Showing papers by "Saul Suster published in 2006"

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

Abstract: 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.

Thymoma classification: current status and future trends.

Abstract: 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.

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.

Abstract: 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.

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

Abstract: 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.

Vulvar Toker Cells: The Long-awaited Missing Link: A Proposal for an Origin-based Histogenetic Classification of Extramammary Paget Disease

Abstract: To the Editor: The histogenesis of extramammary Paget disease (EMPD) has long been a subject of debate and controversy. Nowadays, it is generally agreed that at least two forms of the disease can be delineated, namely primary and secondary, with the latter representing secondary involvement from an underlying carcinoma originating most commonly in the lower gastrointestinal or urinary tract. As for the primary disease, skin adnexa (eccrine or apocrine glands), ectopic mammary glands, or pluripotential germinative cells in the epidermis and other structures have been implicated as a possible source of neoplastic cells. The recent description of vulvar Toker cells in the Journal by Drs. Willman, Golitz, and Fitzpatrick offers an attractive analogy with the breast, where a similar condition is referred to as mammary Paget disease (MPD). In this location, over 95% of cases of MPD are associated with an underlying ductal carcinoma, and the rest is thought to arise from Toker cells described in 1970. The same seems to be true for rare cases of Paget disease involving ectopic breast adjacent to a supernumerary nipple. We wonder why the same approach could not be applied for the anogenital area and the vulva in particular. This anatomic site contains structures that were originally variously called ectopic breast tissue, supernumerary breast tissue, and most recently, interpreted as anogenital mammary-like glands (MLG). These have been shown to be a normal constituent of this area, and lesions involving these structures have been demonstrated to manifest a striking homology with those seen in the breast. In this regard, the following question arises: why should EMPD differ from MPD histogenetically, if all anatomic conditions are so similar? Below are some lines to support the analogy. It is known that primary EMPD (without underlying carcinoma of internal organs) affects most often vulvar and perianal areas, where anogenital MLG are found in highest concentrations. There have been several documented cases of EMPD with an underlying ductal carcinoma involving anogenital MLG, and this is also in accordance with our experience (Fig. 1). EMPD has a notorious propensity for recurrences, and this can be partly explained by the presence of neoplastic cells residing in anogenital

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

Abstract: 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.

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

Abstract: 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.

Diagnosis of thymoma

Abstract: The diagnosis of thymic epithelial neoplasm has been a topic of controversy for many years. Reasons for this include the lack of predictive value associated with the morphology of these tumours and the multiplicity of classification schemes and terminologies proposed over the years. Recently, a new classification schema was introduced by the World Health Organization (WHO) in an attempt to standardise nomenclature and facilitate the diagnosis of primary thymic epithelial neoplasms. This schema, although not originally intended as a new histological classification, but rather as a means for translating equivalent terms from the various existing classifications, has represented a major step forward in this direction. However, problems still exist with the WHO schema, particularly with some of the criteria for the various histological subtypes as well as with issues of interobserver reproducibility. For this reason, we favour using a much more simplified approach to the morphological classification of thymic epithelial neoplasms. A personal approach to the morphological diagnosis of thymoma is described, with a brief explanation for the rationale for simplifying the existing diagnostic categories.

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

Abstract: 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.

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

Abstract: 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. 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. Micropapillary urothelial carcinoma (MPUC) is a recently described, rare variant of high-grade urothelial carcinoma. 1 In the bladder, the incidence reported in different series for this unusual variant of urothelial carcinoma is between 0.7% and 6%. 2,3 Cases involving the ureter are rare and have been presented as single case reports or as a part of secondary involvement in larger bladder cancer series. 2-4 To the best of our knowledge (with the exception of 1 case mentioned in a letter to the editor 5 ), cases of MPUC involving the renal pelvis have not been described in detail. We describe the clinicopathologic findings in 5 cases of MPUC of the renal pelvis and ureter. The clinical significance and histologic differential diagnosis of these lesions is discussed.

Micropapillary Urothelial Carcinoma of the Upper Urinary Tract

Abstract: 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. 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.

Expression of CD30 (Ber-H2) in nasopharyngeal carcinoma, undifferentiated type and lymphoepithelioma-like carcinoma. A comparison study with anaplastic large cell lymphoma

Abstract: Aims : Undifferentiated nasopharyngeal non-keratinizing carcinoma (UNPC), formerly known as lymphoepithelioma, frequently metastasizes at an early stage to regional lymph nodes and, thus, may be difficult to distinguish from Hodgkin's lymphoma (HL) or anaplastic large cell lymphoma (ALCL). CD30 expression is a useful diagnostic stain in both HL and ALCL, but its expression in UNPC deserves clarification. The aim of this study was to evaluate CD30 expression in UNPC and lymphoepithelioma-like carcinoma (LELC) from other anatomic locations and compare it with ALCL and squamous cell carcinoma (SCC). Methods and results : CD30 immunoreactivity was examined in 38 cases of primary or metastatic UNPC, six cases of LELC, 10 cases of SCC and seven cases of ALCL. CD30 immunoreactivity was observed in four of 38 (10.5%) cases of UNPC. CD30 staining was absent in all cases of LELC (0/6) and SCC (0/10). All cases of ALCL (7/7) were strongly positive for CD30. Conclusions : The majority of cases of UNPC are immunohistochemically negative for CD30; however, a small subset of cases expresses CD30 antigen. These findings provide additional evidence that CD30 expression is not restricted to neoplasms of lymphoid origin. This should be taken into consideration when interpreting CD30 immunohistology and the possibility of UNPC.

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

Abstract: 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 homogeneous 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.

Pathology of the thymus and mediastinum

Abstract: This issue of Pathology Case Reviews is devoted to the topic of pathology of the thymus and mediastinum. Many advances have been made in recent years in our understanding of tumor processes that may involve this anatomic region. The development of newer monoclonal antibodies, as well as the advent of molecular techniques, has expanded our understanding of neoplastic processes and allowed us to gain insights into some of the diseases that can affect the mediastinum. In the present issue, a variety of different areas and disease processes affecting the thymus and mediastinum is covered, ranging from primary thymic epithelial tumors, neuroendocrine neoplasms, benign conditions that may simulate malignant tumors clinically, ectopic tissues that may give rise to tumors in the anterior mediastinum, unusual soft tissue neoplasms involving the mediastinal compartment, and malignant teratomatous lesions to neuroendocrine neoplasms. Neuroendocrine carcinomas of the thymus have represented for many years a controversial topic. Although rare, these tumors are responsible for significant morbidity

Spectrum of pathologic features in neuroendocrine neoplasms of the mediastinum

Abstract: Neuroendocrine tumors arising in the mediastinum are rare. They all share in common the consistent expression of certain morphologic, immunohistochemical, and ultrastructural features indicative of their neuroendocrine lineage. Although some of them may share very similar morphologic characteristics, differences in biologic behavior among some of these tumors mandate careful assessment and specific diagnosis. A number of unusual morphologic variants of neuroendocrine neoplasms have been described in recent years in the mediastinum. The present review highlights some important pitfalls in their interpretation and offers some insights for their separation into specific entities. In addition, issues and controversies regarding the current classification of primary neuroendocrine carcinomas of the thymus are also discussed.