Osteosarcomatous Differentiation Research Articles

Phyllodes Tumor with Osteosarcomatous Differentiation: A Comparative Immunohistochemical Study between Epithelial and Mesenchymal Cells

Phyllodes tumor of the breast with osteosarcomatous differentiation is rare and very little is known about its molecular profile. An immunohistochemical panel with 37 primary antibodies including cytokeratins, mesenchymal markers, key regulators of the cell cycle, oncogenes, apoptosis-related proteins, metalloproteinases and their inhibitors was performed on a formalin-fixed paraffin-embedded sample of phyllodes tumor with osteosarcomatous differentiation in a 49-year-old woman. Antiapoptotic stimuli (survivin) predominated in sarcomatous cells. Antiproteolytic stimuli (TIMP-1, TIMP-2 and PAI) were preponderant in all cells, a surprising fact in view of the aggressiveness of the neoplasm. The immunoprofile of the osteoblastic and stromal cells was quite similar, except for c-erbB-3, c-myc, cyclin D1 and p21. Both exhibited positive cells for actin, MyoD1 and GFAP. Our results suggest that this osteosarcoma may have originated from metaplasia of stromal cells that underwent a malignant change.

Osteosarcoma of the breast—an unusual presentation

Cystosarcoma phyllodes is an uncommon primary breast malignancy which undergoes osteosarcomatous differentiation in a small subgroup of patients. Uptake of 99m technetium methylene diphosphonate (99mTcMDP) is known to occur within pulmonary, lymph node and soft tissue metastases arising from osteosarcomas of bone and is related to the presence of osteoid within these tumours. Uptake of 99mTcMDP has also been reported from pulmonary metastasis arising fromosteosarcomasof the breast. Similar uptake would be expected from osteoid elements of the breast sarcoma itself, but this has not been previously documented. We present a case of an osteosarcoma of breast showing up as intense uptake on bone scintigraphy performed for unrelated joint pains. The hot spot seen projected over the right upper chest could not be explained satisfactorily at the time of the study and was thought to represent an artefact. A few weeks later, the patient presented with a breast lump, which was subsequently diagnosed as an osteosarcoma in phyllodes tumour. Retrospectively, the unexplained hot spot on bone scintigraphy corresponded to the site of tumour in the right breast.

Recurrent high-grade leiomyosarcoma with heterologous osteosarcomatous differentiation

Leiomyosarcomas (LM) of the soft tissue comprise approximately 5-10% of all soft tissue sarcomas. Besides the classic LM, several distinctly uncommon features of the cellular and growth patterns of LM have been described. The term "dedifferentiated LM" has rarely been used in the literature to describe soft tissue LM containing areas of undifferentiated, pleomorphic appearance or detectable heterologous differentiation. We report on a case of high-grade LM with almost entire transition to an osteosarcoma, which was classified as recurrent high-grade LM with heterologous osteosarcomatous differentiation. The identification of areas with osteosarcomatous dedifferentiation in soft tissue sarcomas can be of clinical importance because of a possible change in oncologic treatment strategies.

A CASE OF A PLEURAL EFFUSION, CALCIFIED PLEURAL PLAQUES AND AN ABNORMAL BONE SCAN

INTRODUCTION: The annual incidence of malignant mesotheliomas in the United States is 2200 cases per year, of which 70% are linked to asbestos exposure (1). Osteosarcomatous differentiation of this tumor has been reported in 14 cases (2, 3). We report a case of a patient who presented with a large pleural effusion, very densely calcified pleural plaques and an abnormal bone scan.

Pulmonary artery angiosarcoma: a clinicopathologic and radiological correlation

A 69-year-old man presented with cough, shortness of breath, and fatigue. He was initially treated for allergies and then for pulmonary embolism. Radiologically, a tumor mass was found to occlude the right pulmonary artery and involve the pulmonary trunk. A right pneumonectomy was performed. Histologically, a cellular malignant spindle and epithelioid tumor with areas of necrosis and brisk mitotic activity was seen. In some areas, the tumor appeared to form vascular channels. Focal osteosarcomatous differentiation was present. Immunohistochemical studies were performed including vimentin, smooth muscle actin, desmin, CD31, CD34, S100, and pan-cytokeratin. The tumor cells were positive for CD31 and vimentin and negative for pan-cytokeratin, CD34, and S100. Two months after surgery, the patient was alive and well.

Osteogenic pulmonary metastases originating from a phyllodes tumour of the breast with osteosarcomatous differentiation

Malignant phyllodes tumour is an uncommon breast neoplasm which undergoes osteosarcomatous differentiation in 1.3% of cases. We document the plain film, CT and scintigraphic features of a case of pulmonary metastases from this rare primary tumour.

Sarcomatoid variant of salivary duct carcinoma: clinicopathologic and immunohistochemical study of eight cases with review of the literature.

Salivary duct carcinoma (SDC) is an uncommon, high-grade tumor. We present 8 cases of sarcomatoid SDC, which has been defined recently as a rare variant of SDC. The 8 patients (5 men, 3 women) had a mean age of 63.6 years. Histologically, all tumors were characterized by a biphasic neoplasm composed of both SDC and sarcomatoid elements. In 3 cases, sarcomatoid components showed osteosarcomatous heterologous differentiation. A residual pleomorphic adenoma was detected in 5 tumors. The sarcomatoid component showed focal immunoreactivity for cytokeratin in 4 cases and epithelial membrane antigen in all 8 cases. Diffuse p53 immunostaining was detected in 3 cases, and it was coexpressed in both components. Our observations support the histogenetic theory of a common origin of the carcinomatous and sarcomatoid populations. Of the 13 patients, including our 8, reported to have sarcomatoid SDC arising in a major salivary gland and for whom long-term follow-up data were available, 7 have died of disease (mean survival, 15.6 months). These results indicate that sarcomatoid SDC is a highly aggressive tumor, similar to conventional SDC.

Sarcomatoid Variant of Salivary Duct Carcinoma

Salivary duct carcinoma (SDC) is an uncommon, high-grade tumor. We present 8 cases of sarcomatoid SDC, which has been defined recently as a rare variant of SDC. The 8 patients (5 men, 3 women) had a mean age of 63.6 years. Histologically, all tumors were characterized by a biphasic neoplasm composed of both SDC and sarcomatoid elements. In 3 cases, sarcomatoid components showed osteosarcomatous heterologous differentiation. A residual pleomorphic adenoma was detected in 5 tumors. The sarcomatoid component showed focal immunoreactivity for cytokeratin in 4 cases and epithelial membrane antigen in all 8 cases. Diffuse p53 immunostaining was detected in 3 cases, and it was coexpressed in both components. Our observations support the histogenetic theory of a common origin of the carcinomatous and sarcomatoid populations. Of the 13 patients, including our 8, reported to have sarcomatoid SDC arising in a major salivary gland and for whom long-term follow-up data were available, 7 have died of disease (mean survival, 15.6 months). These results indicate that sarcomatoid SDC is a highly aggressive tumor, similar to conventional SDC.

Gliosarcoma with osteosarcomatous differentiation: review of radiological and pathological features

Gliosarcoma is a rare tumor of the central nervous system, consisting of gliomatous and sarcomatous elements. We present an unusual case of gliosarcoma which demonstrated a variation in phenotype over a six month period, changing from a gliosarcoma with osteosarcomatous differentiation, to a gliosarcoma with no osteosarcomatous component. The initial histological diagnosis was glioblastoma multiforme. Fifteen months later the tumor had transformed into a gliosarcoma demonstrating osteosarcomatous differentiation, with the majority of the tumor consisting of osteoid matrix. Further samples taken six months later revealed gliosarcoma with almost no osteosarcomatous component. It is recognized that glioblastoma can undergo a change in phenotype, transforming into a gliosarcoma. This case demonstrates that ongoing changes in phenotype can occur, especially when the tumor has been treated with chemotherapy and radiotherapy. An understanding of the pathological progression of gliosarcoma will become increasingly important as novel treatments for gliosarcoma and glioblastoma become available.

Malignant mesenchymoma of the pleura

Malignant mesenchymomas are rare soft tissue tumors of mesenchymal origin. We report a case of pleural localization with liposarcomatous, leiomyosarcomatous and osteocartilaginous elements. The treatment associated surgical resection, chemotherapy and radiotherapy. Sixteen months after the diagnosis a metastatic retroperitoneal sarcoma with osteosarcomatous differentiation appeared without any sign of thoracic recurrence. A surgical resection was performed, but a rapid retroperitoneal recurrence led to death.

Sarcomatoid renal cell carcinoma with massive osteosarcomatous differentiation: an unusual image in clinical urology

A 46-year-old Hispanic woman presented with a 3-year history of a gradually enlarging right upper quadrant abdominal mass. The serum alkaline phosphatase was 2496 IU/L (normal 13 to 126 IU/L). Computed tomography of the chest, abdomen, and pelvis revealed an enormous, densely calcified mass arising from the kidney with no evidence of metastases (Fig. 1). A bone scan demonstrated increased tracer activity in the area of the mass with no evidence of skeletal metastases (Fig. 2). Radical nephrectomy revealed an almost entirely ossified mass measuring 20.5 cm in its greatest dimension. The histopathologic examination revealed a high-grade malignant neoplasm with extensively calcified osteoid that had features of an osteosarcoma. On electron microscopy, the malignant neoplastic cells showed the presence of desmosomes, indicating epithelial derivation (Fig. 3). On the basis of the electron microscopy findings, the neoplasm was diagnosed as poorly differentiated sarcomatoid renal carcinoma with massive osteosarcomatous differentiation.

Carcinosarcoma of the Colon: Report of a Rare Tumor

Carcinosarcoma is a rare tumor that shows both epithelial and stromal malignant differentiation. Most reported cases of carcinosarcoma affect the female genital tract (and are called malignant mixed müllerian tumors), but there are also some isolated reports of cases affecting the lung and the head and neck area. Carcinosarcomas only rarely affect the gastrointestinal tract, mainly the esophagus. To the best of our knowledge, only eight cases of carcinosarcoma of the colon have been reported to date. For some lesions, the term 'sarcomatoid carcinoma' is preferred to 'carcinosarcoma', as both stromal and epithelial cells have shown cytokeratin expression on immunohistochemistry. The expression 'carcinosarcoma' should be applied only to those lesions, the stromal elements of which do not express epithelial markers. We report a new case of carcinosarcoma affecting the left colon. The most unique feature of this tumor is that it shows chondro-and osteosarcomatous differentiation, a feature that has been described previously in only one colonic carcinosarcoma. We discuss the histopathological and immunohistochemical features of this lesion as well as its possible histogenesis.

A rare case of carcinosarcoma of the maxillary sinus with osteosarcomatous differentiation

A unique case of carcinosarcoma in the maxillary sinus is reported. A 47-year-old man visited our hospital with complaints of right nasal obstruction and bloody rhinorrhea. Examination revealed a hemorrhagic mass with necrosis in the maxillary sinus that infiltrated the right nasal cavity. Histologically, the tumor was composed of both carcinomatous and sarcomatous elements. Nests of squamous cell carcinoma and adenocarcinoma were scattered in the sarcomatous element with osteosarcomatous differentiation. No distinct demarcation between the two elements was observed and some spindle-shaped cells in the sarcomatous component were immunoreactive to epithelial markers by immunohistochemical staining. Although the histogenesis of carcinosarcoma remains unclear, the histologic pattern of the present case indicates the possibility that a multipotential cell, capable of both epithelial and mesenchymal differentiation, was the origin of the rare tumor.

Osteosarcomatous differentiation in phyllodes tumors.

Osteosarcomatous differentiation in phyllodes tumors is uncommon. The clinicopathologic features of 22 such cases in our files were retrospectively reviewed to evaluate the prognostic significance of this rare neoplasm. All patients were women between 40 and 83 years of age (mean, 60 years). Most (73%) presented with a palpable mass. None had prior irradiation to the breast or chest region. Patients were treated with excisional biopsy (N = 4), partial mastectomy (N = 1), or mastectomy (N = 17). All axillary nodes, dissected in 11 patients, were free of tumor. Two patients had extramammary spread at diagnosis. The neoplasms measured 1.9-15 cm (mean, 6.4 cm); 54% were grossly circumscribed or multilobulated. The osteosarcomatous component was classified as fibroblastic (N = 11), osteoclastic (N = 6), or osteoblastic (N = 5) and occupied a variable percentage of the phyllodes' stroma ranging from -25% to essentially 100% of the neoplasm. Of 21 patients with available follow-up, 11 (52%) were alive at a median follow-up of 44 months. Nine patients (43%) developed locally recurrent (N = 1) or metastatic (N = 8) disease. Metastases were clinically apparent within 1 year of diagnosis in all eight patients; seven died within 12 months of detection of initial metastasis. By univariate analysis, gross tumor size and osteosarcoma subtype significantly correlated with prognosis. In a multivariate analysis, neither of these factors were independent prognosticators. Phyllodes tumors with an osteosarcomatous component are potentially aggressive neoplasms, particularly when large (>5 cm) or associated with an osteoclastic or osteoblastic osteosarcoma. Complete excision without axillary dissection is advised.

Malignant phyllodes tumor with chondrosarcomatous differentiation: Report of a case with cytological presentation

Malignant phyllodes tumor is a rare breast tumor with neoplastic epithelial and stromal components. The stromal component may show homologous and heterologous sarcomatous elements, including chondrosarcomatous and osteosarcomatous differentiation. Because these tumors may present with an almost exclusively sarcomatous component, it is important for the pathologist to include this entity in the diagnostic considerations of fine-needle aspirations of breast neoplasms showing sarcomatous differentiation. Following surgical excision, careful examination of the gross specimen and thorough sampling of the specimen is recommended before rendering a definitive histologic diagnosis. We describe the cytologic and histologic findings in a case of malignant phyllodes tumor with sarcomatous overgrowth showing predominantly chondrosarcomatous differentiation. Diagn. Cytopathol. 1999;20:241–245. © 1999 Wiley-Liss, Inc.

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.

Malignant Phyllodes Tumor of the Breast

Phyllodes tumors of the breast are rare lesions that historically have been presumed to be related to fibroadenomata, largely by virtue of the entities' histologic similarities. We report four cases of malignant phyllodes tumors (cystosarcoma phyllodes) of the breast, three showing liposarcomatous differentiation and one showing chondrosarcomatous and osteosarcomatous differentiation, each of which had demonstrable histologic continuity with benign fibroadenomata; one patient had a prior and concurrent history of multiple bilateral fibroadenomata. We postulate that fibroadenomata and phyllodes tumors (benign, borderline, and malignant) may constitute a spectrum of one stromal disease analogous to mammary epithelial hyperplasia, atypical hyperplasia, in situ, and invasive carcinoma. Int J Surg Pathol 3(1):17-22, 1995

Renal Cell Carcinoma with Osteosarcomatous Differentiation Simulating Staghorn Calculus: A Case Report and Literature Review

We report a case of renal cell carcinoma that showed extensive osteosarcomatous differentiation and simulated a staghorn calculus clinically and radiologically. The literature on osteosarcomatous differentiation in renal cell carcinoma is reviewed.

Anaplastic Thyroid Carcinoma with Osteosarcomatous Differentiation

A case of a thyroid tumour with the cytological and histological pattern of anaplastic carcinoma with extensive osteosarcomatous differentiation in a 54-year-old Kaukasian woman is presented. Immunohistochemical examination revealed keratin-vimentin co-expression in anaplastic tumour areas. According to the WHO classification of thyroid tumours the present tumour has to be classified as an anaplastic carcinoma. A retrospective survey revealed only twenty-four comparable cases in the literature. The present tumour most likely represents an example of a neoplastic epithelial-mesenchymal metaplasia. The possible mechanisms of the occurrence of thyroid tumours with mixed epithelial-mesenchymal differentiation are briefly discussed.

Sarcomas of the great vessels. A clinicopathologic study

There are few reports comparing the clinicopathologic features of sarcomas of the aorta (SA), sarcomas of the inferior vena cava (SIVC), and sarcomas of the pulmonary artery (SPA). The authors retrospectively reviewed 11 SA, 16 SIVC, and 16 SPA, and compared clinical, pathologic, and immunohistochemical findings. The mean age at presentation for SA was 62.3 +/- 17.3 years versus 41.3 +/- 17.1 for SPA; mean age for SIVC was 49.9 +/- 18.8. Nine of 11 SA and 14 of 16 SPA were grossly confined to the lumen, compared with only two SIVC. Luminal sarcomas were classified as poorly differentiated (intimal), angiosarcoma or leiomyosarcoma. Eight SA, 13 SPA, and one SIVC were of the intimal type and were composed of fibroblastic or myofibroblastic cells; five had "storiform" areas typical of malignant fibrous histiocytoma, and all had areas of necrosis. Intimal SPA were more likely myxoid than SA, and osteosarcomatous differentiation was present only in SPA (three cases). Intimal sarcomas were negative for desmin, Factor VIII-related antigen, S-100 protein, and CD34/QBend; all were positive for vimentin and most showed positive cells for smooth muscle actin. One luminal SA and one luminal SPA were histologically typical of angiosarcoma. Two SPA, 2 SA, and 14 SIVC were predominantly mural, most of which were leiomyosarcomas. The mean survival of intimal SA was poor (5 months), compared with 37 months for SIVC and 23 months for intimal SPA. SA, SPA, and SIVC differ in their clinical presentation and survival. Most SA and SPA sarcomas are aggressive, probably derived from intimal cells that show myofibroblastic differentiation. SIVC are usually derived from medial smooth muscle and are relatively well differentiated leiomyosarcomas.