Sclerosing poorly differentiated liposarcoma: clinicopathological, immunohistochemical and molecular analysis of a distinct morphological subtype of lipomatous tumour of soft tissue.

AIMS: To present eight cases of a distinctive morphological subtype of lipomatous tumour of soft tissue. METHODS AND RESULTS: The clinicopathological, immunohistochemical and molecular pathological features of these tumours were analysed. The tumours were characterized by dense stromal sclerosis containing singly scattered pleomorphic atypical cells with lipoblastic features. The tumours occurred in four women and four men, aged 39-90 years (mean = 63). They were located in the retroperitoneum, thigh, retropubic space, arm and spermatic cord. Four cases arose de novo and four cases presented as local recurrences of previously resected liposarcomas. MDM2 amplification and cyclophosphamide doxorubicin hydrochloride (adriamycin), vincristine and prednisolone (CHOP) translocation was studied in seven cases by fluorescence in situ hybridization. High-level amplification of MDM2 at 12q13-15 was observed in 4/7 cases. All cases were negative for the CHOP translocation; in one MDM2+ case, the CHOP gene showed amplification but no translocation. Three patients died from their tumours from 1 to 6 years after their last surgery with lung metastases. CONCLUSIONS: The tumours described appear to represent an unusual morphological variant of poorly differentiated liposarcoma associated with aggressive behaviour, and may represent a common end-stage pathway for various types of liposarcoma.

Primary peritoneal mesotheliomas in children: a clinicopathological and immunohistochemical study of eight cases.

AIMS: To present eight cases of primary diffuse peritoneal malignant mesothelioma in children <15 years old, with a discussion of the pitfalls of this diagnosis in the paediatric age group. METHODS AND RESULTS: The cases were selected based on the following criteria: (i) primary peritoneal neoplasms confined grossly or radiographically to the abdominal cavity; (ii) negative history of previous or another associated malignancy; (iii) histopathological confirmation. All patients (five female, three male) presented clinically with symptoms of abdominal pain, distention and ascites. Grossly, the tumours showed multiple, diffuse peritoneal nodules. Histologically, seven cases corresponded to epithelioid mesotheliomas and one case displayed biphasic (epithelioid and spindle) cellular proliferation. Immunohistochemical studies for cytokeratin (CK) 5/6, calretinin and low-molecular-weight CK (CAM5.2) showed strong cytoplasmic positivity in the neoplastic cells. Three patients were treated by chemotherapy. On clinical follow-up, four patients with epithelioid mesotheliomas were alive and well from 12 to 18 months after initial diagnosis; one patient with a mixed (biphasic epithelioid/sarcomatoid) mesothelioma died of tumour 24 months after diagnosis. CONCLUSIONS: Peritoneal malignant mesothelioma in children is a rare condition that can introduce difficulties in histopathological diagnosis.

Diagnosis of thymoma.

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.

The down-regulated in adenoma (DRA) gene encodes an intestine-specific membrane glycoprotein.

The protein product of the DRA gene, a gene whose expression is down-regulated in colon adenomas and adenocarcinomas, is a membrane glycoprotein and a member of a family of sulfate transporters. It is expressed in the intestinal tract (duodenum, ileum, cecum, distal colon), but not in the esophagus or stomach. DRA mRNA expression is restricted to the mucosal epithelium, and DRA protein expression is further limited to the columnar epithelial cells, particularly to the brush border. Consistent with its expression in the differentiated columnar epithelium of the adult human colon, DRA is first expressed in the midgut of developing mouse embryos at day 16.5, corresponding with the time of differentiation of the epithelium of the small intestine. A model for the structure of the DRA protein is proposed and its possible role in colon tumorigenesis is discussed.

Chromophobe renal cell carcinoma with microcystic and adenomatous arrangement and pigmentation--a diagnostic pitfall. Morphological, immunohistochemical, ultrastructural and molecular genetic report of 20 cases.

We present clinical, morphological, immunohistochemical, ultrastructural and molecular genetic features of 20 cases of a peculiar form of chromophobe renal cell carcinoma (CRCC) with morphology differing from that of conventional CRCC. Microscopically, the typical features of the tumors were microcystic arrangement and formation of adenomatous structures. Microcystic areas were composed of smaller eosinophilic and bigger pale cells having cytological appearance typical of conventional CRCC. Cytological features of the adenomatous structures were mostly different from those of conventional CRCC. They had a typical columnar arrangement with nuclei positioned at the base of the glandular structures and a small amount of a deeply eosinophilic cytoplasm often endowed with brush border facing the lumen of the glands. In addition, all the tumors showed a brown pigmentation. The pigmentation was located mostly extracellularly, where it formed pools of heavy deposits. Microscopic calcifications present in all cases formed psammoma bodies or else the calcifications were more extensive and amorphous in shape. Ultrastructurally, the cells showed features characteristic of CRCC: typical cytoplasmic vesicles were 100-700 nm in size and mitochondria had tubulovesicular, lamellar or circular cristae. Some tumor cells contained dark, variously sized electron-dense pigment granules. Neither melanosomes nor membrane-bound neurosecretory granules were seen. Using fluorescence in-situ hybridization probes for chromosomes 1, 2, 6, 10, 13, 17 and 21, the tumors revealed massive loss of tested chromosomes typical for conventional CRCC. Monosomy of chromosomes 1, 2, 6, 10, 13 and 21 was found in 100, 36, 91, 82, 82, 82 and 64% of cases, respectively. None of the cases showed mutation of exons 9, 11, 13 and 17 of the c-kit gene. The important feature of pigmented microcystic chromophobe renal cell carcinoma is a relatively benign biological behavior and the absence of distant metastases and sarcomatoid transformation.

Epithelioid leiomyosarcoma of the skin and subcutaneous tissue. Clinicopathologic, immunohistochemical, and ultrastructural study of five cases.

This report describes five cases of an unusual variant of malignant smooth-muscle neoplasm involving the skin and subcutaneous tissue characterized by a proliferation of predominantly round to oval epithelioid cells with abundant eosinophilic cytoplasm. Of the five patients, four were men, one a woman; ages ranged from 69 to 85 years (mean, 76.4). The size of the lesions varied from 1.2 to 2.5 cm; two were located in the scalp, two in the face, and one in the back of the neck. Immunohistochemical evaluation of the tumor cells showed immunoreactivity for actin and vimentin in all cases and negative labeling for desmin, S-100 protein, keratin, epithelial membrane antigen, HMB-45, factor VIII, and alpha-1-antichymotrypsin. Ultrastructural examination showed features of smooth muscle differentiation, that is, focal plasmalemmal densities, basement membrane material, and cytoplasmic filaments with focal condensations. All patients were treated by surgical excision and two also with post-operative radiotherapy. Two cases recurred after 1 year, requiring wide excision. A second recurrence from one of these cases showed the emergence of a highly anaplastic, pleomorphic spindle cell sarcoma; the patient died of unrelated causes, with evidence of persistent disease, after 2 years. In the remainder of cases, the patients were alive and well with no evidence of recurrence or metastasis from 2 to 6 years. Because of the unusual morphologic features of this variant of smooth-muscle tumor it may be confused with a variety of primary and metastatic neoplasms of the skin, including malignant melanoma, epithelioid sarcoma, and metastatic carcinoma. Epithelioid leiomyosarcoma should be recognized as a distinct morphologic variant of primary cutaneous smooth muscle neoplasm and should be considered in the differential diagnosis of epithelioid neoplasms in dermal and superficial soft tissue locations.

Epithelioid and spindle-cell hemangioendothelioma of the spleen. Report of a distinctive splenic vascular neoplasm of childhood.

A case of a distinctive vascular neoplasm of the spleen in a 3-year-old boy is described. The tumor was characterized histologically by a biphasic growth pattern, with discrete nodular areas composed of atypical round, epithelioid cells with large nuclei and prominent nucleoli, and areas showing an intricate proliferation of vascular channels lined by elongated spindle cells. Immunohistochemical studies showed cytoplasmic staining of the tumor cells with factor VIII-related antigen, Ulex europaeus lectin, and vimentin antibodies. Stains for keratin, actin, desmin, lysozyme, and S-100 protein were negative in the tumor cells. Electron microscopy revealed a fairly cohesive population of cells that contained mature and immature cell junctions, basal lamina material, and surface pinocytotic activity consistent with vascular endothelial cells. Five-year follow-up has shown the patient to be alive and free of disease. This case appears to represent a previously unreported primary vascular neoplasm of the spleen showing combined features of epithelioid and spindle-cell hemangioendothelioma. The lesion should be distinguished from other benign and malignant vascular proliferations of the spleen such as Kaposi's sarcoma, angiosarcoma, and the recently described littoral-cell angioma.

Intranodal hemorrhagic spindle-cell tumor with "amianthoid" fibers. Report of six cases of a distinctive mesenchymal neoplasm of the inguinal region that simulates Kaposi's sarcoma.

We describe six cases of a distinctive spindle-cell neoplasm apparently arising from inguinal lymph nodes in adult patients. The lesions were characterized histologically by highly vascularized, interlacing fascicles of spindle cells circumscribed by an irregular band of sclerosis and hemorrhage, and surrounded by a compressed rim of lymph node remnant. A striking feature observed in all cases was the presence of stellate-shaped areas containing thick collagen fibers (so-called amianthoid fibers). Immunohistochemically, the tumor cells were positive for actin, muscle myosin, and vimentin. Electron-microscopic examination demonstrated features indicative of myofibroblastic and smooth-muscle differentiation. Follow-up has shown no evidence of recurrence or metastases. The lesions appear to represent an intranodal neoplastic proliferation of mesenchymal cells exhibiting benign biologic behavior. The inguinal location, presence of amianthoid fibers, and the striking rim of hemorrhage surrounding the spindle-cell proliferation set this tumor apart from other lesions. It is important to distinguish this entity from nodal involvement by Kaposi's sarcoma, a lesion it may closely resemble.

Immunoreactivity for the human hematopoietic progenitor cell antigen (CD34) in lipomatous tumors.

The human hematopoietic progenitor cell antigen (CD34) recently was shown to react with a variety of nonhematopoietic tissues and their tumors, including vascular endothelium, dendritic interstitial fibroblastic cells, and endoneurial cells as well as with the neoplastic cells in a variety of mesenchymal neoplasms of unknown etiology, such as Kaposi's sarcoma, dermatofibrosarcoma protuberans, epithelioid sarcoma, gastrointestinal stromal tumors, and solitary fibrous tumors. Additionally, it has been claimed that normal adipocytes may also react with this antibody. We studied a series of 90 lipomatous lesions to examine the pattern of immunoreactivity of the CD34 antigen in adipose tissue neoplasms. The study included 14 lipomas, 19 angiolipomas, 4 atypical lipomas, 18 spindle cell lipomas, 3 renal angiomyolipomas, 1 intramuscular lipoma, and 31 liposarcomas. Immunostains identified a network of CD34+ spindle cells admixed with the adipose tissue elements in all cases of lipoma, angiolipoma, angiomyolipoma, intramuscular lipoma, and well-differentiated lipoma-like liposarcoma. Additionally, the spindle cell component in all cases of spindle cell lipoma were strongly positive for this antigen. Atypical, stellate spindle cells and multinucleated "floret" cells in all cases of atypical lipoma as well as in six of 12 cases of well-differentiated lipoma-like liposarcoma of deep soft tissue were also positive for CD34. Scattered spindle cells in all cases of myxoid liposarcoma and in one case of round cell liposarcoma, as well as the sarcomatous component in one case of "dedifferentiated" liposarcoma, were strongly positive for this antigen. The round cells in myxoid liposarcoma and round cell liposarcoma, the signet-ring and multivacuolated lipoblasts in well-differentiated liposarcoma, and the pleomorphic atypical cells in pleomorphic liposarcoma were uniformly negative. The results of this study appear to indicate that lipomatous tumors may harbor a population of CD34+ interstitial dendritic spindle cells. Overgrowth or clonal expansion of this dendritic cell subpopulation may account for the development of spindle cell lipomas and for the spindle cell component in some cases of "dedifferentiated" liposarcoma.

Epithelioid leiomyosarcoma of the stomach. A case study of the intermediate filaments.

The intermediate filament typing of skeletal and smooth muscle tumors has shown that these neoplasms are characterized by the combined expression of desmin and vimentin intermediate filaments. A case of epithelioid leiomyosarcoma of the stomach was studied by conventional light microscopy and by indirect immunofluorescence using tissue-specific antibodies against intermediate filaments. The tumor cells labeled strongly with vimentin antibodies and were negative for desmin and prekeratin. This peculiar staining pattern may be the result of poor differentiation of the tumor cells with resultant loss of expression of desmin, or may be due to origin from a distinctive smooth muscle cell characterized by the exclusive expression of vimentin intermediate filaments.

Multilocular thymic cyst: an acquired reactive process. Study of 18 cases.

The clinical and pathologic features in 18 cases of multilocular thymic cyst (MTC) of the anterior mediastinum unassociated with Hodgkin's disease or seminoma were studied. The majority of cases were asymptomatic and discovered incidentally on routine chest x-ray. Several patients presented with acute symptoms of chest pain or discomfort, sometimes associated with dyspnea. Two cases had an incidental thymoma, and two had an incidental thymic carcinoma. The main histologic features of MTC included the following: multiple cystic cavities partially lined by squamous, columnar, or cuboidal epithelium (some having features of Hassall's corpuscles); scattered nests and islands of non-neoplastic thymic tissue within the cyst walls, often continuous with the cyst lining; severe acute and chronic inflammation accompanied by fibrovascular proliferation, necrosis, hemorrhage, and cholesterol granuloma formation; and reactive lymphoid hyperplasia with prominent germinal centers. These features suggest that MTC most likely results from the cystic transformation of medullary duct epithelium-derived structures (including Hassall's corpuscles) induced by an acquired inflammatory process. The changes are similar to those sometimes seen in association with thymic Hodgkin's disease and thymic seminoma, which are also probably due to the inflammation that accompanies these tumors rather than to the tumors themselves. We believe that MTC is pathogenetically analogous to a variety of cystic conditions of the head and neck region, for which the common denominator seems to be the induction of cystic transformation in ductular epithelial formations of branchial pouch or related derivation by an acquired inflammatory process.

Mucinous meningioma. Report of an unusual variant of meningioma that may mimic metastatic mucin-producing carcinoma.

An unusual variant of meningioma is described that was characterized by small clusters and strands of meningothelial cells surrounded by abundant mucinous stroma. The unusual appearance of the lesion prompted an initial diagnosis of metastatic mucin-secreting carcinoma (so-called colloid carcinoma) resulting in extensive clinical evaluation in search for a primary. Histochemical studies showed the mucinous material to be composed of strongly sulfated acid mucopolysaccharides rich in hyaluronic acid. Immunohistochemical studies showed strong membrane staining of the tumor cells with epithelial membrane antigen and positive cytoplasmic staining with vimentin antibodies. Ultrastructural examination revealed the characteristic features of meningothelial cells (i.e., abundant long, interdigitating cytoplasmic processes joined by well-developed cell junctions) but failed to demonstrate secretory activity within the neoplastic cells. The prominent mucinous stroma in this case most probably represents a nonspecific reaction of stromal cells to an undetermined stimulus. Mucinous meningioma should be added to the list of morphologic variants of meningioma and should be considered in the differential diagnosis of mucinous lesions in intracranial locations.

Hamartoma of the scalp with ectopic meningothelial elements. A distinctive benign soft tissue lesion that may simulate angiosarcoma.

Five cases of a distinctive benign soft tissue lesion of the scalp in patients ranging from 4 months to 40 years of age are described. Clinically, the lesions appeared as solitary, subcutaneous nodules suggestive of a cystic vascular malformation or other benign condition. Histologically, however, the lesions were characterized by a monotonous, pseudoinfiltrative proliferation of cuboidal epithelioid cells arranged in clusters within the dermis and subcutaneous tissue in intimate association with vessels, adipose tissue, and other connective tissue elements. A prominent feature in all cases was the presence of areas simulating freely anastomosing vascular channels lined by round to spindle-shaped, slightly hyperchromatic epithelioid cells reminiscent of angiosarcoma. Immunohistochemically, these cells were negative for factor VIII-related antigen and Ulex europaeus lectin but were strongly positive with vimentin and epithelial membrane antigen antibodies, this latter being in keeping with the immunohistochemical profile of meningothelial cells. The meningothelial nature of these cells was supported by the electron microscopic demonstration in one case of cells with complex, interdigitating cytoplasmic processes that were joined by scattered cell junctions and contained abundant intracytoplasmic intermediate filaments. The intimate admixture of meningothelial elements with haphazardly arranged connective tissue elements sets these lesions apart from cutaneous meningiomas and warrants their designation as hamartomas with an ectopic meningothelial component.

Histology of the normal thymus.

We present a review of the normal histology of the thymus, with special emphasis on the developmental, morphologic, and immunohistochemical aspects pertinent to the interpretation of thymic lesions in surgical pathology. Attention is drawn to normal variations in histology, embryonal vestiges and developmental defects, involutional and hyperplastic changes, tissue reactions to injury, and biopsy artifacts that may constitute a source of diagnostic problems.

Primary thymic epithelial neoplasms in children.

Primary epithelial neoplasms of the anterior mediastinum in children are very rare. We have studied 10 cases of thymic epithelial neoplasms in children aged 16 years or less and correlated their histologic features with the clinical outcome. The patients' ages ranged from one to 16 years (mean: 10.2); with a male:female ratio of 1.5:1. Nine patients had symptoms attributable to their tumors; one was asymptomatic. Four patients presented in clinical stage I, one in stage IIb, and five in stage IVb. Histologically, the tumors comprised a heterogenous group displaying a range of morphologic appearances: one tumor had the classic features of lymphocyte-rich thymoma of the adult; four were of the lymphocyte-rich type with associated unusual stromal features; two were spindle cell thymomas with cytologic and architectural atypia; and three displayed obvious cytologic features of malignancy (i.e., thymic carcinoma); two in the last group showed features of small cell carcinoma, and the other was an undifferentiated/anaplastic carcinoma. The epithelial nature of the tumors was supported in six cases by positive staining of the tumor cells with keratin antibodies and in two cases by electron microscopic demonstration of desmosomes and intracytoplasmic bundles of tonofilaments within the tumor cells. The prognosis for these patients correlated well with the degree of atypicality exhibited by the epithelial components; it was very poor in patients with small cell and undifferentiated/anaplastic carcinoma (8 months average survival), better for those with atypical spindle cell thymomas (multiple recurrences and metastases but no fatalities over a 15- to 72-month period), and best in those with lymphocyte-rich thymomas without cytologic atypia (no recurrences or metastases over an 8-month to 3-year follow-up).

Micronodular thymoma with lymphoid B-cell hyperplasia: clinicopathologic and immunohistochemical study of eighteen cases of a distinctive morphologic variant of thymic epithelial neoplasm.

We describe 18 cases of a distinctive morphologic variant of primary thymic epithelial neoplasm characterized by a micronodular growth pattern associated with florid lymphoid follicular hyperplasia of the stroma. The tumors occurred in seven women and 11 men aged 41 to 76 years (mean, 58 years). All cases were asymptomatic and discovered incidentally on routine chest radiograph or during coronary artery bypass surgery. The tumors measured from 3 to 10 cm in greatest dimension and were well circumscribed and encapsulated. In seven cases, the lesions were grossly described as cystic or partially cystic masses. Histologically, they were characterized by a proliferation of small tumor nodules separated by abundant lymphoid stroma with prominent germinal centers. The nodules were composed of spindle cells containing oval nuclei devoid of atypia or mitotic activity. Immunohistochemical studies showed strong positivity of the spindle tumor cells for CAM 5.2 and broad spectrum keratin antibodies. The surrounding lymphoid cell population was strongly positive for LCA and L26 and showed a polyclonal pattern of staining for kappa and lambda. Stains for UCHL-1, CD1a, CD3, CD5, and CD99 were negative in the stromal lymphoid cell population. The tumor in one of the patients was associated with active pulmonary tuberculosis, and in another with anemia and splenomegaly of unknown etiology. None of the patients had clinical signs or history of myasthenia gravis or other autoimmune disorders. The present cases are interpreted as an unusual morphologic variant of spindle cell thymoma with prominent B-cell lymphoid hyperplasia. The possible significance of this phenomenon is discussed.

Pleomorphic large cell lymphomas of the mediastinum.

Nine cases of primary non-lymphoblastic, non-Hodgkin's large cell lymphomas of the mediastinum characterized by a highly pleomorphic histologic appearance are described. The patients, four women and five men, were aged 30 to 65 years. All patients presented with symptoms referable to their tumors, including cough, chest pain, dyspnea, pleural effusion, and superior vena cava syndrome. Clinical and pathologic staging in all patients showed that the bulk of the tumor was confined to the chest cavity at the time of initial diagnosis, with local infiltration into the neck, lung hilum, and surrounding mediastinal structures. Three different histological growth patterns were observed: one composed of a diffuse proliferation of pleomorphic, highly atypical cells with bizarre nuclear features that closely resembled a high grade sarcoma; another one composed of sheets of large, epithelial-appearing atypical cells suggestive of anaplastic carcinoma; and another pattern characterized by a pleomorphic proliferation of large lymphoid cells admixed with numerous scattered Reed-Sternberg-like cells reminiscent of the lymphocyte-depleted variant of Hodgkin's disease. Immunohistochemical studies on paraffin-embedded tissue sections in all cases showed positive staining of the tumor cells with CD20 and CD45 antibodies and negative staining with a large panel of markers, including broad-spectrum keratin, CAM 5.2, carcinoembryonic antigen, epithelial membrane antigen, vimentin, actin, desmin, HMB 45, S-100 protein, CD3, CD15, CD30, and CD45RO. Because of their location restricted to the anterior mediastinum, frequent lack of recognizable lymph node architecture, and bizarre cytologic features, the present group of lesions posed difficulties for diagnosis, their correct identification was achieved through the application of a panel of immunohistochemical markers. An awareness of these unusual histologic appearances of primary large cell lymphoma in the mediastinum and inclusion of a broad panel of lymphoid markers are therefore recommended for the evaluation of pleomorphic, undifferentiated malignant neoplasms of this anatomic region.

Thymic carcinoid with prominent mucinous stroma. Report of a distinctive morphologic variant of thymic neuroendocrine neoplasm.

Four cases are described of a distinctive morphologic variant of thymic carcinoid that was characterized by abundant stromal mucin admixed with the neuroendocrine elements resulting in a histologic picture reminiscent of metastatic mucin-secreting carcinoma. The patients were three men and a woman, aged 22 to 43 years. The tumors presented with symptoms of chest discomfort, cough, and dyspnea and were described as large anterior mediastinal masses on chest radiographs and computerized scans. Histologically, all cases showed nests and strands of tumor cells embedded in an abundant lightly eosinophilic, mucinous stroma with small cellular clusters as well as scattered single tumor cells seen floating in the mucin. The mucinous matrix was negative for periodic acid Schiff's and mucicarmine stains; alcian blue stains at pH 2.5 showed strong positivity of the mucinous material; this reaction was abolished by treatment with hyaluronidase, indicating the presence of nonepithelial stromal mucosubstances. Immunohistochemical stains showed strong positivity of the tumor cells with CAM 5.2, chromogranin, synaptophysin, and neuron-specific enolase, and negative staining with carcinoembyronic antigen and epithelial membrane antigen. Electron microscopy done in one case showed abundant dense-core cytoplasmic neurosecretory granules; there was no evidence of glandular secretory activity by the tumor cells. The tumors in two patients behaved in a highly aggressive fashion, with invasion of the chest wall, recurrence, and metastases to the lungs, pleura, and axillary, retroperitoneal, and mesenteric lymph nodes. Thymic carcinoid should be considered in the differential diagnosis of mediastinal neoplasms displaying prominent mucinous features. Application of immunostains and electron microscopy will be of value for establishing the correct diagnosis in this setting.

Primary thymic epithelial neoplasms showing combined features of thymoma and thymic carcinoma. A clinicopathologic study of 22 cases.

Thymic epithelial neoplasms are unusual tumors that may span the gamut from clinically benign, well-differentiated lesions (encapsulated thymoma) to overtly malignant, poorly differentiated neoplasms (thymic carcinoma). It has been commonly believed that lesions displaying obvious cytologic features of malignancy (i.e., thymic carcinoma) represent a unique and separate group that is histogenetically distinct from thymoma. We have studied 22 cases of thymic epithelial neoplasms characterized by the admixture of areas displaying conventional features of thymoma with areas showing features of thymic carcinoma. The tumors occurred in six women and 16 men whose ages ranged from 23 to 83 years (median, 53). The lesions presented in eight patients with symptoms of chest discomfort resulting from the involvement of surrounding structures; in 14 patients, they were asymptomatic and discovered incidentally on routine chest radiographs. Histologically, most tumors showed a combination of conventional thymomatous elements with well-differentiated squamous-cell carcinoma (10 cases), followed by thymoma and poorly-differentiated squamous carcinoma (seven cases) and spindle-cell thymoma with poorly-differentiated squamous carcinoma (five cases). Areas of transition between the two different components could be identified in most cases. In five cases, areas showing the features of clear-cell carcinoma could be seen either arising from squamous carcinomatous elements or within the thymomatous component, and in one case transitions between lymphoepithelioma-like carcinoma and anaplastic carcinoma could be observed. Two patients had a history of myasthenia gravis with biopsy-proven thymomas in whom the tumors had been monitored without treatment for 10 and 14 years before the sudden enlargement of the mass. The resected specimens in both patients showed the emergence of a carcinoma arising from a thymoma. The present cases appear to support the existence of a continuum in the spectrum of differentiation between thymoma and thymic carcinoma, suggesting a close histogenetic relationship between these two conditions. Such findings are important not only for our understanding of these tumors but may also play a significant role in the assessment of the biologic behavior and management of these lesions.

Thymoma with prominent cystic and hemorrhagic changes and areas of necrosis and infarction: a clinicopathologic study of 25 cases.

Twenty-five cases of thymoma with prominent cystic and hemorrhagic changes and areas of necrosis and infarction are presented. The patients were 11 women and 14 men between the ages of 18 and 73 years (median 45.5 years). Clinically, nine patients were asymptomatic and their mediastinal tumor was discovered on routine chest radiograph. Sixteen patients presented with symptoms of chest pain and cough. All patients underwent surgical resection of their tumor. Grossly, the tumors were described as well circumscribed and encapsulated, with the exception of two that showed infiltration of pleura and pericardium. The tumors measured from 4 to 13 cm in greatest dimension. On cut surface they showed prominent cystic areas and foci of hemorrhage and necrosis. Histologically, the tumors contained solid areas showing an admixture of round to oval epithelial cells devoid of atypia admixed with small lymphocytes in varying proportions. Cystic changes with areas of necrosis, infarction, and hemorrhage were present in all cases and comprised extensive areas of the tumors. The areas of infarction showed features of ischemic necrosis and were always intimately associated with vaso-occlusive and thrombotic phenomena and with cystic and hyperplastic changes of adjacent thymic epithelium. Clinical follow-up in 14 patients showed that 11 were alive and well from 1 to 18 years after surgery (median follow-up 9 years). Three patients died: one of complications during the immediate postoperative period, one because of colonic adenocarcinoma 9 years after diagnosis of the mediastinal tumor, and one because of pneumonia 6 years later. The two patients with invasive tumors were lost to follow-up. The present study appears to indicate that areas of hemorrhage and necrosis in well encapsulated, noninvasive thymomas do not portend an adverse prognosis.