Keratoacanthoma and squamous cell carcinoma are distinct from a molecular perspective.

Keratoacanthoma is a controversial entity. Some consider keratoacanthoma as a variant of squamous cell carcinoma, whereas others see it as a distinct self-resolving squamoproliferative lesion. Our objective is to examine the relationship of keratoacanthoma with squamous cell carcinoma and normal skin by using DNA microarrays. DNA microarray studies were performed on formalin-fixed and paraffin-embedded blocks from ten cases of actinic keratoacanthoma utilizing the U133plus2.0 array. These results were compared with our previously developed microarray database of ten squamous cell carcinoma and ten normal skin samples. Keratoacanthoma demonstrated 1449 differentially expressed genes in comparison with squamous cell carcinoma (>5-fold change: P<0.01) with 908 genes upregulated and 541 genes downregulated. Keratoacanthoma showed 2435 differentially expressed genes in comparison with normal skin (>5-fold change: P<0.01) with 1085 genes upregulated and 1350 genes downregulated. The most upregulated genes, comparing keratoacanthoma with normal skin included MALAT1, S100A8, CDR1, TPM4, and CALM1. The most downregulated genes included SCGB2A2, DCD, THRSP, ADIPOQ, adiponectin, and ADH1B. The molecular biological pathway analysis comparing keratoacanthoma with normal skin showed that cellular development, cellular growth and proliferation, cell death/apoptosis, and cell cycle pathways are prominently involved in the pathogenesis of keratoacanthoma. The most enriched canonical pathways were clathrin-mediated endocytosis signaling, molecular mechanisms of cancer and integrin signaling. The distinctive gene expression profile of keratoacanthoma reveals that it is molecularly distinct from squamous cell carcinoma. The molecular pathways and genes differentially expressed in comparing keratoacanthoma with normal skin suggest that keratoacanthoma is a neoplasm that can regress due to upregulation of the cell death/apoptosis pathway.

A Rare Case of a Pilar Cyst With Ductal Differentiation.

Pilar cysts are common squamous-lined cysts that typically occur on the scalp. They are believed to arise from the isthmus of anagen hairs or from the sac surrounding catagen and telogen hairs. The authors describe a rare case of a pilar cyst with prominent ductal differentiation, presumably of eccrine derivation. Sweat duct differentiation has been described in a myriad of cutaneous neoplasms and rarely within epidermoid cysts. The authors could only find one other case in the literature describing a pilar cyst with sebaceous and apocrine differentiation. The clinicopathologic findings are described here.

Melanocytic matricoma with melanocytic atypia: report of a unique case and review of the literature.

Melanocytic matricoma is a rare cutaneous neoplasm of presumed anagen hair follicle origin with approximately 10 reported cases in the literature. Melanocytic matricomas are clinically and histopathologically distinct cutaneous nodular proliferations of matrical and supramatrical cells admixed with dendritic melanocytes, which typically occur in the sun-exposed areas of elderly patients. We report a new case with additional histopathologic features not previously described. An 82-year-old white man presented with an exophytic papule of the ear clinically suspicious for basal cell carcinoma. Histopathologic examination demonstrated a polypoid neoplasm consisting of an admixture of matrical and shadow cells with numerous interspersed dendritic and epithelioid melanocytes arranged singly and in large expansile nests. An unusual feature in this case included prominent melanocytic proliferation with associated nuclear atypia and increased mitotic activity. Although atypical and malignant melanocytic colonization has been reported in basal cell carcinomas and squamoproliferative lesions, to our knowledge, it has not been previously described in melanocytic matricomas. The biologic significance of atypical melanocytic proliferations within melanocytic matricomas is uncertain and requires further study of additional cases and long-term follow-up.

Focal nodular hyperplasia after orthotopic liver transplantation.

Focal nodular hyperplasia (FNH) has been well characterized in native livers, but to our knowledge, no cases of FNH have been described in liver allografts. We review the clinicopathological features of 6 FNHs identified in 4 patients after orthotopic liver transplantation. There were 3 male patients and 1 female patient ranging in age from 2 to 63 years. The time from transplant to a diagnosis of FNH ranged from 15 to 118 months. Two patients presented with an incidental solitary liver nodule. One patient presented with 2 liver nodules, and the other patient initially presented with 1 liver nodule and was found to have another nodule at autopsy 6 years later. Two FNHs were seen as an incidental finding at autopsy, and the other 4 were initially identified on ultrasound. Follow-up magnetic resonance imaging and computed tomography scans revealed features atypical for FNH and suspicious for hepatocellular carcinoma. The initial diagnosis of FNH was made by needle core biopsy in 3 cases and at autopsy in 2 cases. The lesions ranged in size from 1.7 to 6.9 cm. Three patients had conditions associated with altered hepatic vascular perfusion; 2 patients had portal vein thrombosis, and 1 had a partial allograft from a living donor. In conclusion, FNH can present as a hepatic nodule after orthotopic liver transplantation and should not be confused with hepatocellular carcinoma. Because of altered hepatic circulation in the posttransplant liver, a diagnosis of FNH would not be unexpected. FNH should be considered in the differential diagnosis of hepatic nodules within the posttransplant liver, especially in patients with known hepatic vascular perfusion abnormalities.

Mucinous adenocarcinomas of the thymus: report of 2 cases and review of the literature.

BACKGROUND: Most adenocarcinomas of the mediastinum are metastatic lesions. Primary thymic adenocarcinomas are extremely rare neoplasms. We could find only 12 cases reported in the literature; of these 12, only 4 were of the mucinous subtype. DESIGN: We report 2 additional cases of the mucinous subtype, including a previously unreported mucinous variant with numerous psammoma bodies. RESULTS: The first case in a 61-year-old woman resembled a mucinous (colloid) carcinoma of other organs such as the breast and colon. It consisted of islands and strips of tumor cells floating in large pools of extracellular mucin. A unique feature of this tumor was the presence of numerous psammoma bodies. Immunohistochemically, the tumor cells were positive for cytokeratin (CK) 7 and negative for CD5. The second case in an 82-year-old woman was a mucinous adenocarcinoma arising from a thymic cyst with areas of transition from benign to dysplastic epithelium. The tumor cells formed dilated glands, cords, and small nests that infiltrated the thymic cyst wall and exhibited evidence of mucin production. Immunohistochemically, the tumor cells were positive for CK 7 and focally positive for both CD5 and CK 5/6. CONCLUSIONS: Mucinous adenocarcinoma, with or without, psammoma bodies, may be of primary thymic origin and should be considered in the differential diagnosis of malignant mediastinal tumors. These 2 cases provide further documentation of the rare occurrence of primary mucinous adenocarcinomas of the thymic gland.

Molecularly enriched pathways and differentially expressed genes distinguishing cutaneous squamous cell carcinoma from pseudoepitheliomatous hyperplasia.

INTRODUCTION: Cutaneous squamous cell carcinoma (SCC) is one of the most commonly diagnosed nonmelanoma skin cancers. Occasionally, the diagnosis can be challenging as there are many simulating preneoplastic and reactive squamous lesions. One of the most difficult lesions to differentiate from SCC is pseudoepitheliomatous hyperplasia (PEH). The objective of our study is to differentiate cutaneous SCC from PEH using gene expression microarrays and examine the enriched molecular pathways and genes. DESIGN: DNA microarray studies were performed on formalin-fixed and paraffin-embedded blocks of the skin: 10 cases of SCCs and 10 cases of PEHs using the U133 plus 2.0 array. RESULTS: A total of 703 differentially expressed genes were identified between SCCs and PEHs (>2-fold change, P<0.05) including multiple upregulated S100 calcium-binding proteins and downregulated homeobox genes. Functional analysis of these genes suggests that oxidative phosphorylation, mitochondrial dysfunction and the polyamine regulation pathways are involved in the pathogenesis of SCC. CONCLUSIONS: The distinctive gene expression profile of SCC and PEH offers the ability to use DNA microarrays to distinguish between them by an objective molecular measure. The molecular pathways and differentially expressed genes provide an insight into the pathogenesis of SCCs and may serve as future targets for therapeutic intervention.

Has the 2004 revision of the International Society of Heart and Lung Transplantation grading system improved the reproducibility of the diagnosis and grading of cardiac transplant rejection?

We compared the interobserver reproducibility of the 1990 and 2004 International Society for Heart and Lung Transplantation (ISHLT) grading system for cardiac rejection. The 2004 ISHLT grading system for cardiac allograft rejection did not improve reproducibility partly due to pathologists' disagreement in diagnosing Grades 1B/1R and 3A/2R rejection. To achieve better reproducibility, better criteria for defining 1B/1R vs. 3A/2R rejection and markers of myocyte injury are needed.

Recurrent hepatic lymphangiomatosis after orthotopic liver transplantation.

Hepatic lymphangiomatosis is a rare disease characterized by an abnormal lymphatic proliferation involving the liver alone, liver and spleen, or multiple organs. Hepatic lymphangiomatosis becomes symptomatic secondary to compression or replacement of the normal parenchyma, which can lead to liver failure. Resection and orthotopic liver transplantation (OLT) can be used as treatment for this disease. We herein describe a 42-year-old female who had undergone successful OLT for hepatic lymphangiomatosis with recurrent disease detected 19 yr later in the transplanted liver. This is, to our knowledge, the first described case of recurrent hepatic lymphangiomatosis after OLT. In conclusion, we discuss the clinical, radiologic, pathologic, and immunohistochemical findings and review other reported cases of hepatic lymphangiomatosis that have undergone OLT.