MicroRNA expression associated with low-grade cervical intraepithelial neoplasia outcomes.

PURPOSE: Only a fraction of low-grade cervical intraepithelial neoplasia (CIN) progresses to high-grade CIN; however, the biological processes that differentiate progressive CIN from CIN that resolves naturally are poorly understood. MicroRNAs (miRNAs) are important epigenetic regulators of gene expression and thus, miRNA expression profiling can reveal the dysregulated biology underlying disease processes. The purpose of this case-control study was to reveal miRNA expression patterns and predict the underlying biological pathways that are associated with clinical outcomes of low-grade CIN. METHODS: Women with low-grade CIN diagnosis and definitive clinical outcomes (n = 51) were identified retrospectively using electronic clinical records. Comprehensive miRNA expression profiling was performed on the low-grade CIN diagnostic cervical biopsies retrieved from pathology archives. Differential miRNA expression was analyzed by comparing women with CIN that progressed to women with CIN that resolved naturally. RESULTS: Differential expression of 29 miRNAs was observed in low-grade CIN that progressed to high-grade compared to low-grade CIN that resolved. Of these, 24 were significantly downregulated in progressive CIN, including miR-638, miR-3196, miR-4488, and miR-4508, while 5 miRNAs, including miR-1206a, were significantly upregulated. Computational gene ontology analysis based on the discovered miRNAs and their putative mRNA targets revealed biological processes associated with oncogenic phenotypes. CONCLUSION: Distinct miRNA expression profiles are associated with clinical outcomes of low-grade CIN. The functional effects of the differentially expressed miRNAs may be biological determinants of CIN progression or resolution.

Metastatic Papillary Thyroid Cancer to the Liver: The Central Role of a Multidisciplinary Approach to Treatment.

Background: Differentiated thyroid cancer (DTC) is comprised of papillary and follicular subtypes, and both have an overall excellent long-term prognosis. Patients with localized DTC that is successfully treated, usually with surgery, exhibit long-term survival well above 90%. In contrast, patients who develop distant metastatic disease have a significantly worse overall prognosis and outcome, often with disease that is refractory to conventional therapy such as surgery, radioactive iodine, and hormone suppression. For patients who recur with distant metastatic disease, limited effective treatment options are available, and most die of their disease within 5 years of recurrence. Case Report: We report the case of a 26-year-old female who presented with recurrent papillary thyroid cancer and a metastatic lesion isolated to the liver. Because of the extremely large size of the metastatic liver mass upon initial presentation, we took a neoadjuvant, multifaceted approach to treatment that included selective internal radioembolization therapy, an oral multikinase inhibitor, and surgical resection of the tumor mass after maximal reduction in tumor size. However, the patient died of metastatic DTC after 39 months of treatment. Conclusion: A multimodal, comprehensive approach to managing such complex patients is essential to optimize both the sequence and therapeutic approach to treatment.

Pathology Image of the Month:Cough and Shortness of Breath in a Noncompliant Patient with HIV/AIDS.

A 37- year-old man with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) was admitted to the intensive care unit following a four month history of progressive shortness of breath, productive cough, and flu-like symptoms. His HIV/AIDS was diagnosed at the age of 19 (CD4 count =15; viral load = 294,436 copies/ mL) and was complicated by hemodialysis-dependent, HIV-associated nephropathy, prior Pneumocystis pneumonia and known noncompliance with prescribed antiretroviral therapy. Chest film at admission was interpreted as diffuse bilateral interstitial and airspace opacities with a right sided layering density representative of laminar pleural effusion. Bacterial blood cultures were subsequently negative. A bronchoalveolar lavage was performed and an image from the cytologic cell block is seen above in Figure 1. The patient's respiratory status continued to deteriorate and he was converted to comfort care. Following death, an unlimited autopsy examination was requested by the family and authorized by the coroner. At autopsy, additional gross pathologic findings included 350ml of chylous appearing pleural fluid and serous ascites (700ml). Histopathology revealed intra-alveolar acute fibrinopurulent exudate, chronic pericarditis and end-stage nephropathy. Similar cells to those shown above in Figure 1 were identified in lung epithelium and in pancreatic acinar cells. Special stain for Pneumocystis was negative.

Primary clear cell adenocarcinoma of the colon: a case report and review.

A case of primary clear cell adenocarcinoma of the colon, a rare oncologic variant, was diagnosed in a 25-year-old man who presented with partial bowel obstruction. To understand better the pathology of this neoplasm, a retrospective review of Entrez PubMed entries describing primary clear cell adenocarcinoma of the colon and/or rectum was performed. Only 13 previous cases of primary clear cell adenocarcinoma of the colon and/or rectum have been reported, with an average presentation age of 57 years and generally afflicting the descending colon of men. Herein we present a case occurring in the distal ascending colon of the youngest patient in the literature to date. Our patient's diagnosis is rare in occurrence, location, and age of onset.

Follicular and papillary carcinoma: a thyroid collision tumor.

The objective of this study was to report a collision tumor of papillary and follicular carcinoma of the thyroid. Case report and review of the literature was studied. A 62 year old female presented with a thyroid mass diagnosed the year prior. Physical exam revealed a 6 × 4 cm predominantly left sided thyroid mass that was confirmed on imaging as well. Thyroid function tests were within normal limits. Ultrasound-guided fine needle aspiration suggested a follicular neoplasm. Consequently, the patient underwent a left hemi-thyroidectomy. The pathology was reported as being collision tumor with a combination of follicular and papillary carcinoma. A completion thyroidectomy was performed followed by post operative radio-iodine therapy. Collision tumors are rare involving two or more histologically distinct neoplastic morphologies separated by normal tissue in one or more organ systems. This is to our knowledge the first report of a collision tumor of the thyroid involving a follicular and papillary carcinoma.

A 52-year-old woman with headache and bradycardia.

Cardiac sarcoidosis should be suspected in young patients with cardiac symptoms, especially when there is concurrent personal or family history of sarcoidosis. While sarcoidosis is self-limiting in about 40% of cases, cardiac involvement portends a more ominous prognosis with higher mortality rates. The definitive diagnostic test for cardiac sarcoidosis is the endomyocardial biopsy, an invasive test with low sensitivity. The multiple clinical modalities, which comprise the Japanese Ministry of Health clinical diagnostic guidelines, and newer modalities, including MRI, are more sensitive and demonstrate reliable diagnostic efficacy when compared to endomyocardial biopsy. Management of cardiac sarcoidosis involves early initiation of corticosteroid therapy to limit progression and maintain the structural and electrical integrity of the heart. When necessary, more invasive modalities (e.g. ICD, pacemaker, and transplant) may improve outcomes in advanced disease.

COL1A1-PDGFB fusion in a pediatric Bednar tumor with 2 copies of a der(22)t(17;22).

We present a 10-year-old girl with a pure Bednar tumor (pigmented dermatofibrosarcoma protuberans) of the right shoulder. Cytogenetic analysis demonstrated 47 chromosomes with 2 copies of a derivative chromosome 22, der(22)t(17;22)(q22;q13). Fluorescence in situ hybridization (FISH) analysis demonstrated the COL1A1-PDGFB fusion on both der(22) chromosomes. By RT-PCR and sequencing, we observed a fusion of the COL1A1 exon 41 with PDGFB exon 2. This pure pediatric Bednar tumor in a child, like childhood dermatofibrosarcoma protuberans, had a linear structural abnormality rather than a ring chromosome that is more commonly encountered in adult Bednar and dermatofibrosarcoma protuberans tumors. The underlying molecular abnormality in this pediatric Bednar tumor is the same as in dermatofibrosarcoma protuberans.