Sharon W. Weiss

Dedifferentiated liposarcoma: a clinicopathological analysis of 155 cases with a proposal for an expanded definition of dedifferentiation.

We studied 155 cases of dedifferentiated liposarcoma to define its clinicopathologic features and behavior, in particular how the extent and grade of dedifferentiation affected outcome. Tumors occurred in late adult life (median, 61.5 years: range, 21-92 years), most commonly in the retroperitoneum (106 cases), extremities and trunk (32 cases), and scrotum/spermatic cord (13 cases). The majority of dedifferentiated liposarcomas presented as de novo lesions, whereas the remainder developed as a late complication of a preexisting well-differentiated liposarcoma after an average interval of 7.7 years. At the time of presentation, most of the dedifferentiated liposarcomas displayed extensive areas of high-grade dedifferentiation resembling malignant fibrous histiocytoma or high-grade fibrosarcoma, whereas a minority contained only areas of low-grade dedifferentiation resembling fibromatosis or well-differentiated fibrosarcoma. Divergent myosarcomatous or osteosarcomatous differentiation was observed focally in six cases. The behavior of dedifferentiated liposarcomas was that of a high-grade sarcoma with a local recurrence rate of 41%, a metastatic rate of 17%, and disease-related mortality of 28%. The most important prognostic factor was location in that retroperitoneal tumors had significantly worse survival than those in other sites. Tumors were divided into those having less than or those with more than 25% dedifferentiation, and dedifferentiated zones were classified into low grade or high grade. Neither low-grade dedifferentiation nor a low percentage of dedifferentiation was associated with an improved outcome for the tumors examined in this study; however, in no cases was the absolute size of the dedifferentiated focus <2 cm. Therefore, this study did not determine a minimum, or threshold, amount of dedifferentiation below which outcome was more favorable. The behavior of liposarcomas in which the dedifferentiated component was entirely low grade was more similar to that of traditional dedifferentiated liposarcoma than to that of well-dedifferentiated liposarcoma. Our study supports the expansion of the definition of dedifferentiated liposarcoma to include tumors with low-grade dedifferentiation and also suggests that low-grade dedifferentiation represents a precursor lesion of high-grade dedifferentiation.

CD-34 and keratin expression distinguishes solitary fibrous tumor (Fibrous mesothelioma) of pleura from desmoplastic mesothelioma

Solitary fibrous tumors (SFTs) often involve the pleura and also may encompass the peritoneum and nonserosal sites. On occasion SFTs mimics other neoplasms, including desmoplastic mesothelioma. CD-34, initially characterized as a hematopoietic progenitor cell antigen, recently has been identified in a small number of SFTs. Based on this observation, we compared the keratin, vimentin, and CD-34 expression of 19 SFTs and eight desmoplastic mesotheliomas. Fifteen of 19 SFTs (78.9%) expressed CD-34, whereas keratin expression was absent in all SFTs. In contrast, none of the desmoplastic mesotheliomas expressed CD-34 and keratin expression was found in seven of eight (87.5%). Vimentin expression was noted in 18 of 19 SFTs and in seven of eight desmoplastic mesotheliomas. We conclude that CD-34 expression distinguishes SFT from desmoplastic mesothelioma. Additionally, the results of our study support the idea that SFT is not derived from or related to conventional mesothelium.

Stromal tumors of the anorectum: a clinicopathologic study of 22 cases.

Stromal tumors of the anorectum are a rare group of mesenchymal tumors that often have a protracted clinical course. We sought to determine which clinical, morphologic, and immunophenotypic features correlated with an adverse outcome in 22 patients with anorectal stromal tumors. An adverse outcome, defined as either tumor recurrence or metastasis, occurred in nine patients. Seven patients had metastases, two of whom also had local recurrences. Four of these patients also died from their disease. One patient had one local recurrence, and one patient had two local recurrences; neither of these patients had metastases. Recurrences were found as long as 103 months and metastases as late as 117 months after initial presentation. However, for patients without an adverse outcome, maximum follow-up was only 84 months. Thus both recurrence and metastasis may not appear until several years after treatment, indicating that a long-term follow-up period, probably longer than available for many tumors without an adverse outcome in this study, is needed before a patient can be considered to be cured. Tumor size greater than five centimeters correlated with an adverse outcome. However, given the protracted course of these tumors and the relatively limited follow-up available, other features such as location within the muscularis propria, mitotic activity, necrosis, and pleomorphism that did not significantly correlate with an adverse outcome may become significant with longer follow-up periods. We also found that on the basis of morphologic appearance and whether tumors were confined to the submucosa or located within the muscularis propria, anorectal stromal tumors could be divided into three groups, and that the behavior of anorectal stromal tumors may also depend upon their phenotype. The largest group of 17 tumors was located within the muscularis propria, mitotically active, and composed of densely cellular spindle-shaped cells. A second group of two tumors was also located within the muscularis propria and was composed of spindle-shaped cells, but lacked dense cellularity and mitotic activity. The third group was composed of three submucosal, polypoid tumors.

Stromal tumors of the abdominal colon: a clinicopathologic study of 20 cases.

Stromal tumors of the abdominal colon, the least common of all gastrointestinal stromal tumors, have not been well characterized. They have often been lumped with stromal tumors of the anorectum in order to achieve significant numbers for analysis, yet there are no data to prove that stromal tumors from these two sites are the same. In this study, we evaluated 20 colonic stromal tumors to identify clinical, morphologic, and immunophenotypic features that were useful in discriminating between those that had metastasized or caused death from those that had not metastasized or caused death. We found that colonic stromal tumors are morphologically heterogeneous, and the malignant ones are clinically aggressive. They often have metastases at presentation, and cause death in a short time. An infiltrative growth pattern in the muscularis propria, invasion of the mucosa, and high mitotic counts correlated significantly both with metastases and with death from tumor. We also found that dense cellularity correlated significantly with metastases, but not with death, and that coagulative necrosis correlated with death, but not with metastases.

Crystal-storing histiocytosis associated with lymphoplasmacytic lymphoma mimicking weber-christian disease: Immunohistochemical, ultrastructural, and gene-rearrangement studies

A case of crystal-storing histiocytosis associated with lymphoplasmacytic lymphoma is presented. Unlike previous cases, this patient presented with signs and symptoms suggestive of Weber-Christian disease. Biopsy of subcutaneous nodules showed numerous deposits of crystal-storing histiocytes with lymphoplasmacytic cells, the latter exhibiting light chain restriction (lambda-chain) with a predominance of immunoglobulin (Ig)G heavy chain. Polymerase chain reaction (PCR) analysis of CDR-II* region of the immunoglobulin heavy chain locus confirmed monoclonality of the lymphoplasmacytic cells in the nodule. Electron microscopy showed polygonal-shaped amorphous crystals, characteristic of immunoglobulin in the histiocytic cells. Crystal-storing histiocytosis should be examined by immunohistochemical and DNA analysis to confirm or exclude the possibility of lymphoplasmacytic lymphoma.

Ossifying Fibromyxoid Tumor of Soft Parts with Stromal Cyst Formation and Ribosome-Lamella Complexes

Ossifying fibromyxoid tumor of soft parts (OFMT) is a recently named soft tissue tumor of uncertain nature. A case is described that presented in a 13-year-old boy as a discrete mass in the muscles of the lower abdominal wall. Light microscopy showed, in addition to the typical features of this entity, microcysts formed by accumulations of the myxoid stroma. Bone formation was lacking. Tumor cells were strongly immunoreactive for vimentin and glial fibrillary acidic protein and weakly so for S-100 protein. A few cells stained for desmin and alpha-smooth muscle actin. Ultrastructurally, there were abundant, patternless cytoplasmic intermediate filaments; short, poorly interdigitating processes; and discontinuous segments of thick external lamina. In addition, several cells contained typical ribosome-lamella complexes in small groups. Ribosome-lamella complexes occur in neoplastic hematopoietic cells but are uncommon in solid tumors, particularly those affecting the soft tissues. These findings extend the range of appearances described for OFMT, which is added to the list of tumors in which ribosome-lamella complexes have been demonstrated. The balance of evidence suggests that OFMT may represent a peripheral nerve sheath tumor of low-grade malignancy, although the picture is incomplete.

Allelic loss on chromosome 22Q in epithelioid sarcomas

Epithelioid sarcomas are soft tissue tumors with an indolent, but potentially aggressive, clinical behavior. Distinction from other benign and malignant entities may be a diagnostic dilemma. In this study, we evaluate the presence of loss of heterozygosity (LOH) of chromosome 22q in tumor DNA from 13 epithelioid sarcomas, four epithelioid angiosarcomas, and two epithelioid hemangioendotheliomas, and investigate its possible role in diagnosis. LOH was detected in 6 of 10 (60%) of the informative epithelioid sarcomas. No allele loss was detected in the informative vascular tumors, three angiosarcomas, and two hemangioendotheliomas. Chromosome 22q carries the locus of a tumor suppressor gene, the neurofibromatosis 2 (NF2) gene, which has been shown to be lost or mutated in some NF2-related tumors, sporadic meningiomas, and vestibular schwannomas, as well as a few other tumors. Our data suggest that a region of chromosome 22q may be the locus of a tumor suppressor gene involved in the tumorigenesis of these neoplasms. Genetic alterations of yet-unknown tumor suppressor genes in this region, or even the NF2 tumor suppressor gene, may play a role in epithelioid sarcomas tumorigenesis. The fact that LOH was only detected in epithelioid sarcomas and not in the vascular tumors studied suggests a possible role for this marker in diagnosis.

Elastofibromatous change of the rectum. A lesion mimicking amyloidosis.

We report the case of a 58-year-old woman who had a 7-year history of multiple myeloma and multiple rib fractures and who presented with dysphagia. She underwent thorough gastrointestinal evaluation to rule out the possibility of amyloidosis. Although upper gastrointestinal biopsies were negative, the rectal biopsy was characterized by extensive smudgy eosinophilic deposits in the submucosa that closely resembled amyloid, except that they were not congophilic. Fibers with serrated borders characteristic of those in elastofibroma were identified and confirmed by means of elastic stain and electron microscopy. Elastofibromatous change of the gastrointestinal tract is a rare lesion that has been reported once previously in association with gastric ulcer. This case illustrates that it may occur as a spontaneous or subclinical finding in the absence of other pathologic lesions. The close resemblance between elastofibromatous change and amyloid deposits necessitates the appropriate histochemical and ultrastructural studies.

p53 Mutations and Tumor Progression in Well-differentiated Liposarcoma and Dermatofibrosarcoma Protuberans

Mutations of the tumor suppressor gene p53 have been identified in a wide variety of human tumors, including soft tissue sarcomas. Most missense mutations of p53 increase the half-life of the protein resulting in its accumulation in the nucleus. Immunohistochemical staining with a monoclonal antibody PABI801 (Oncogene Science, Uniondale, NY) detects the intranuclear accumulation of p53 protein in formalin-fixed tissue, and, thus, indicates the presence of missense mutations within the p53 gene. We compared p53 immunoreactivity in paraffin sections of low-grade sarcomas that progressed to high-grade lesions with low-grade sarcomas that had not progressed to high-grade lesions to determine if (1) histologic progression is associated with increasing incidence of p53 missense mutations, and (2) p53 missense mutations within low-grade areas are predictive of which lesions undergo histologic progression. To examine these questions we studied well-differentiated liposarcoma with and without dedifferentiation and dermatofibrosarcoma protuberans with and without areas of fibrosarcoma. Nuclear p53 immunoreactivity was detected in 48% (12/25) of well-differentiated liposarcoma with dedifferentiation compared to only 6% (1/17) of well-differentiated liposarcoma alone. p53 nuclear immunoreactivity was also detected in 25% (4/16) of dermatofibrosarcoma protuberans with fibrosarcoma, and in 0% (0/24) of dermatofibrosarcoma protuberans lacking fibrosarcoma. In cases of well-differentiated liposarcoma with dedifferentiation and dermatofibrosarcoma protuberans with fibrosarcoma displaying immunoreactivity, the staining occurred almost exclusively in the high-grade areas and very infrequently in the low-grade regions as well. We conclude that histologic progression of well-differentiated liposarcoma and dermatofibrosarcoma protuberans is associated with increased nuclear p53 immunoreactivity. Since p53 immunoreactivity occurs infrequently in the low-grade areas of those sarcomas that had transformed to higher grade lesions, it does not appear to be a useful predictor of tumor progression in low-grade lesions. Int J Surg Pathol 3(1):35-42, 1995