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Biomedical subjects

J Rosai

Publications and source records attributed to J Rosai.

At least 91 records · Page 5Linked to original sources

Detection of the SYT-SSX chimeric RNA of synovial sarcoma in paraffin-embedded tissue and its application in problematic cases.

We report the development of a reverse-transcriptase polymerase chain reaction assay that detects (in paraffin-embedded, formalin-fixed tissue) the SYT-SSXchimeric RNA transcript resulting from the t(X;18) of synovial sarcoma. The primers chosen detect both of the SSX1 and SSX2 partners, and the target sequence is small enough (87 base pairs) to be reliably detected in archival and variably processed consultation material. To demonstrate its usefulness, we applied it to 14 problematic cases, including spindle cell tumors of the thoracic region, of the neck, and of subcutaneous tissue. For instance, we show that, depending on the location, synovial sarcoma can mimic malignant solitary fibrous tumor, the spindle epithelial tumor with thymus-like differentiation, or skin adnexal tumors. Molecular detection of the SYT-SSX chimeric RNA should allow the reclassification of difficult cases in which the morphologic features overlap different entities or in which tumor nosology is still evolving.

Adult↗

Follicular dendritic cell tumor: review of the entity.

Malignant neoplasms showing follicular dendritic cell differentiation are uncommon. Most reported cases have involved lymph nodes of the neck, mediastinum, and axilla. Approximately 30% of the cases were located in extranodal sites, such as liver, tonsil, and intra-abdominal soft tissue. Microscopically, follicular dendritic cell tumor is composed of oval to spindle cells with eosinophilic cytoplasm arranged in sheets, fascicles, and whorls, sometimes admixed with foci showing a storiform pattern of growth. The tumor cells are characteristically admixed with small lymphocytes. The tumor nuclei are oval to spindle, with thin nuclear membranes, small basophilic nucleoli, and clear or dispersed chromatin. Scattered multinucleated tumor cells are frequently seen. Necrosis, marked cellular atypia, high mitotic rate, and abnormal mitoses may occur and are harbingers of an aggressive behavior. The tumor cells typically express CD21, CD35, Ki-M4p, Ki-FDRC1p, and vimentin, with occasional positivity for S-100 protein, muscle-specific actin, and epithelial membrane antigen. Ultrastructural examination shows complex interdigitating cytoplasmic processes joined by desmosomes. The behavior of these tumors is more akin to that of a low-grade soft tissue sarcoma than a malignant lymphoma and is characterized by local recurrences in 36% of cases and metastases in 28%. A small proportion of cases have arisen against a background of Castleman disease of the hyaline-vascular type and others in association with Epstein-Barr virus infection. Complete surgical resection is the treatment of choice whenever feasible. Adjuvant radiotherapy or chemotherapy appears indicated in cases having adverse pathological features and in recurrent or incompletely resected lesions. Much still needs to be learned about the most effective adjuvant therapy and the molecular biology of these tumors.

Burkitt Lymphoma↗

Bcl-2 and Bax expression in thyroid tumours. An immunohistochemical and western blot analysis.

Bcl-2 and Bax proteins, which are involved in repressing and promoting programmed cell death, respectively, have been investigated immunohistochemically and by Western blot analysis in a series of thyroid tumours. Three immunostaining patterns were identified. Benign lesions and well-differentiated thyroid carcinomas displayed a profile similar to that of normal follicular epithelium, in which Bcl-2 immunostaining was predominant. Thyroid carcinomas associated with an aggressive behaviour, such as the tall-cell variant of papillary carcinoma and the poorly differentiated carcinomas, co-expressed both proteins. Finally, anaplastic carcinomas expressed only the Bax protein. Western blot analyses revealed that the anti-Bcl-2 antibody recognized two bands, of molecular weights 21 kDa and 25 kDa. This was only seen in the tall-cell papillary carcinomas and in the anaplastic carcinomas.

Adult↗

Abnormal intracellular and extracellular distribution of basement membrane material in papillary carcinoma and hyalinizing trabecular tumors of the thyroid: implication for deregulation of secretory pathways.

Papillary carcinoma (PC) and hyalinizing trabecular tumors (HTT) of the thyroid share several morphological features, including the presence of nuclear pseudoinclusions (NPI). One of the distinct characteristics of HTT is its hyalinizing stroma, which contains abundant basement membrane (BM) material. We investigated the distribution of BM material in PC and HTT. Fifteen cases of PC and nine cases of HTT were analyzed immunohistochemically with monoclonal antibodies for type IV collagen and laminin. Three stromal staining patterns were observed: (1) linear staining along the epithelium lining papillae, between trabeculae, and around follicles; (2) focal absence of staining; (3) lumpy or diffuse stromal staining. Although the latter was more commonly seen in HTT, all three patterns were present in both tumor types. More interestingly, we observed two hitherto undescribed intracellular staining patterns in both tumor types: intracytoplasmic dotlike staining and staining of NPI. Electron microscopy was performed in three cases of PC. Dilated cisternae of endoplasmic reticulum containing dense amorphous material resembling BM were observed in the cytoplasm in one case and in the NPI in another. These findings suggest the presence of a common pathway for the abnormal production of BM in both PC and HTT. Two mechanisms that may account for the abnormal intracellular detection of BM materials are proposed: (1) intracellular invagination/phagocytosis of extracellular matrix by the tumor cells; (2) abnormal production or alteration in secretory pathway in tumor cells resulting in intracellular accumulation and intranuclear invagination. The combination of immunohistochemical and electron microscopic findings favors the latter. The similar patterns of BM deposition shared by PC and HTT further support the hypothesis that PC and HTT are related to each other.

Basement Membrane↗

Transcontinental consults in surgical pathology via the Internet.

An efficient and inexpensive electronic system to submit surgical pathology cases in consultation via the Internet is presented. A transcontinental pilot study showed a high degree of concordance between the diagnosis provided by the consultant on the basis of the pathology images and that given after examining the corresponding microscopic slides.

Adult↗

Prognostic significance of detection of prostate-specific antigen transcripts in the peripheral blood of patients with metastatic androgen-independent prostatic carcinoma.

OBJECTIVES: To evaluate the prognostic significance of reverse transcriptase polymerase chain reaction (RT PCR) detection of prostate-specific antigen (PSA) mRNA in relation to survival in patients with metastatic androgen-independent prostatic carcinoma (AIPC). METHODS: Peripheral blood from 122 men (64 from Memorial Sloan-Kettering Cancer Center [MSKCC] and 58 from the Dana Farber Cancer Institute [DFCI]) with metastatic (Stage D2) AIPC was analyzed for PSA mRNA using RT PCR. Forty-one controls without prostatic carcinoma were also evaluated. RESULTS: RT PCR positivity for PSA mRNA was present in 24 of the 64 (38%) patients seen at MSKCC and in 26 of the 58 (45%) patients followed at DFCI. All control individuals were PSA PCR negative. There was a significant correlation between RT PCR positivity and decreased survival in each of the Memorial and Dana Farber population (P = 0.028 and 0.039, respectively). Serum PSA (at time of blood collection for PCR) was not predictive of survival as a continuous variable in the MSKCC [P = 0.31] and the DFCI (P = 0.09) groups. RT PCR for PSA mRNA was found to be independent from and superior to serum PSA in predicting survival in both the MSKCC and DFCI populations (P = 0.048 and P = 0.027, respectively). CONCLUSIONS: The detection of PSA mRNA in the peripheral blood by RT PCR is a predictor of survival in patients with metastatic AIPC, and PCR is superior to a single serum PSA measurement. Further studies are needed to test the value of this factor in comparison to and coupled with other prognostic parameters.

Adult↗

Thymic neuroblastoma in adults: report of three cases with special emphasis on its association with the syndrome of inappropriate secretion of antidiuretic hormone.

We report three cases of neuroblastoma arising within the thymus of elderly patients. All tumors consisted of primitive neuroblasts showing focal gangliocytic differentiation within nests of neuropil. All stained for neuroendocrine markers but were negative for cytokeratins and for the MIC2 gene product. One tumor was associated with the syndrome of inappropriate secretion of antidiuretic hormone, an endocrinopathy we found in three of five case reports of thymic neuroblastoma in adults. Immunohistochemical stains confirmed production of antidiuretic hormone by this tumor. One patient died of progressive disease, one patient is disease free at 18 months, and the other patient died of unrelated causes, a spectrum that reflects the variable clinical behavior others have reported. The possible histogenesis of these purely neural tumors includes malignant transformation of a mediastinal teratoma, aberrantly located sympathetic ganglia, neuroectodermal cells native to the normal thymus, and precursors of thymic epithelial cells that have differentiated along neural lines.

Aged↗

Cytogenetic analysis of subcutaneous angiolipoma: further evidence supporting its difference from ordinary pure lipomas: a report of the CHAMP Study Group.

Subcutaneous angiolipomas are benign soft-tissue lesions consisting of two mesenchymal elements (i.e., adipose tissue and blood vessels) and having distinct clinical features. They usually are multiple, with an obvious male predominance, and hereditary occurrence has been described. Twenty subcutaneous angiolipomas from 10 patients with typical clinical and morphologic features were reviewed. All lesions had a normal karyotype. This finding is in striking contrast with ordinary lipomas, spindle-cell and pleomorphic lipomas, lipoblastomas, and hibernomas, most of which have characteristic clonal chromosomal aberrations. The normal karyotype of subcutaneous angiolipoma as well as its distinct clinical and morphologic features suggest a different pathogenesis from pure lipomas.

Adult↗

Breast involvement by extranodal Rosai-Dorfman disease: report of seven cases.

Seven cases of breast involvement by extranodal Rosai-Dorfman disease are presented. The patients were women and their ages ranged from 15 to 84 years. Three patients had disease confined to the breast; one had involvement of the breast and ipsilateral axillary lymph nodes, and two had bilateral breast involvement as well as disseminated systemic disease. In all cases the clinical and radiographic presentation of the breast lesion raised the possibility of a malignant tumor. All but one of the lesions were treated by excisional biopsy. Microscopically, the lesions were relatively circumscribed, often multinodular masses, located in the breast stroma, with or without associated involvement of the subcutaneous tissue and dermis. They were composed of sheets of S-100 protein-positive large histiocytes displaying lymphocytophagocytosis, scattered in a polymorphous background of mature lymphocytes and plasma cells. The microscopic differential diagnosis includes idiopathic granulomatous mastitis, infective granulomas, Langerhans' cell histiocytosis, Erdheim-Chester disease, fibrous histiocytoma, and malignant melanoma.

Adolescent↗

Thyroid paraganglioma: a clinicopathologic and immunohistochemical study of three cases.

We report three cases of intrathyroidal paraganglioma. The patients were adult women without significant personal or family histories that presented with an asymptomatic thyroid nodule. The tumors were single, well-circumscribed solid masses, 2 cm in greatest diameter, located within one thyroid lobe. Microscopically, they were encapsulated and showed the typical nesting (Zellballen) pattern of paraganglioma in other sites. Two of the tumors were composed of small- to medium-sized cells with granular amphophilic cytoplasm, and the third consisted of relatively large cells having a similar staining quality. Immunohistochemically, all tumors showed positivity for neuron-specific enolase, chromogranin A, and synaptophysin. S-100 protein-positive sustentacular cells were demonstrated in each case. Negative staining for epithelial markers, thyroglobulin, carcinoembryonic antigen, calcitonin, calcitonin gene-related peptide, serotonin, vimentin, and Congo red excluded other tumors that were considered in the differential diagnosis, such as medullary carcinoma, hyalinizing trabecular adenoma, atypical follicular adenoma, Hurthle-cell neoplasm, and metastatic carcinoid tumor. The patients were alive and well without evidence of recurrent disease at the time of the last follow-up. The previous literature on these tumors is discussed. We conclude that intrathyroidal paraganglioma exists and that this tumor can be distinguished from other similar-appearing neoplasms in this organ.

Biomarkers, Tumor↗

Metastatic neuroendocrine tumors to the thyroid gland mimicking medullary carcinoma: a pathologic and immunohistochemical study of six cases.

The clinical, pathological, and immunohistochemical features of six cases of metastatic neuroendocrine and carcinoid tumors to the thyroid simulating medullary thyroid carcinoma (MTC) are described. The patients were women between the ages of 24 and 70 years who, without symptoms or significant past medical histories, presented with either a single mass or multiple thyroid nodules. The primary source of the tumor was only discovered on follow-up. Two of the neoplasms were classical carcinoid tumors, one was a carcinoid predominantly composed of large cells, another showed a prominent oval to spindle cell component, and the two remaining cases were atypical carcinoid/high-grade neuroendocrine carcinomas. The immunohistochemical profile was inconsistent with MTC in that all tumors were negative for calcitonin and only two were focally positive for carcinoembryonic antigen (CEA). A variable pattern of staining for other neuroendocrine and epithelial markers was obtained in each case. Despite the morphologic and immunohistochemical similarities with MTC, the diagnosis of a metastatic neuroendocrine tumor to the thyroid should be favored in the presence of a predominantly interstitial pattern of spread; occurrence of multiple tumor foci; folliculotropism; rosette formations with lumen and cuticular borders; and lack of immunoreactivity for calcitonin and CEA. The differential diagnosis between MTC and metastatic neuroendocrine carcinoma to the thyroid is of importance because of the vast differences in treatment and prognosis.

Adult↗

Lymphocyte-rich well-differentiated liposarcoma: report of nine cases.

Nine well-differentiated liposarcomas with foci simulating the appearance of malignant lymphoma and other lymphoid disorders are reported. Their clinical presentation and evolution were not significantly different from those of their conventional counterparts lacking a lymphoid infiltrate. Microscopically, these tumors were characterized by areas of ordinary well-differentiated liposarcoma, admixed with discrete nodules comprised of small germinal centers, and separated by an admixture of lymphocytes, spindled stromal cells, collagen, and blood vessels, in which highly atypical tumor cells were embedded. The differential diagnosis included Hodgkin's disease, Castleman's disease, and inflammatory pseudotumor. Immunohistochemical evaluation revealed a pre-dominance of T cells in the lymphocytic population. Molecular genetic studies revealed no evidence of clonal rearrangement of the T cell receptor gene, supporting the interpretation of these lymphocytes as reactive. Awareness of the existence of this variant of inflammatory liposarcoma should prevent its misinterpretation as a primary lymphoproliferative process.

Adult↗

Duplication of chromosome segment 12q15-24 is associated with atypical lipomatous tumors: a report of the CHAMP collaborative study group. CHromosomes And MorPhology.

Ordinary lipomas are cytogenetically characterized by a variety of balanced rearrangements involving chromosome segment 12ql3-15, and atypical lipomatous tumors (ALT) by supernumerary ring chromosomes or giant markers known to contain amplified 12q sequences. In a series of 228 cytogenetically analyzed and histopathologically reexamined ordinary lipomas and ALT, 10 tumors showed unbalanced chromosome-12 aberrations. All 4 tumors with loss of segments from 12q were classified as ordinary lipomas, whereas 5 of the 6 tumors showing gain of 12q material were diagnosed as ALT. One or three extra copies of 12q15-q24 were present in all 5 ALT. We conclude that duplication of 12q sequences may be a sufficient level of amplification for development of the microscopic appearance that characterizes ALT.

Chromosome Aberrations↗

Polymerase chain reaction in the detection of micrometastases and circulating tumor cells.

BACKGROUND: The sensitive detection of circulating tumor cells and micrometastases may have important therapeutic and prognostic implications. METHODS: The molecular detection of occult tumor cells can be accomplished by amplifying tumor specific abnormalities present in the DNA or mRNA of malignant cells with the polymerase chain reaction (PCR). This approach has been used mainly for hemato-lymphoid malignancies. The other main PCR strategy for the detection of minimal residual disease (MRD) involves amplification of tissue-specific mRNA. This method was applied for the detection of occult disease in solid tumors. RESULTS: PCR was shown to be superior to conventional techniques in detecting circulating tumor cells and micrometastases allowing the identification of 1 tumor cell diluted with 10(6)-10(7) normal cells. The central question of whether PCR positivity reliably predicts relapse remains unanswered for many tumor types. Serial analysis of a large number of samples is needed and currently undertaken in many institutions. CONCLUSIONS: PCR is a highly sensitive method for the detection of circulating tumor cells and micrometastases in solid and hematopoietic malignancies. If PCR positivity is found to be a reliable tool, this will likely have a major impact on the treatment of many cancers. Patients could be selected for systemic therapy at an earlier stage when the metastatic tumor burden is low. PCR may improve the preoperative staging of patients with epithelial malignancies and therefore help avoid unnecessary radical procedures. Furthermore, this test may be useful in monitoring the effectiveness of adjuvant therapy, the intensity and duration of which is tailored to the individual patient. The impact of this PCR based approach on clinical oncology is likely to be profound.

Breast Neoplasms↗

Desmoid fibromatosis is a clonal process.

Desmoid fibromatosis is a locally aggressive proliferative soft tissue lesion of controversial nature. The authors investigated the clonality of this process by molecular genetic analysis of DNA methylation pattern at a polymorphic site at the human androgen-receptor gene (HUMARA) to examine the inactivation pattern of the X chromosome. Twenty desmoid fibromatoses including primary and recurrent lesions from 11 female patients were studied. Sixteen lesions from eight patients showed nonrandom X inactivation, consistent with a clonal origin and, therefore, a true neoplastic nature. Furthermore, multiple recurrent lesions from two patients exhibited the same inactivation pattern as the corresponding primary lesions, suggesting that they were derived from the same cell clone as the primary lesion. One patient was homozygous at the HUMARA locus, and two patients had the same skewed pattern in their normal and lesional tissues. The authors also found that digestion with HpaII, but not HhaI, failed to generate a nonrandom X inactivation pattern in some of the cases, suggesting that the methylation status at the HpaII sites was altered in some lesions, and that HhaI should be used to verify results and to avoid incorrect conclusions.

Adolescent↗