Involuting luteinized thecoma of the ovary.

Spontaneous tumor involution in ovarian stromal tumors is a poorly understood phenomenon. In this report, we describe a rare case of luteinized thecoma that showed extensive involutional changes, such that cellular elements diagnostic of luteinized thecoma were sparse. The convoluted contour of the tumor resembled that observed in a corpus albicans; however, the neoplasm was considerably larger, and the contents of the nodule differed from that of a corpus albicans. The diagnosis of luteinized thecoma was established by the identification of residual aggregates of neoplastic theca cells and a nodule of lutein cells that were positive for inhibin and steroidogenic factor-1. Features of involution within the tumor included a few theca and lutein cells with pyknotic nuclei and abundant cytoplasmic lipid, occasional large adipocytes among the lutein cells, extensive hyalinization, dystrophic calcification, a myxohyaline nodule, and adipose metaplasia. It is likely that some of the aforementioned changes are the result of accompanying ischemia. Cleaved caspase-3 staining patterns were negative within residual lutein and theca cells; thus, we were unable to establish the occurrence of apoptotic bodies.

Cystic tumor of the atrioventricular node: an unexpected finding in an explanted heart.

SUMMARY: We report herein a unique case of cystic tumor of atrioventricular (AV) node (CTAVN), which, to our knowledge, is the first of its kind diagnosed in an explanted heart specimen and only the fourth diagnosed antemortem. Often, this rare tumor can only be diagnosed by careful gross examination and adequate sampling of AV node region. It is an important differential diagnosis in young patients with syncopal attacks and varying degrees of heart blocks. CONTEXT: CTAVN is a rare, benign tumor. Most cases have been reported in young females (mean age, 38 years). Patients typically present with conduction abnormalities including complete heart block leading to sudden cardiac death. Most cases have been identified at autopsy; no cases to our knowledge have been reported in an explanted heart. DESIGN: A 19 year-old female presented to the cardiac transplant clinic for evaluation of severe congestive heart failure felt to be secondary to postpartum cardiomyopathy. The patient's history was significant for congenital heart block requiring placement of a permanent pacemaker at 12 years of age. At the time of this presentation, electrocardiogram revealed second-degree AV block, and two-dimensional echocardiogram showed lipomatous hypertrophy of the interatrial septum. Seven months later, orthotopic cardiac transplantation was performed. RESULTS: On gross examination, the explanted heart weighed 500 g and had biventricular dilatation. Histologic sections of left and right ventricle revealed myocyte hypertrophy and interstitial fibrosis consistent with dilated cardiomyopathy. Sections from the AV node showed a lesion with morphological features of CTAVN. It was composed of cysts of varying sizes lined by transitional, cuboidal and squamous epithelium. Some cysts were filled with proteinaceous debris that were periodic acid Schiff-positive and diastase resistant. CONCLUSIONS: CTAVN occurs exclusively in the area of the AV node, tricuspid valve, and inferior atrial septum. These lesions are now believed to be endodermal in origin, although mesothelial origin was earlier proposed. We report herein a case of CTAVN, the first of its kind diagnosed in an explanted heart specimen and only the fourth diagnosed antemortem.

The CD117 immunohistochemistry tissue microarray survey for quality assurance and interlaboratory comparison: a College of American Pathologists Cell Markers Committee Study.

CONTEXT: We have developed tissue microarray-based surveys to allow laboratories to compare their performance in staining predictive immunohistochemical markers, including proto-oncogene CD117 (c-kit), which is characteristically expressed in gastrointestinal stromal tumors (GISTs). GISTs exhibit activating mutations in the c-kit proto-oncogene, which render them amenable to treatment with imatinib mesylate. Consequently, correct identification of c-Kit expression is important for the diagnosis and treatment of GISTs. OBJECTIVE: To analyze CD117 immunohistochemical staining performance by a large number of clinical laboratories. DESIGN: A mechanical device was used to construct tissue microarrays consisting of 3 x 1-mm cores of 10 tumor samples, which can be used to generate hundreds of tissue sections from the arrayed cases, suitable for large-scale interlaboratory comparison of immunohistochemical staining. RESULTS: An initial survey of 63 laboratories and a second survey of 90 laboratories, performed in 2004 and 2005, exhibited >81% concordance for 7 of 10 cores, including all 4 GIST cases, which were immunoreactive for CD117 with >95% staining concordance. Three of the cores achieved less than 81% concordance of results, possibly due to the presence of foci of necrosis in one core and CD117-positive mast cells in 2 cores of CD117-negative neoplasms. CONCLUSIONS: There was good performance among a large number of laboratories performing CD117 immunohistochemical staining, with consistently higher concordance of results for CD117-positive GIST cases than for nonimmunoreactive cases. Tissue microarrays for CD117 and other predictive markers should be useful for interlaboratory comparisons, quality assurance, and education of participants regarding staining nuances such as the expression of CKIT by nonneoplastic mast cells.

E-cadherin status in breast cancer correlates with histologic type but does not correlate with established prognostic parameters.

Our objective was to assess the loss of E-cadherin (EC) as a diagnostic marker or a predictor of prognosis. We stained 276 breast carcinomas with monoclonal antibodies to EC (invasive lobular carcinomas [ILC] and variants, 59; invasive ductal carcinoma and ductal special types [IDC], 204; tubulolobular carcinoma [TLC], 4; and invasive carcinoma [IC], uncertain whether lobular or ductal type, 9). The results were as follows: EC+IDCs, 99.5%; EC-ILCs, 90%; EC+ILCs, 10%; EC+pleomorphic ILCs, 20%; EC-ICs, 44%. All 4 TLCs showed positive tubules while cords were negative. Statistically a correlation of EC loss with a positive diagnosis of ILC was found but there was no correlation with any prognostic tumor variables. A negative EC stain confirms the diagnosis of ILC (specificity, 97.7%; negative predictive value, 96.8%; sensitivity, 88.1%; positive predictive value, 91.2%). EC is helpful in classifying cases with indeterminate histologic features. EC loss is uncommon in nonlobular carcinomas with no correlation to currently established prognostic variables.

Use of microsatellite analysis in detection of tumor lineage as a cause of death in a liver transplant patient.

Malignant tumors are a significant cause of long-term morbidity and mortality in allograft recipients. Most solid tumors in transplant recipients are assumed to arise de novo in the setting of chronic immunosuppressive therapy; however, there have been instances in which malignant tumors have been transplanted in donated tissue from apparently healthy donors. We report a case of a 49-year-old liver transplant patient who presented with metastatic melanoma 9 months after transplantation for hepatocellular carcinoma and who later succumbed to the disease. To investigate the possibility that melanoma was derived from the donor liver, we used a commercially available polymerase chain reaction-based microsatellite marker assay to perform tissue identity testing. The genetic profiles of the patient's original hepatocellular carcinoma and the melanoma from the autopsy specimen were compared with the profile of the normal donor liver tissue, which was still available for testing. The pattern of microsatellite allelic expression strongly suggested that the melanoma detected at autopsy originated from the transplanted liver.

Chronic abdominal pain caused by heterotopic ossification with functioning bone marrow: a case report and review of the literature.

Heterotopic ossification is rarely seen after midline abdominal surgery. The etiology of heterotopic ossification is unknown. Although it is well recognized that heterotopic ossification may contain osteogenic cells and/or hematopoietic cells, to our knowledge, no case has ever been reported to have histologic evidence of hematopoiesis. We report the occurrence of heterotopic bone with bone marrow showing normal trilineage hematopoiesis in the incision scar of a woman who underwent gastric reduction surgery for the treatment of obesity. The literature regarding heterotopic ossification and extramedullary hematopoiesis is reviewed in this report, and discussion focuses on the mechanism of this pathophysiologic process.

Solitary sclerotic fibroma of skin: a possible link with pleomorphic fibroma with immunophenotypic expression for O13 (CD99) and CD34.

BACKGROUND: Solitary sclerotic fibroma (SF) presents as a well circumscribed dermal nodule, composed of sparse spindle cells with alternating wavy collagen fibers arranged in a storiform pattern. The histogenesis and nature of this histologically distinct lesion are uncertain. Whether this peculiar tumor represents a true hamartoma or a degenerating end of various fibrous lesions such as pleomorphic fibroma (PF), dermatofibroma, or angiofibroma is still controversial. High proliferating index of spindle cells in SF argues against the possibility of being a degenerating end product of another lesion. METHODS: We studied morphological features and immunoprofile of eight SFs, in comparison with four PFs, one collagenized dermatofibroma, two angiofibromas, and two periungual fibromas. Immunostains for CD34, CD31, O13 (CD99), Factor XIIIa, S-100, CD68 (KP-1), and MIB-1 were carried out using a labeled streptavidin-biotin method with DAKO-automated immunostainer. Paraffin blocks of two SFs were reprocessed for electron microscopic studies. Clinical data of all patients with SF were also reviewed. RESULTS: Spindle cells and pleomorphic cells in SF and PF showed diffuse immunoreactivity for CD34 and O13 but were negative for CD31, S-100, and CD68. Spindle cells in one dermatofibroma and one angiofibroma were positive for Factor XIIIa. Proliferating index (MIB-1) was very low in all cases of SF, contradicting some previous reports. CONCLUSIONS: SF is a fibrotic lesion with cells positive for CD34 and O13. It shares a common immunoprofile with PF but is distinct from dermatofibroma and other common spindle cell lesions of skin. O13 expression in SF has not been previously described.

Diagnostic value of HMB-45 and anti-Melan A staining of sentinel lymph nodes with isolated positive cells.

Numerous immunohistochemical stains have been employed to detect metastatic melanoma in sentinel lymph node (SLN) biopsies. HMB-45 is considered by some as a specific tool to detect early metastatic melanoma (1). Occasionally, one or two isolated HMB-45-positive cells may cause complications in diagnostic interpretation. The goal of this study was to evaluate the reliability of HMB-45 staining of SLNs with sparse isolated positive cells and to compare its staining with anti-Melan A antibody. HMB-45 and anti-Melan A antibody immunostaining was performed on (Group A) 15 histologically negative SLNs excised from patients with malignant melanoma (MM) and on (Group B) 15 histologically negative SLNs excised from patients with breast carcinoma (BC). None of the patients had clinical evidence of systemic metastasis at the time of SLN biopsy. Five cutaneous biopsies with changes of postinflammatory hyperpigmentation (PIHP) were also stained with both antibodies. HMB-45 staining was repeated in all Group B SLNs after blocking endogenous biotins. Electron-microscopic studies were performed on all cases of PIHP. Isolated HMB-45-stained cells were present in 6 of 15 SLNs removed for MM; 8 of 15 for BC; and 3 of 5 cutaneous biopsies of PIHP. HMB-45 reactivity persisted after blocking endogenous biotins in 6 of 8 positive SLNs from Group B. Anti-Melan A antibody was negative in all SLNs of group A and B and in dermal melanophages of all five cases of PIHP. HMB-45 positivity was demonstrated in histologically negative SLNs and cutaneous biopsies, especially in the milieu of aggregated melanophages. Phagocytosis of premelanosomes by macrophages in the draining lymph nodes may account for isolated cell positivity and can hinder correct diagnostic interpretation. HMB-45 may not be a reliable marker for the detection of micro-metastasis of MM and requires correlation with other immunohistochemical markers, such as anti-Melan A antibody, to enhance specificity.