77 yr. In group 2, there were 49 patients. Mean age was 70.78 ± 7.88 yr. Megakaryocyte numbers on bone marrow aspirates were not recorded in most patients, so we could not comment on this point. Flow cytometry results and bone marrow findings were similar between two groups. In conclusion, there is no difference between bone marrow examinations of young and older patients with ITP, and biopsy should not be recommended in typical ITP patients as already mentioned in guidelines.

Necrotic ulcer: a manifestation of leukemia cutis.

A 71-year-old man presented to our dermatological clinic with a 3-month history of a wound on his leg. He complained of weakness for the past few months. On his dermatological examination he had a 3x3-cm necrotic ulcer on his left tibia (Figure 1). On physical examination, there was 1 x 1-cm axillary lymphadenopathy. There was no other lymph node enlargement, hepatosplenomegaly, or gingival hypertrophy. Peripheral blood results showed 2.4x103/mm3 leukocytes (normal range 4-11 x 103/mm3) with 66% neutrophils. The hemoglobin value was 10.1 g/dL (13-18 g/dL), and the platelet count was 63x103/mm3 (150-440 x 103/mm3). No blasts were detected in a peripheral blood smear. His lactate dehydrogenase level was 567 U/L (240-480 U/L). All other results of blood chemistry were within normal limits. Punch biopsy of the skin lesion showed ulceration and dense dermal acute and chronic inflammation. There was a superficial and deep perivascular and periadnexal infiltrate of neoplastic cells composed of relatively abundant eosinophilic cytoplasm and large nuclei with blastic chromatin and occasional small nucleoli (Figure 2). Mitotic figures were prominent. Immunohistochemical stains were performed, and the neoplastic cells were CD3, CD20, CD138, and S100 protein negative. Myeloperoxidase and CD68 were positive. The histopathological findings were consistent with leukemic infiltration. Examination of bone marrow biopsy revealed that the blastic cells constituted more than 20% of the bone marrow cellularity. Cytogenetic analysis of bone marrow aspiration with fluorescence in situ hybridization was negative for inversion 16, t(8;21) and t(15;7). Histochemical stains for myeloperoxidase, sudan black, periodic acid-Schiff, and alpha naphthyl acetate were also negative. Blastic cells were DR, CD13, CD117, and CD34 positive and CD5, CD7, CD10, CD14, CD19, CD20, CD33, CD41, CD56, CD64, and CD79 negative according to flow cytometry immunophenotyping. Blastic cells were 35% in the bone marrow. Based on the findings of bone marrow examination, the patient was diagnosed as having acute myeloblastic leukeamia (AML) with minimal differentiation (subtype MO) according to French-American-British and World Health Organization classification. The examination of abdominal ultrasonography and thorocic and abominal computed tomography revealed no metastases. The patient was treated with chemotherapy that consisted of cytarabin and daunorubicin. After chemotherapy, the lesion regressed. One month after chemotherapy, the patient presented to the hospital with a complaint of fever. He was diagnosed with febrile neutropenia. He died of cardiac failure 12 months after appearance of skin infiltration.

Autoimmune hypothyroidism and lupus-like syndrome.

The frequency of thyroid disorders, particularly Hashimoto's thyroiditis, may be increased in patients with connective tissue diseases. Both hypothyroidism and connective tissue diseases often cause muscle and joint aches, pains and stiffness. Skin, renal and cardiovascular involvement seen in the course of autoimmune hypothyroidism (AIH) may simulate connective tissue diseases such as systemic lupus erythematosus (SLE). We herein report a case of AIH who presented with massive proteinuria, haematuria, pleural fluid and arthritis simulating SLE.

The effects of intra-rectal and intra-peritoneal application of Origanum onites L. essential oil on 2,4,6-trinitrobenzenesulfonic acid-induced colitis in the rat.

The aim of the present study is to investigate the treatment efficiency of intra-rectal (IR) and intra-peritoneal (IP) application of Origanum onites essential oil (OOEO), which is a well-known antioxidant, in the colitis model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) and ethanol (E) in comparison with dexamethasone therapy through the morphologic damage score. Monoclonal antibodies against intercellular adhesion molecule-1 (ICAM-1, CD54), anti-rat granulocytes, and myeloperoxidase (MPO), were also investigated immunohistochemically. There was a significant difference in terms of ulceration, mucus cell depletion, inflammatory cell infiltration, vascular dilatation (p<0.001), crypt abscesses (p<0.01), and edema (p<0.05) between OOEO-1mg/kg-IR and control colitis groups. A significant difference was encountered in terms of mucus cell depletion, crypt abscesses, inflammatory cell infiltration, vascular dilatation (p<0.01), and ulceration (p<0.05) between the OOEO-0.1mg/kg-IR and control colitis groups. A significant difference was noticed in terms of ulceration, inflammatory cell infiltration, mucus cell depletion (p<0.001), vascular dilatation (p<0.01), and mucosal atrophy (p<0.05) between the OOEO-1mg/kg-IP and control colitis groups. There was a significant difference in terms of ulceration, mucus cell depletion, inflammatory cell infiltration (p<0.001), crypt abscesses, vascular dilatation (p<0.01), and mucosal atrophy (p<0.05) between the OOEO-0.1mg/kg-IP and control colitis groups. No significant difference was determined in terms of ulceration, inflammatory cyst, mucosal atrophy, edema, and vascular dilatation between the dexamethazone and control colitis groups (p>0.05). Under the present conditions, we concluded that IR and IP OOEO treatment, applied at the dosage of 0.1 or 1mg/kg/day, have a significant protective effect on the colonic injury.

Mazabraud's syndrome coexisting with a uterine tumor resembling an ovarian sex cord tumor (UTROSCT): a case report.

The association of intramuscular myxoma and fibrous dysplasia is a rare disease known as Mazabraud's syndrome. We present a case of Mazabraud's syndrome coexisting with a uterine tumor and resembling an ovarian sex cord tumor (UTROSCT). This uterine tumor showed a high mitotic index and cytological atypia. To the best of our knowledge, the coexistence of the two different entities has not been reported in the literature.

A missense mutation in the M1S1 gene found in a turkish patient with gelatinous droplike corneal dystrophy.

PURPOSE: To report a missense mutation in the M1S1 gene found in a Turkish patient with gelatinous droplike corneal dystrophy (GDLD). METHODS: A Turkish patient with GDLD was examined. Keratoplasty was performed and a diagnosis of GDLD was made by histopathologic and electron microscopic studies. Genomic DNA was extracted from peripheral blood and the paraffin-embedded tissue of the corneal button. A 248-bp DNA fragment of the M1S1 gene was amplified, and sequencing reactions were analyzed. The results were compared with those of 30 healthy, nonrelated individuals. RESULTS: On light microscopic examination, sheets of amorphous amyloid deposits were observed in subepithelial regions and in the anterior and midcorneal stroma. Electron microscopy revealed dense collagen fibrils and entrapped filamentous amyloid fibrils in the corneal stroma. A substitution of T-->C at nucleotide 557 was found in the peripheral blood DNA sequence analysis, which resulted in an amino acid substitution of L-->P (L186P). Results were confirmed by direct DNA sequencing analysis of the paraffin-embedded corneal button. The patient with GDLD was homozygous for the mutation, resulting in amino acid substitution L186P. CONCLUSIONS: This is the first report, to our knowledge, of a homozygous mutation (L186P) in the M1S1 gene found in a Turkish patient. The clinical examination may be insufficient in sporadic cases, and histopathologic examination and molecular genetic analysis can accelerate and improve the accuracy of diagnosis in patients with GDLD.

Small cell carcinoma of rectum: a case report.

We present a case of a 40-year-old woman with small-cell carcinoma (SCC) of the rectum. She had profuse bleeding in rectum for 5 d. By colonoscopy, polyps were determined in the rectum and biopsies were carried out. Histopathologically, the polyps were adenomatous. Because of the profuse bleeding in rectum, she underwent low anterior resection. After the diagnosis of SCC, she received intravenous chemotherapy with standard doses of siklofosfamid, adriamycin, and vepesid. Nevertheless, intracranial metastases were revealed and she died 6 mo after the operation.

Chromosomal abnormalities, p53 and Bcl-2 expression and clinical outcome in choroidal melanoma.

OBJECTIVE: To determine whether alterations of p53, Bcl-2 and chromosomes were present in choroidal melanoma and to further characterize the prognosis of these changes. METHODS: The expression of p53 and Bcl-2 protein was assessed by immunohistochemistry from paraffin blocks. Tumours were analysed by comparative genomic hybridization (CGH) to identify chromosomal aberrations. Fifteen tumours were studied, and the survival results were compared by Spearman correlation analysis with a mean follow-up of 36.5+/-8 months. The majority of tumours were mixed (eight cases), and the others were spindle cell (four cases) and epithelioid cell (three cases) types. Four patients have already died due to metastatic disease. RESULTS: p53 was expressed at a low percentage in only two tumours. There were no differences in Bcl-2 expression in our cases. Bcl-2 was expressed by the majority of cells in all cases. Chromosomal copy number aberrations were detected in 10 of the 15 patients by CGH analyses. A gain at chromosome 8 and a loss at chromosome 3 were the most frequently seen abnormalities. The other aberrations observed were losses at 6q, 7q14 and 17p13-15, and gains at 6p and 18q. Two of the three cases with a loss at 17p13 showed a low percentage expression of p53. No relationship was determined between the chromosomal abnormalities, cell type, expression of p53 and survey. The presence of a chromosome 6q deletion in two of the four patients who died of metastatic disease may indicate that chromosome 6q deletion may be correlated with a poor prognosis. CONCLUSIONS: Our results suggest that choroidal melanomas show high levels of chromosomal alterations. Further studies are necessary to determine the correlation between chromosomal abnormalities and prognosis.

Type 1 gastric carcinoid tumor: another extrahepatic manifestation of hepatitis C virus infection?

A 67 year-old female with a 10-year history of cirrhosis due to hepatitis C virus who developed a gastric carcinoid tumor of the corpus is described. Carcinoid tumor was identified during her last routine gastroscopic evaluation for portal hypertension. In the case, serum parietal cell antibodies, hypergastrinemia and atrophic gastritis were also found. Chronic hepatitis C virus infection is known to induce clinical and laboratory signs of autoimmunity. But the question of whether hepatitis C virus plays a pathogenic role in the development of gastric carcinoid tumor is unknown. As far as we know, this is the first report describing gastric carcinoid tumor in hepatitis C virus induced chronic liver disease. We suggest that the possibility of the development of autoimmune atrophic gastritis and carcinoid tumors should be considered in patients with chronic hepatitis C that coexists with autoimmune diseases and has positive parietal cell antibodies.

The effects of sodium phosphate and polyethylene glycol-electrolyte bowel preparation solutions on 2,4,6-trinitrobenzenesulfonic acid-induced colitis in the rat.

The aim of the present study is to evaluate the effects of sodium phosphate (NaP) and polyethylene glycol-electrolyte (PEG-EL) colon cleansing solutions on histopathology of 2,4,6-trinitrobenzene sulfonic acid (TNBS) and ethanol (E)-induced colitis in the rat and normal rat colon. The presence of hyperemia, inflammation and ulcer was evaluated to score of macroscopic morphologic damage. The microscopic criteria including ulceration, mucus cell depletion, crypt abscesses, inflammatory cysts, mucosal atrophy, edema, inflammatory cell infiltration, and vascular dilatation were evaluated to determine the extent of inflammatory reaction. Colitis findings were determined on the rats which were administered TNBS-E. Aphthoid lesions were seen 30% and 20 % of rats, respectively, by NaP and PEG-EL solutions in healthy group. Microscopic examination of aphthoid lesions revealed edema within the lamina propria and lymphoid hyperplasia in the mucosa and submucosa without erosion, ulceration and inflammatory cell infiltration. No significant difference was statistically found either macroscopically or microscopically in terms of the effects of saline, NaP and PEG-EL solutions in healthy rats and rats with colitis (p > .05). Under the present conditions, we concluded administration of NaP and PEG-EL solutions did not cause evident morphological changes on the rectal mucosa macroscopically and microscopically, although in a proportion of rats aphthoid lesions seem as a marker of mucosal damage macroscopically.

Ectopic thyroid in the gallbladder: report of a case.

Ectopic thyroid is a rare developmental anomaly. We describe an unusual case of ectopic thyroid tissue found in the gallbladder wall of a 68-year-old man who underwent cholecystectomy for acute cholecystitis. Pathological findings were compatible with ectopic thyroid tissue in the gallbladder wall. This very rare pathology is discussed with a review of the relevant literature.

Lazaroid attenuates edema by stabilizing ATPase in the traumatized rat brain.

OBJECTIVE: The aim of the present study was to determine the potential therapeutic value of the lazaroid U-83836E on blood brain barrier (BBB) breakdown and edema with respect to the changes in the synaptosomal Na+/K+ and Mg(2+)/Ca(2+)-adenosinetriphosphatase (ATPase) activities, tissue malondialdehyde levels and the neuronal viability in the rat brain subjected to cerebral trauma. METHODS: Traumatic brain injury (TBI) was introduced by applying a 75 gm. cm force to the right parietal cortex using the weight-drop method. The first set of animals was used for determining time course changes of the synaptosomal Na+/K+ and Mg(2+)/Ca(2+)-ATPase and the malondialdehyde levels and were sacrificed 2, 6 and 24h after lesion production. A group of the animals was treated with U-83836E proir to TBI and sacrificed 24h after cerebral injury. A second set of animals was used for evaluating the alterations in BBB disruption and tissue water content and were sacrificed 2, 6 and 24h after lesion production. Two groups of animals were treated with U-83836E and sacrificed after 2 and 24h following TBI. U-83836E was given intraperitoneally thirty minutes before trauma at a dose of 10 mg/kg. Neuronal necrosis was also evaluated in the groups of U-83836E and physiological saline-treated animals. RESULTS: Extravasation of Evans blue into the traumatized hemisphere was maximum at 2h (p<0.001) and returned close to the control levels at 24h after TBI (p>0.05). Edema had developed progressively over time and reached the maximum degree of 2.1% (p<0.001) at 24h. U-83836E showed no effect on the BBB breakdown and the tissue water content at 2h and still had no effect on the BBB breakdown after 24h following the trauma (p>0.05), although it reduced edema after 24h (p<0.01). The losses of Na+/K+ and Mg(2+)/Ca(2+)-ATPase activities were found as 39.5% (p<0.001) and 29.4% (p<0.01) of the control value, respectively, and remained at the decreased levels throughout the experiment. Malondialdehyde level continued to increase over time reaching up to 209% (p<0.001) of the control value 24h after TBI. Both ATPase activities were improved to near control values (p>.05) by the effect of U-83836E. U-83836E inhibited the increase of lipid peroxidation (p<0.001) and also salvaged neuronal necrosis (p<0.05). CONCLUSION: U-83836E given prophylactically after cerebral trauma appears to reduce edema, possibly by inhibiting increases in lipid peroxidation and by stabilizing ATPase. Further studies are recommended to verify the similar effects of the brain penetrating lazaroids when they are given after trauma.

Burned-out tumor of the testis presenting as supraclavicular lymphadenopathy.

Burned-out tumor of the testis is a rare clinical entity. It generally presents with metastases and is nonpalpable in testicular palpation. We present a case of testicular burned-out tumor having supraclavicular and retroperitoneal lymph node metastases. Imaging findings of such tumors have insufficiently been documented in radiology literature. Scrotal sonography is crucial in detecting the regressed tumors especially in patients with extragonadal metastasis of a testicular primary.