Iatrogenic Kaposi Sarcoma Precipitated by Anti-Tumor Necrosis Factor-Alpha (Anti-TNF-α) Therapy.

Kaposi sarcoma (KS) is a vascular neoplasm caused by human gammaherpesvirus 8 (HHV-8). Four subtypes of KS are described: classic (Mediterranean), epidemic (acquired immunodeficiency syndrome (AIDS)-associated), endemic (sub-Saharan Africa), and iatrogenic. Iatrogenic KS due to tumor necrosis factor-alpha (TNF-α) inhibitor therapy is particularly rare. A 66-year-old female with a history of seropositive rheumatoid arthritis (RA) presented with a skin lesion on her right second toe. Diagnosed with RA four years prior, she failed to respond to methotrexate, hydroxychloroquine, and etanercept. As a result, she was started on adalimumab. Approximately two months into therapy, she presented to the emergency room with a dark brown skin lesion on her right second toe. She underwent excisional biopsy of the mass, which demonstrated a tumor composed of spindle cells forming slit-like spaces with extravasated red blood cells. The tumor was positive for cluster of differentiation 31 (CD31), CD34, and HHV-8 immunostains and negative for smooth muscle antibody (SMA) and desmin immunostains, consistent with Kaposi sarcoma. Human immunodeficiency virus (HIV) serology was negative. The patient was diagnosed with iatrogenic KS. Adalimumab was discontinued. The patient was started on alitretinoin and underwent adjuvant radiation therapy to minimize recurrence. TNF-α is a pro-inflammatory cytokine that has been implicated in many inflammatory diseases and in cell apoptosis. While anti-TNF-α agents have improved outcomes in many immune-mediated diseases, higher rates of infections and malignancy have also been reported. The incidence of KS with anti-TNF-α therapy remains a rare entity. Therefore, it is extremely important for patients receiving biologic agents, including TNF-α inhibitors, to have a close follow-up and receive routine skin evaluation for malignancy. Clinicians should have a high index of suspicion for KS in such non-HIV patients started on immunosuppressive agents.

Synchronous colon cancer with pulmonary metastasis and follicular variant of papillary thyroid cancer metastasising to kidney.

Thyroid malignancies are one of the fastest growing cancers in the world, with the majority being papillary thyroid cancer. Follicular variant of papillary thyroid cancer accounts for about 10%-20% of papillary thyroid carcinomas. The usual sites for metastases of these tumours are lungs and bones with renal metastases being extremely rare. We describe a case of a 64-year-old woman who presented with abdominal pain. On subsequent imaging, she was found to have a colonic mass with metastatic lesions in the lungs and tumour involving left kidney. On biopsy and immunohistochemical staining, the renal mass showed positivity for thyroid cancer markers. Thyroid scan was noted to be negative and the patient was placed on active surveillance after undergoing chemotherapy for colonic adenocarcinoma.

Nucleometric study of anisonucleosis, diabetes and oxidative damage in liver biopsies of orthotopic liver transplant recipients with chronic hepatitis C virus infection.

Anisonucleosis is defined as a morphological manifestation of nuclear injury characterized by variation in the size of the cell nuclei. It has been described in variety of benign conditions and is most pronounced in dysplasia and malignancy. To better understand the pathogenesis of anisonucleosis in liver diseases, this study focused on hepatocyte anisonucleosis in biopsies of liver transplant recipients who developed recurrent chronic hepatitis C virus (HCV) infection. Post transplant surveillance liver biopsy specimens were evaluated employing light microscopy, immunohistochemistry, digital image analysis, and nucleometry for histopathological analyses, measurement of nuclear size, and quantification of tissue expression of oxidative marker 8-hydroxy-2'deoxyguanosine (8-OHdG). Our aim in this study was to determine whether there were any independent associations between hepatocyte anisonucleosis and various clinicopathological parameters. These features included patient age, body mass index, gender, race, donor age, live versus cadaveric donor status, history of diabetes mellitus, history of tacrolimus and cyclosporine therapy, duration post transplant and parameters of hepatitis activity index, fibrosis index, steatosis, and oxidative tissue damage in formalin fixed paraffin embedded (FFPE) liver biopsies as determined by immunohistochemistry using 8-OHdG, an indicator of hydroxyl radical mediated tissue damage. Our findings suggested that in liver transplant recipients with recurrent chronic HCV infection, hepatocyte anisonucleosis is more pronounced in individuals with diabetes mellitus (p = 0.0016), and among those who have heightened hepatic expression of the oxidative damage marker 8-OHdG (p = 0.0053). Further studies are necessary to determine whether anisonucleosis is an independent marker for diabetes or oxidative damage.

Hashimoto encephalopathy with fulminant myocarditis.

There are very limited data concerning the association of lymphocytic thyroiditis with cardiomyopathy, and there is only one published report of fatal cardiomyopathy associated with autoimmune thyroiditis. An association of Hashimoto encephalopathy (HE) with autoimmune myocarditis has not yet been reported. Here we describe a case of a 31-year-old man with autoimmune thyroiditis complicated by HE, who succumbed to autoimmune myocarditis. This association raises the possibility that HE and myocarditis may share a common pathogenetic mechanism in some cases.

Validity of sampling error as a cause of noncorrelation.

BACKGROUND: Sampling error is a common explanation of noncorrelation in women whose Papanicolaou (Pap) tests show high-grade intraepithelial lesions (HSIL) but whose follow-up cervical biopsies show only cervical intraepithelial neoplasia (CIN) 1, koilocytosis, or reactive/inflammatory changes. The purpose of this study was to demonstrate the validity of sampling error in this setting by determining the proportion of negative colposcopic cervical biopsies in women with HSIL who subsequently undergo cone/loop electrode excision procedure (LEEP) biopsies or repeat cervical biopsies that confirm the diagnosis of high-grade CIN (HGCIN). METHODS: In all, 368 cases of HSIL were retrieved from the computerized database from January 1, 2003 to December 31, 2005. Follow-up was obtained as part of routine quality assurance/quality control activities including cytologic-histologic correlation. RESULTS: A total of 368 HSIL Pap diagnoses were retrieved. Of the 254 cases that were followed up by cervical biopsy, 146 showed HGCIN in the biopsy. Of the remaining 108 patients whose cervical biopsies failed to demonstrate HGCIN, 47 had a subsequent procedure, either cone/LEEP, cervical biopsy, or repeat Pap test. Cone biopsy/LEEP was performed in 34 cases (72.3%) with a diagnosis of HGCIN in 19. Repeat cervical biopsy was performed in 9 cases (19.1%) with HGCIN diagnosed in 5. Repeat Pap test was performed in 4 cases (8.5%) with HSIL diagnosed in 2. CONCLUSIONS: In the population of women with HSIL by Pap test followed up by cervical biopsy with or without subsequent cone/LEEP, there was a discordant cervical biopsy rate for HGCIN of 43%. In the subgroup of women with HSIL by Pap test followed up by cervical biopsy and subsequent cone/LEEP or repeat cervical biopsy, the proportion of women with negative colposcopic cervical biopsy and subsequent histology-proven HGCIN was 56%. These figures justify sampling error as a valid cause of noncorrelation in women with HSIL followed up by cervical biopsy alone.