Multiple fibrotic lung nodules in a patient with primary Sjögren's syndrome.

Evaluation of bilateral lung nodules noted on imaging poses a diagnostic challenge to clinicians as it can have many differentials from benign to malignant causes. It becomes especially critical to identify them right when there are underlying autoimmune conditions and risk factors for infection. However, a thorough investigation can lead to the recognition of rare associations as described below. We present here a 57-year-old woman who was admitted to the hospital with shortness of breath. Imaging with a computed tomography (CT) scan showed that she had 8 bilateral cystic pulmonary nodules with focal areas of ground-glass opacity and mediastinal lymphadenopathy. Fibrobronchoscopy and histopathological studies were done on the right middle lobe lung nodule demonstrated that the lung nodule was fibrotic with reactive inflammation but showed no malignant cells. Upon further detailed history and chart review, it was noted that the patient had a history of dry eyes leading to an autoimmune workup showing positive antinuclear antibodies (ANA), anti-Ro, and anti-La antibodies with no follow-up since then. This lead to the suspicion that these nodules could be related to underlying Sjögren's syndrome. Initial inpatient management with intravenous steroids showed significant improvement in her symptomatology. Hence, we present this rare association of lung nodules with Sjögren's syndrome and its management for awareness of this condition.

A Rare Case of Pure Primary Large Cell Neuroendocrine Carcinoma of the Gallbladder.

Primary large cell neuroendocrine carcinoma (LCNEC) of the gallbladder is a rare malignancy which is often associated with non-LCNEC histologic components. Histologically "pure" LCNECs of the gallbladder are exceedingly rare with only 15 cases reported in the medical literature. Clinically, LCNECs present with abdominal pain and jaundice and follow an aggressive course with patients surviving a median of 15 months following initial diagnosis. To our knowledge, we present the 16th case of a histologically pure LCNEC in a 62-year-old African American male who was successfully treated surgically. After discharge, he was subsequently lost to follow-up. Due to the extreme rarity of such disease entity, accurate diagnosis and proper management are essential for the best clinical outcome.

Primary Pulmonary Leiomyosarcoma in a Forty-Year-Old Woman.

Primary pulmonary leiomyosarcomas (PPLs) are rare aggressive malignancies originating from the smooth muscle cells of the pulmonary interstitium, bronchial tree, or blood vessels. Accounting for <0.5% of lung tumors, PPLs are often initially undetected or misdiagnosed as pulmonary emboli, cardiac neoplasms, or as other more common lung cancer subtypes. Due to their aggressive and often lethal clinical profile, the diagnostic delay of PPL can significantly affect patient outcomes and must be avoided. Here we describe a case of PPL in a 40-year-old woman.

Ethylmalonic Encephalopathy 1 Protein Is Increased in Colorectal Adenocarcinoma.

BACKGROUND/AIM: Ethylmalonic encephalopathy 1 protein (ETHE1) plays an important role in sulfide catabolism and polysulfide formation. As sulfides and polysulfides have recently been identified as playing important roles in cancer, we hypothesized that ETHE1 expression would be increased in colon cancer. MATERIALS AND METHODS: We used tissue microarray analysis to compare ETHE1 expression in benign colonic epithelium compared to colonic adenocarcinoma. In total, 26 benign colonic epithelial samples were compared to 122 cases of colonic adenocarcinomas. RESULTS: Compared to benign colonic epithelium, ETHE1 expression was significantly increased (~two-fold) in colonic adenocarcinoma. Additionally, this expression increased with increasing colon cancer tumor grades. CONCLUSION: ETHE1 expression is increased in colon cancer compared to benign colonic epithelium. These data, combined with previous studies, suggest that ETHE1 may contribute to colon carcinogenesis by promoting tumor cell bioenergetics and polysulfide formation.

Cystathionine Gamma-Lyase Is Increased in Testicular Seminomas, Embryonal, and Yolk Sac Tumors.

BACKGROUND: Testicular cancer constitutes 1.0% of male cancer and typically carries a good prognosis. As far as we are aware, the role for hydrogen sulfide in testicular cancer and the level of hydrogen sulfide-synthesizing enzyme have never been addressed. Here we examined cystathionine gamma-lyase (CSE) expression in several germ-cell testicular tumors. MATERIALS AND METHODS: Tissue microarrays were employed to examine CSE expression in 32 benign testicular samples, 88 testicular seminomas, 34 embryonal carcinomas, 4 mature teratomas, and 16 yolk sac tumors, and CSE expression was compared to that seen in benign testicular tissue. RESULTS: Compared to benign testicular tissue, CSE expression was increased in all three types of testicular neoplasm but not in mature teratomas. Highest CSE expression was identified in embryonal carcinomas, which often show a relatively aggressive clinical course. CONCLUSION: For the first time, we show that CSE is increased in several common testicular germ-cell tumor types.

Hydrogen sulfide and DNA repair.

Recent evidence has revealed that exposing cells to exogenous H 2 S or inhibiting cellular H 2 S synthesis can modulate cell cycle checkpoints, DNA damage and repair, and the expression of proteins involved in the maintenance of genomic stability, all suggesting that H 2 S plays an important role in the DNA damage response (DDR). Here we review the role of H 2 S in the DRR and maintenance of genomic stability. Treatment of various cell types with pharmacologic H 2 S donors or cellular H 2 S synthesis inhibitors modulate the G 1 checkpoint, inhibition of DNA synthesis, and cause p21, and p53 induction. Moreover, in some cell models H 2 S exposure induces PARP-1 and g-H2AX foci formation, increases PCNA, CHK2, Ku70, Ku80, and DNA polymerase-d protein expression, and maintains mitochondrial genomic stability. Our group has also revealed that H 2 S bioavailability and the ATR kinase regulate each other with ATR inhibition lowering cellular H 2 S concentrations, whereas intracellular H 2 S concentrations regulate ATR kinase activity via ATR serine 435 phosphorylation. In summary, these findings have many implications for the DDR, for cancer chemotherapy, and fundamental biochemical metabolic pathways involving H 2 S.

Focal Segmental Glomerulosclerosis Preceding Type 2 Papillary Renal Cell Carcinoma.

Renal cell carcinoma (RCC) is the predominant renal malignancy in adults. Of the four general subtypes, papillary renal cell carcinoma (P-RCC) is the second most common and can be subdivided into type I, type II, and a mixture of type I and II. Focal segmental glomerulosclerosis (FSGS) is the most common glomerulopathy at all ages, and it can be seen as a paraneoplastic syndrome. RCC, in general, is known to present with many paraneoplastic syndromes, and glomerulopathies are among these. Rarely, RCC and glomerulopathies may overlap in the same patient. Here, we report a 58-year-old male with a past medical history of FSGS and chronic kidney disease (CKD), stage III, who was found to have an incidental renal mass that was later diagnosed as type II P-RCC. The histology showed pseudostratified tumor cells with an eosinophilic cytoplasm that formed papillary configurations and displayed areas of necrosis. The prior FSGS diagnosis exhibited segmental sclerosis, refractory tufts, and capillary membrane wrinkling. A period of 1.5 years elapsed between the diagnosis of the glomerulopathy and the malignancy. The tumor was found to be at stage TIb. To our knowledge, this may be the first reported case of usual-type FSGS as paraneoplastic glomerulopathy (PG) preceding P-RCC. Because FSGS only sparingly affects the kidney and is a common glomerulopathy in adults, it is reasonable to complete comprehensive diagnostic studies and commence medically necessary treatment, especially in the background of other renal comorbidities. These preexisting comorbidities may be associated with malignancy very early in its course. The probability of RCC-associated paraneoplastic glomerulopathy is low, which means an already incidentally found renal mass may conceal a serpentine paraneoplastic syndrome. A more developed understanding of these manifestations can lead experienced clinicians to suspect and possibly uncover an insidious RCC before it advances.

Histopathologic Study of Pathergy Test in Behçet's Disease.

BACKGROUND: The pathergy test (PT) is important in the diagnosis of Behçet's disease (BD). However, misinterpretation of the test might cause false-positive or false-negative results. Therefore, immunopathologic and histopathologic tests are recommended with PT. AIMS AND OBJECTIVES: The aim of this study is to determine histopathologic findings of positive pathergy reaction at BD. MATERIALS AND METHODS: This study was performed on 23 patients with BD. All patients were in active period of the disease. After 48 h from the injection, biopsy was performed on positive pathergy lesions. RESULTS: Of the specimen from positive PT lesions of patients with BD, nine revealed mixed type inflammatory cell infiltration (39.1%), two revealed lobular panniculitis without vasculitis (8.7%), two revealed neutrophil rich infiltration (8.7%), and five revealed lymphocyte rich infiltration (21.7%) at the subcutaneous tissue. Mixed type inflammatory cell infiltration (43.4%), endothelial swelling and thickening (17.3%), erythrocyte extravasation (26.0%), perivascular cell infiltration (13.0%), lymphocytic vascular reaction (8.6%), lymphocytic vasculitis (13.0%), and leukocytoclastic vasculitis (21.7%) were detected in dermis by histopathologic examinations. There was no statistically significant difference between histopathologic findings and sex, family history, and systemic involvement except uveitis. CONCLUSION: This is an exceptional study since it is the first study that determines subcutaneous tissue findings of positive pathergy reaction in Behçet patients. In our study, uveitis was found to be statistically significant in the patients who had vasculitis in dermis. It can be a clue for prediction of disease severity and course. Further, studies that include wide number of patients will better illuminate the correlation between subcutaneous tissue findings and disease severity and clinical course.

Serum levels of natriuretic peptides in patients with Behcet's disease.

The objective of our study was to elucidate serum levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) in Behcet's disease (BD) patients with active and inactive period. The multicenter study included 53 patients with active (n = 28) and inactive (n = 25) BD (mean age, 34.3 +/- 9 years; 15 men and 38 women) satisfying the International Study Group criteria and 26 healthy controls (mean age, 34.4 +/- 6.1 years; seven men and 19 women) matched for age and gender from a similar ethnic background. Serum natriuretic peptides levels were determined by enzyme immunoassay kit. Mean serum ANP concentrations in the active patients (4.01 +/- 1.21 ng/ml) were significantly lower than in the healthy controls (5.76 +/- 1.99 ng/ml, p = 0.004). Mean serum BNP levels were found to be significantly higher in both the active (6.19 +/- 2.97 ng/ml) and inactive (6.49 +/- 2.88 ng/ml) BD groups compared with the control group (3.82 +/- 1.1 ng/ml, p = 0.004 and p = 0.001, respectively). Mean serum CNP concentrations in the active patients (0.49 +/- 0.12 ng/ml) were significantly lower than in the inactive patients (0.65 +/- 0.2 ng/ml, p = 0.017) and the healthy controls (0.8 +/- 0.27 ng/ml, p < 0.001). Our results suggest that changes in natriuretic peptide levels may be associated with vasculitis that play role in the etiopathogenesis of the BD.