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Biomedical subjects

Saul Suster

Publications and source records attributed to Saul Suster.

At least 19 recordsLinked to original sources
PubMed2007

Pilot study of rosiglitazone therapy in women with breast cancer: effects of short-term therapy on tumor tissue and serum markers.

PURPOSE: Peroxisome proliferator-activated receptor gamma (PPARgamma) is a steroid nuclear receptor that is activated by natural compounds such as specific fatty acids and synthetic drugs such as thiazolidinedione antidiabetic agents. Expressed in normal and malignant mammary epithelial cells, activation of PPARgamma is associated with antiproliferative effects on human breast cancer cells in preclinical studies. The purpose of this study was to test the hypothesis that PPARgamma ligand therapy might inhibit tumor growth and progression in human breast cancer. EXPERIMENTAL DESIGN: We conducted a pilot trial of short-term (2-6 weeks) treatment with the thiazolidinedione rosiglitazone in 38 women with early-stage (T(is)-T(2), N(0-1), M(0)) breast cancer, administered between the time of diagnostic biopsy and definitive surgery. RESULTS: Short-term treatment with rosiglitazone (8 mg/d) did not elicit significant effects on breast tumor cell proliferation using Ki67 expression as a measure of cell proliferation and surrogate marker of tumor growth and progression. In pretreatment tumors notable for nuclear expression of PPARgamma by immunohistochemistry, down-regulation of nuclear PPARgamma expression occurred following rosiglitazone administration (P = 0.005). No PPARG mutations were identified, and the incidence of P12A and H446H polymorphisms did not differ relative to U.S. controls (P = 0.5). Treatment with rosiglitazone resulted in increased serum adiponectin (P < 0.001), decreased insulin levels (P = 0.005), and increased insulin sensitivity (P = 0.004). Rosiglitazone was well tolerated without serious adverse events. CONCLUSION: Our data indicate that short-term rosiglitazone therapy in early-stage breast cancer patients leads to local and systemic effects on PPARgamma signaling that may be relevant to breast cancer.

Adult↗
PubMed2006

Myxopapillary ependymoma of the posterior mediastinum.

A left paravertebral mass discovered incidentally on routine examination in a 39-year-old woman is described. Computerized tomography studies revealed a 7 x 6 cm, well circumscribed, noncalcified soft tissue mass with lobular borders abutting the left inferior pulmonary vein and descending aorta. It was not possible to determine the exact anatomic location of the mass based on the imaging studies as both peripheral lung tumors and posterior mediastinal lesions may exhibit the imaging findings described here. At thoracotomy, the mass was seen to be well circumscribed, focally attached to the pleura but without involvement of lung parenchyma, and situated in the left posterior mediastinum. On histological examination, the lesion showed the classical features of myxopapillary ependymoma. Immunohistochemical studies confirmed this impression by demonstrating strong positivity of the tumor cells for S-100 protein, glial fibrillary acidic protein, and CD99 and negative staining with other differentiation markers. A review of the literature with a discussion of the histologic and radiologic differential diagnosis of these lesions is presented.

12E7 Antigen↗
PubMed2006

The Toker tumor: spectrum of morphologic features in primary neuroendocrine carcinomas of the skin (Merkel cell carcinoma).

Primary neuroendocrine carcinoma of the skin is a relatively rare tumor that was first described by Cyril Toker in 1972. Since the seminal paper by Toker based on simple morphologic observations and detailed clinical correlation, our understanding of the clinical, morphological, and biological attributes of these lesions has grown exponentially with their increased awareness by pathologists and clinicians as well as with the many contributions of modern diagnostic techniques. The present review focuses principally on the various morphologic appearance that these tumors are able to adopt, the role of modern special techniques for diagnosis, and the conditions that need to be considered in their differential diagnosis.

Aged↗
PubMed2006

High-grade urothelial carcinoma of the renal pelvis: clinicopathologic study of 108 cases with emphasis on unusual morphologic variants.

A clinicopathologic study of 108 cases of high-grade urothelial carcinomas of the renal pelvis is presented. Of the 108 tumors, 44 (40%) showed unusual morphologic features, including micropapillary areas (four cases), lymphoepithelioma-like carcinoma (two cases), sarcomatoid carcinoma (eight cases, including pseudoangiosarcomatous type), squamous differentiation and squamous cell carcinoma (15 cases), clear cells (two cases), glandular differentiation (two cases), rhabdoid, signet-ring or plasmacytoid cells (four cases), pseudosarcomatous stromal changes (four cases) and intratubular extension into the renal pelvis (three cases). Pathological staging was available in 62 patients; of these, 46 cases (74%) were in high stage (pT2-pT4) and 16 (26%) were in low stage (pTis, pTa, pT1). Clinical follow-up ranging from 1 to 256 months (median: 50 months) was available in 42 patients; of these, 26 (61%) died of tumor with a median survival of 31 months. The patients who did not die of their tumors showed only minimal or focal infiltration of the renal parenchyma by urothelial carcinoma, whereas those who died of their tumors showed massive infiltration of the kidney by the tumor. High-grade urothelial carcinomas of the renal pelvis can show a broad spectrum of histologic features similar to those seen in the urinary bladder. Our results support the finding that, unlike urothelial carcinomas of the bladder, the majority of primary urothelial carcinomas of the renal pelvis are of high histologic grade and present in advanced stages. Our study further highlights the fact that, in the renal pelvis, urothelial carcinomas show a tendency to frequently display unusual morphologic features and metaplastic phenomena. The importance of recognizing these morphologic variants of urothelial carcinoma in the renal pelvis is to avoid confusion with other conditions. The possibility of a high-grade urothelial carcinoma should always be considered in the evaluation of a tumor displaying unusual morphologic features in the renal pelvis, and attention to proper sampling as well as the use of immunohistochemical stains will be of importance to arrive at the correct diagnosis.

Adult↗
PubMed2006

Differential expression of smooth muscle myosin, smooth muscle actin, h-caldesmon, and calponin in the diagnosis of myofibroblastic and smooth muscle lesions of skin and soft tissue.

The diagnosis of low-grade and pseudosarcomatous spindle cell lesions of skin and soft tissue can sometimes be problematic; in particular, distinction between fibroblastic, myofibroblastic, and smooth muscle proliferations can occasionally pose difficulties on routine histologic examination. We have applied a panel of immunohistochemical markers to a series of spindle cell lesions of skin and soft tissue to assess the utility of the differential expression of smooth muscle and myofibroblastic-associated markers. Twenty-eight cases of nodular fasciitis, 42 cases of fibromatosis, and 3 cases of myofibroblastic sarcoma were stained with antibodies against smooth muscle actin (SMA), smooth muscle myosin (SMMS), calponin, and high-molecular weight caldesmon (h-caldesmon). For comparison, 12 cases of cutaneous leiomyoma and 8 cases of leiomyosarcomas involving superficial soft tissues and fascia were studied with the same panel of antibodies. Thirty-eight of 42 cases of fibromatosis were positive for SMA, 42/42 cases were positive for calponin, 39/42 cases were negative for SMMS, and all cases were negative for h-caldesmon. All cases of nodular fasciitis were positive for SMA and calponin, and all were negative for h-caldesmon and SMMS. All cases of myofibroblastic sarcoma were positive for SMA and 2/3 cases for calponin, and were negative for SMMS and h-caldesmon. All cases of cutaneous leiomyoma and leiomyosarcoma were positive for all 4 markers tested. Our results demonstrate a remarkably consistent pattern of reactivity of muscle and myofibroblastic-associated markers in lesions predominantly composed of myofibroblastic spindle cells, characterized by positive staining for SMA and calponin and absence of reactivity for SMMS and h-caldesmon. Application of this panel of stains may be of aid in the differential diagnosis of low-grade myofibroblastic lesions such as nodular fasciitis and fibromatosis from smooth muscle tumors of skin and soft tissue. This panel may additionally be of assistance in the diagnosis of myofibroblastic sarcoma.

Actins↗
PubMed2006

Applications and limitations of immunohistochemistry in the diagnosis of malignant mesothelioma.

Malignant mesothelioma is an uncommon malignant epithelial neoplasm originating from the serosal surface of body cavities. Because serosal surfaces are a common site of metastatic spread for a variety of malignant neoplasms originating from internal organs, separating malignant mesothelioma from metastatic tumors is of clinical importance. The diagnosis of malignant mesothelioma is complex and usually requires a multimodal approach that includes careful clinical history and physical examination, imaging studies, and tissue sampling for multimodal evaluation including routine histology, histochemistry, electron microscopy, and immunohistochemical tests. Of these, immunohistochemistry has emerged as the most valuable and readily available modality for the routine evaluation of these tumors. Unfortunately, no specific antibodies have yet been developed that can be accepted as exclusive for these tumors. The immunohistochemical diagnosis of malignant mesothelioma therefore depends on the use of a panel of stains that includes markers that are commonly expected to react with these tumors ("positive" markers) and markers that are not commonly expected to react with these tumors ("negative" markers). Additionally, the selection and utility of these various markers can vary considerably based on a constellation of circumstances, including patient sex, histologic appearance of the tumor (ie, epithelioid vs. sarcomatoid, etc), and various other clinical circumstances. Herein, we will review the currently available immunohistochemical markers used for the diagnosis of malignant mesothelioma and offer suggestions for the use of appropriate panels of stains based on specific morphologic types and clinical circumstances.

Biomarkers, Tumor↗
PubMed2006

Sclerosing paraganglioma: report of 19 cases of an unusual variant of neuroendocrine tumor that may be mistaken for an aggressive malignant neoplasm.

Nineteen cases of a distinctive variant of paraganglioma characterized by extensive collagen deposition resulting in a pattern of growth that resembled an invasive malignant neoplasm are described. The patients were 3 men and 16 women, 32 to 69 years of age (mean, 50.5 years). The tumors were located in the carotid body region, parapharyngeal region, and mediastinum. Tumor size ranged from 2 to 6 cm in greatest diameter. Grossly, the tumors were described as rubbery to firm, tan-red, and with extensive areas of sclerosis. Histologic examination showed nests and cords of tumor cells separated by broad bands of fibrous tissue. The tumor cells ranged from round to polygonal with abundant cytoplasm to elongated spindle cells with scant cytoplasm. Nuclear cytomegaly was present focally enhancing the atypical appearance of the tumor cell population in 17 cases. Mitoses were sparse (<1 x 10 HPF), and there was no evidence of necrosis in any of the cases. Foci of vascular and perineural invasion were present in 2 and 4 cases, respectively. The most striking morphologic feature was the presence of irregular cords and bands of hyalinized fibrous tissue that compartmentalized the lesion into irregular nests, islands, or cords of tumor cells, imparting them with an infiltrative appearance. All the tumors showed positive immunostaining for chromogranin, synaptophysin, and monoclonal neuron specific enolase. S-100 protein stains identified a sustentacular cell network, whereas cytokeratin AE1/AE3 was negative in all cases. Clinical follow-up in 14 cases, ranging from 2 months to 20 years (mean follow-up, 6.6 years) showed evidence of local recurrence in 2 cases and the development of a separate tumor in the contralateral neck in 1 case. The remainder of patients were free of recurrence or metastasis following simple local excision. Because of the prominent sclerosis, a diagnosis of an invasive malignant neoplasm was initially considered in the majority of cases. Sclerosing paraganglioma should be included in the differential diagnosis of sclerosing lesions of the head and neck region and mediastinum. Appropriate immunohistochemical stains may be of aid for establishing the correct diagnosis.

Adult↗
PubMed2006

Lipoblastic nerve sheath tumors: report of a distinctive variant of neural soft tissue neoplasm with adipocytic differentiation.

Benign nerve sheath tumors of soft tissue can occasionally adopt unusual or unfamiliar morphologic appearances that may introduce difficulties for diagnosis, such as multinucleation, bizarre nuclei, intranuclear vacuoles, and other degenerative changes. Tumor cells adopting a signet-ring or lipoblast-like configuration, however, are mostly associated with epithelial malignancies, liposarcoma and melanoma, and have been only rarely observed in spindle cell tumors of soft tissue. We report 5 cases of benign nerve sheath neoplasms that displayed prominent signet-ring cells with lipoblast-like features. The cases presented as solitary soft tissue masses in the groin, thigh, retroperitoneum, and shoulder in 4 men and 1 woman between the ages of 31 to 57 years. Four tumors predominantly showed features of schwannoma and one of neurofibroma; however, intimately admixed with the spindle cell population, there were also numerous scattered mature adipocytes as well as lipoblast-like cells displaying a signet-ring cell appearance. Immunohistochemical studies showed strong S-100 protein positivity in the spindle cells as well as in the signet-ring lipoblast-like cells and the mature adipocytes. The signet-ring cells were negative for mucin stains, cytokeratin, EMA, CEA, and several other differentiation markers. Ultrastructural examination was performed in 2 cases. The signet-ring cells contained large cytoplasmic lipid droplets that displaced the nuclei to the periphery, consistent with lipoblastic differentiation, whereas complex, interdigitating cytoplasmic processes covered by basal lamina material characteristic of nerve sheath differentiation could be identified in the spindle cells. Four patients for whom follow-up was available were alive and well with no evidence of recurrence over a period of 28 to 116 months (median follow-up, 50 months). The presence of mature fat and signet-ring lipoblast-like cells within a nerve sheath neoplasm is quite rare and may signify a process of aberrant differentiation. Neurogenic tumors should be added in the differential diagnosis of spindle cell tumors capable of displaying prominent signet-ring cell features.

Adenocarcinoma↗
PubMed2006

Cystic well-differentiated neuroendocrine carcinoma (carcinoid tumor): a clinicopathologic and immunohistochemical study of two cases.

Two cases of primary neuroendocrine carcinoma (carcinoid tumor) arising in the walls of a multilocular thymic cyst (MTC) are described. The patients were 2 men, ages 36 and 44 years. Clinically, the patients had chest pain, cough, and dyspnea. Radiographic evaluation demonstrated the presence of anterior mediastinal tumor in both patients, and complete surgical resection of the tumor mass was performed. The tumors measured approximately 6 and 8 cm in greatest dimension and were cystic with solid areas but did not show areas of necrosis or hemorrhage. Histologic examination revealed a cystic tumor with features similar to those previously described for MTCs. In addition, in the walls of the cystic structures, there was cellular proliferation arranged in a nesting growth pattern, similar to the more solid areas of the tumor. The tumor was characterized by a homogenous cellular proliferation with mild cellular atypia and no more than 2 mitotic figures per 10 high-power fields. Immunohistochemically, the tumor cells showed strong positive reactions for keratin and neuroendocrine markers, ie, chromogranin and synaptophysin. Both patients were alive after periods of 12 and 18 months.

Adult↗
PubMed2006

Thymoma classification: current status and future trends.

The classification of thymic epithelial neoplasms has been a controversial topic for many years. Recent advances in diagnostic methods and renewed interest in the biology of these tumors has led to efforts by investigators to shed new light on their biologic behavior and to offer novel perspectives on these unusual neoplasms. Several new classification schemes have been proposed, including the new World Health Organization schema for the histologic typing of tumors of the thymus. We review the current status of thymoma classification and comment on problem areas and future trends that may offer a more pragmatic approach to these tumors.

Adolescent↗
PubMed2006

Micropapillary urothelial carcinoma of the upper urinary tract: Clinicopathologic study of five cases.

We report 5 cases of micropapillary urothelial carcinoma (MPUC) involving the renal pelvis (2), renal pelvis and ureter (2), and proximal ureter (1). The patients were 2 women and 3 men, ages 65 to 92 years (mean, 76.0 years). All tumors showed a high-grade transitional cell carcinoma component, and in 3 cases, there also were areas of in situ carcinoma. The case involving only the ureter occurred in a 65-year-old man with a history of nephrectomy 12 years previously for urothelial carcinoma of the renal pelvis. The tumor recurred in the ureteral stump. In all cases, areas displaying micropapillary architecture were observed. In 2 cases the micropapillary areas were noninvasive; in 1 case a pure invasive pattern was seen; and in 2 cases a mixed invasive and noninvasive pattern was present. the micropapillary pattern was invasive; and the case involving the ureteral stump contained invasive and noninvasive micropapillary carcinoma. All patients died of their tumors from 3 to 24 months after initial diagnosis. MPUC involving the renal pelvis and ureter is associated closely with advanced stages of disease and has highly aggressive behavior. Recognition of this growth pattern is important for prognosis and avoiding misdiagnosis with papillary renal cell carcinoma and other tumors.

Aged↗
PubMed2006

Thyroid tumors with a follicular growth pattern: problems in differential diagnosis.

Tumors of the thyroid characterized by a follicular growth pattern constitute the most common type of lesion of this organ encountered by pathologists. The vast majority of such lesions do not pose difficulties for histopathologic interpretation. A subset of these tumors, however, can represent a serious challenge for diagnosis. Thyroid tumors with a follicular growth pattern include a broad range of lesions that range from benign, hyperplastic nodules to follicular adenomas to follicular carcinomas. In addition, other types of tumors belonging in separate diagnostic categories can also present histologically with a follicular growth pattern, including the follicular variant of papillary thyroid carcinoma and medullary carcinoma. The histologic features and diagnostic criteria used for distinguishing among these conditions can often be subtle and subjective.

Adenocarcinoma, Follicular↗
PubMed2006

Pulmonary artery sarcoma: a clinicopathologic and immunohistochemical study of 12 cases.

We report 12 cases of pulmonary artery sarcoma. The mean age at diagnosis was 48.4 years. Based on histomorphologic features and immunohistochemical findings, 2 tumors were classified as rhabdomyosarcoma, 4 as leiomyosarcoma, 1 as osteogenic sarcoma, 1 as angiosarcoma, and 4 as high-grade sarcoma. All patients underwent surgery. In addition, 7 patients received neoadjuvant or adjuvant therapy. Five patients died 3 to 23 months after surgery. Three patients were still alive at 8, 27, and 68 months at last follow-up. Another 3 patients were alive at 2, 15, and 40 months and then lost to follow-up. The 2 patients with the longest survival (40 months and 68 months) had a diagnosis of leiomyosarcoma. Both patients with rhabdomyosarcoma died at 3 months after surgery. Pulmonary artery sarcoma is an uncommon entity with a poor prognosis. The role of early diagnosis, histologic classification, surgical treatment, and adjuvant therapy in patient outcome is discussed.

Adult↗
PubMed2005

The role of microRNA genes in papillary thyroid carcinoma.

Apart from alterations in the RET/PTC-RAS-BRAF pathway, comparatively little is known about the genetics of papillary thyroid carcinoma (PTC). We show that numerous microRNAs (miRNAs) are transcriptionally up-regulated in PTC tumors compared with unaffected thyroid tissue. A set of five miRNAs, including the three most up-regulated ones (miR-221, -222, and -146), distinguished unequivocally between PTC and normal thyroid. Additionally, miR-221 was up-regulated in unaffected thyroid tissue in several PTC patients, presumably an early event in carcinogenesis. Tumors in which the up-regulation (11- to 19-fold) of miR-221, -222, and -146 was strongest showed dramatic loss of KIT transcript and Kit protein. In 5 of 10 such cases, this down expression was associated with germline single-nucleotide changes in the two recognition sequences in KIT for these miRNAs. We conclude that up-regulation of several miRs and regulation of KIT are involved in PTC pathogenesis, and that sequence changes in genes targeted by miRNAs can contribute to their regulation.

Base Sequence↗
PubMed2005

Papillary endobronchial squamous cell carcinoma.

A case of papillary endobronchial squamous cell carcinoma incidentally discovered on routine imaging studies is described. The patient, a 75-year-old woman, underwent imaging studies as part of a standard evaluation for a fracture on the right side of the hip. Chest radiographs were unremarkable other than for a nodular opacity overlying the left hemidiaphragm. Computed tomography of the chest, however, demonstrated an elongated, irregular mass in the right lower lobe that appeared to be associated with an adjacent segmental right lower lobe bronchus. Endoscopy followed by surgical resection was undertaken, revealing a tan, soft mass measuring 1.5 x 1.3 x 0.8 cm that was confined to the bronchus and did not appear to extend into the surrounding lung parenchyma. Microscopically, the mass showed a papillary, superficial squamous cell carcinoma confined to the bronchial mucosa without invasion of adjacent structures. The pathological and imaging features of this unusual variant of bronchogenic carcinoma are reviewed as well as the radiological differential diagnosis of endobronchial lesions. To our knowledge, this is the first report that describes the computed tomographic features of this rare lesion.

Aged↗
PubMed2005

Problem areas and inconsistencies in the WHO classification of thymoma.

The morphologic classification of thymoma has undergone numerous revisions in recent years and has been under continuous debate for the past several decades. With the introduction of the World Health Organization (WHO) schema for the classification of thymic epithelial neoplasms in 1999, a major step was taken toward achieving uniformity in the nomenclature of these tumors. A more recent iteration of the WHO morphologic classification of thymic epithelial neoplasms has now been published. Although these efforts have certainly contributed to clarifying many issues related to the pathology of thymoma, several problem areas and inconsistencies still remain surrounding this proposed schema. The purpose of this review is to address these problem areas, in particular as it relates to terminology, histopathologic criteria for diagnosis, and the prognostic significance for the various categories of the WHO schema.

Humans↗
PubMed2005

Thymic carcinoma: update of current diagnostic criteria and histologic types.

Thymic carcinomas are rare tumors thought to derive from thymic epithelium. Because of the complex embryological origin of the thymus, whose development includes contributions from the third and, to a lesser extent, the fourth pharyngeal pouches, thymic carcinomas are endowed with great morphologic heterogeneity. A large number of histologic types have been described that resemble tumors arising in other organs. Unfortunately, no definitive pathognomonic histological features or immunohistochemical markers are associated with these tumors, making them a real challenge for diagnosis. Because of their close similarity with tumors arising at other organs, the diagnosis of thymic carcinoma must be regarded, for the most part, as a diagnosis of exclusion. This review will focus on current criteria for diagnosis of these tumors, with a review of the various histopathologic appearances that they can adopt.

Biomarkers↗