Latency-associated nuclear antigen expression and human herpesvirus-8 polymerase chain reaction in the evaluation of Kaposi sarcoma and other vascular tumors in HIV-positive patients.

Human herpesvirus-8 (HHV-8) latency-associated nuclear antigen (LANA) is expressed in endothelial and spindle cells of nearly all Kaposi sarcomas, and the presence of this antigen in serum is strongly correlated with the risk of developing Kaposi sarcoma in immunocompromised individuals. Studies of vascular tumors occurring in the general population show LANA expression to be specific for Kaposi sarcoma. No study to date, however, has examined whether non-Kaposi sarcoma vascular tumors arising in immunocompromised patients may express LANA, possibly reflecting origin from an HHV-8-infected endothelial progenitor cell. The objective of this study was to evaluate the specificity of LANA expression for Kaposi sarcoma in immunocompromised patients by LANA immunohistochemistry and real-time polymerase chain reaction (PCR) for HHV-8. A total of 13 cases of non-Kaposi sarcoma vascular tumors (12 hemangiomas and one epithelioid hemangioendothelioma) and 24 cases of Kaposi sarcoma, all from known HIV-positive patients, were immunostained for LANA and evaluated for the presence of HHV-8 DNA by real-time PCR. LANA expression was seen in 22 of 24 (92%) of Kaposi sarcoma cases and in 0 of 13 non-Kaposi sarcoma cases. Real-time PCR detected HHV-8 in all of the Kaposi sarcoma cases and in four of the non-Kaposi sarcoma cases (all hemangiomas). LANA expression appears to be a highly sensitive and specific marker of Kaposi sarcoma in both the general population and in HIV-positive patients. This is in contrast to HHV-8 PCR, which is positive in a small subset of non-Kaposi sarcoma vascular tumors, most likely due to detection of HHV-8 within intratumoral blood mononuclear cells by the highly sensitive real-time PCR technique. For this reason, LANA immunohistochemistry is preferable to HHV-8 PCR for the evaluation of problematic vascular proliferations in HIV-positive individuals.     

Pigment-free clear-cell sarcoma

Clear-cell sarcoma of tendons and aponeuroses is an infrequent soft tissue sarcoma. Although this sarcoma is now accepted as a clinico-pathological entity and is well-defined clinically, questions on the histogenesis are still under discussion. Because of the possible presence of melanin pigment the idea was put forward that these tumors may be soft tissue melanomas. The authors studied a clear-cell sarcoma without melanin pigment and found at the ultrastructural level that the tumor cells often showed a basal lamina-like material in the vicinity of their cell membranes and were inclined to wrap around extracellular structures. They were in part connected to another by desmosome-like junctions and occasionally contained membrane-bound dense bodies resembling neurosecretory-type granules. Pinocytosis and glycogen were lacking. The results of electron microscopic examination showed this tumour to be closer to the malignant schwannoma rather than melanoma: histogenetically it is obviously linked to the neural crest.     

A comparative study of Kaposi''s sarcoma and granuloma pyogenicum in Uganda

A comparison has been made between two vasoformative lesions, Kaposi's sarcoma and granuloma pyogenicum, as they are encountered in Uganda. Both are predominantly skin lesions arising in the distal extremities, may resemble each other clinically, and are widespread in their distribution in Ugandan communities. They bear a reciprocal relationship to each other as regards age and sex incidence, Kaposi's sarcoma being mainly a disease of adult males and granuloma pyogenicum a disease of immature males and females. Histologically there are many similarities between them, the essential difference being the presence of a spindle-cell sarcomatous element in Kaposi's sarcoma. The clinical behaviour reflects this difference in that granuloma pyogenicum develops quickly and appears to be self-limiting, while Kaposi's sarcoma is slowly progressive and shows much less tendency to regress.On the basis of these findings it is concluded that, although these two lesions may be completely unrelated, it is possible that both represent a response of the vasoformative elements in the skin to a similar form of initiating stimulus and that hormonal or sex-linked genetic factors determine which lesion will develop in response to this stimulus.The presence of intracytoplasmic inclusion in the tumour cells of Kaposi's sarcoma might be of significance in the histogenesis of this tumour, and of value in its histological differentiation from granuloma pyogenicum.     

Translocation involving chromosome 22 in Ewing's Sarcoma. A cytogenetic study of four fresh tumors

Ewing's sarcoma was described in 1921 by James Ewing as a diffuse endothelioma of bone and, for some time, was believed to be an undifferenciated type of Parker's sarcoma. At present, these two entities are thought to be distinct, the macroscopic and microscopic aspects of Ewing's sarcoma being very characteristic, although the exact cell type of this tumor remains unknown. This has lead many workers to study this sarcoma in order to recognize its origin.We thought it of interest to carry out cytogenetic investigations of our cases of Ewing's sarcoma, since very few chromosomal data on this malignancy exist in the literature [1–3].     

Parenchymatous pulmonary endometriosis - metastases of a low-grade endometrial stromal sarcoma?

Based on the data of a case of parenchymatous endometriosis of the lung in which three and a half years later a low-grade endometrial stromal sarcoma of the uterus was diagnosed the origin of this disease is discussed. The follow up of this patient gave the impression that the pulmonary nodules were early metastases of low-grade endometrial stromal sarcoma, which was initially not detected in the routine gynecologic examination. Furthermore, as histological and immunohistochemical examinations are not sufficient to distinguish reliable between endometriosis of the lung and pulmonary metastases from low-grade endometrial stromal sarcoma. In literature, in none of the few cases of parenchymatous pulmonary endometriosis a hysterectomy was performed to exclude a low-grade endometrial stromal sarcoma. Thus, parenchymatous pulmonary endometriosis nodules might be metastases and their occurrence should cause the treating physician to consider a distant metastatic spread from low-grade endometrial stromal sarcoma.     

Myxoid tumor of soft tissue

Focal myxoid change is a well-recognised feature of synovial sarcoma, but the presence of a predominantly myxoid stroma is rare. We describe a new case of myxoid synovial sarcoma in which marked myxoid change initially obscured the diagnosis leading to confusion with malignant peripheral nerve sheath tumor. The patient was a 16 year old man who presented with a left dorsal foot tumor. The diagnosis of synovial sarcoma was suspected on histological and immunohistochemical studies and confirmed with cytogenetic analysis. Recognition of this rare histologic variant of synovial sarcoma is important because it can easily be mistaken for other myxoid spindle cell neoplasms, potentially resulting in suboptimal therapy.     

Monophasic synovial sarcoma–a histological entity?

Consideration is given to the concept of a histologically identifiable monophasic type of synovial sarcoma. It is accepted that a sarcomatous tumour may be encountered where the spindle cells assume a somewhat epithelioid appearance associated with a reticulin pattern unlike that of most other spindle cell sarcomas. The appearance should alert a hsitopathologist to the possibility of a synovial sarcoma and prompt the examination of multiple additional sections in an attempt to find the pathognomonic biphasic pattern. It is not, however, believed that an entire tumour composed of cells of a single type could be identified with certainty as a synovial sarcoma by light microscopy. The term monophasic synovial sarcoma is worthy of retention, but only as a guide towards the establishment of a definite diagnosis by further sampling of the specimen. Other features suggestive of this diagnosis are discussed.     

Mutagen sensitivity as an indicator of soft tissue sarcoma risk.

The etiology of soft tissue sarcoma is poorly understood. Exposure to environmental chemicals may play a role, but the data are not clear. We compared a group of soft tissue sarcoma patients with healthy controls to determine whether the mutagen sensitivity assay, a simple chromosome aberration assay using the radiomimetic bleomycin, might be useful to identify patients at risk for soft tissue sarcoma. Patients with a diagnosis of soft tissue sarcoma at Memorial Sloan-Kettering's outpatient clinic signed informed consent and donated 30 ml of blood. Controls were selected from the general population of Connecticut by random digit dialing. Unrepaired DNA damage was assessed for 100 metaphase spreads for each individual, with the number of breaks in chromatids being counted as breaks per cell (b/c). The 20 cases with soft tissue sarcoma had 1.03 mean b/c and the controls had 0.88 b/c (P = 0.16). Patients with soft tissue sarcoma were 5.7 times more likely to be mutagen sensitive than controls (P = 0.01), as determined after dividing subjects into sensitive or not sensitive groups based on the median b/c among controls. As mutagen sensitivity has been shown to be associated with a number of cancers and appears to reflect genetic susceptibility, this assay may be an appropriate biomarker for radiation sensitivity or it may be a marker of susceptibility to soft tissue sarcoma. Larger studies should be undertaken to assess these possibilities.     

Epitheloides Sarkom

Epithelioid sarcoma represents a rare sarcoma with a poor long-term prognosis that arises predominantly on the distal extremities of young adult patients, often mimicking a benign, non-neoplastic condition. Histologically, epithelioid sarcoma is characterized by a multinodular growth with central necrosis, and the neoplasms are composed of relatively uniform epithelioid tumour cells showing a coexpression of vimentin, epithelial membrane antigen and pancytokeratin, and in about half of the cases of CD34. Interestingly, most cases of epithelioid sarcoma show a loss of INI1, whereas the inactivation of the tumour suppressor gene SMARCB1/INI1 is only rarely caused by mutation. The proximal variant of epithelioid sarcoma is composed of confluent sheets of enlarged epithelioid and rhabdoid tumour cells and represents the morphological progression of this entity. The fibroma-like variant of epithelioid sarcoma as well as the angiomatoid and myxoid variants of epithelioid sarcoma are rare morphological variants and need to be considered in the differential diagnosis of other benign and malignant neoplasms.     

Kaposi's sarcoma and HIV.

Recently published informed debate affords strong indication that in patients with the Acquired Immune Deficiency Syndrome, HIV cannot, directly or indirectly, be the cause of Kaposi's sarcoma. This paper provides reasons for disallowing a current alternative theory that Kaposi's sarcoma is due to an unidentified sexually transmitted infectious agent and proposes instead that Kaposi's sarcoma is the result of prolonged and repeated exposure to nitrites and/or semen. If this alternative hypothesis is strengthened by confirmation of its predictions then the relationship of HIV to Kaposi's sarcoma, one of the principal AIDS-associated diseases, becomes somewhat remote. This may facilitate a shift of emphasis and encourage the development of alternative therapies.     

Kaposi's sarcoma revisited

Kaposi's sarcoma is a puzzling condition of unclear, possibly endothelial origin. It is divided into four distinct types regarding the affected population: classic in elder men of Ashkenazi Jewish and Mediterranean origin; endemic in African infants and young males; iatrogenic in patients under immunosuppressive regimens; epidemic in men having sex with men affected by AIDS. The exact etiopathogenesis of Kaposi's sarcoma continues to elude its researchers. Nonetheless, it has been discovered that human herpesvirus 8 is essential but not sufficient for sarcoma development. Also, iron exposure of populations inhabiting regions with volcanic soils has been suggested to play a pivotal role in the classic and endemic Kaposi's sarcoma etiology. The epidemic Kaposi's sarcoma is strongly associated with HIV's detrimental effect on immune system and HIV's Tat protein proangiogenic properties. Because Kaposi's sarcoma is found also in men having sex with men without AIDS, it has been proposed that certain lifestyle features (e.g. massive semen exposure and inhalant nitrites) may promote transformation of endothelial cells of both lymphatic and vascular origin. Despite numerous studies on Kaposi's sarcoma, it continues to be an incurable disease. The therapeutic approach includes local treatment and systemic administration of cytotoxic, immunomodulator and antiviral drugs. Because of the increasing prevalence of Kaposi's sarcoma, especially in certain parts of Africa, a better understanding of this condition is necessary.     

Symptomatic intracavitary (noninvasive) cardiac metastasis from low grade endometrial stromal sarcoma of the uterus.

We report a 49-year-old woman who was operated upon 33 years ago for uterine endometrial stromal sarcoma of low-grade malignancy. The patient showed obstruction of the right ventricular outflow tract. An echocardiogram and MRI showed that a mass emanating from the inferior vena cava filled the right atrium, the right ventricle, and part of the pulmonary artery. The entire intracavitary neoplasm was successfully removed and diagnosed as low-grade endometrial stromal sarcoma. To our knowledge, this is the second report of a low-grade endometrial stromal sarcoma reaching the heart via the inferior vena cava. In this case an intracavitary metastasis may be a feature indicating the progression of the endometrial stromal sarcoma. Therefore, this neoplasm should be included in the differential diagnosis of cardiac intracavitary neoplasms. Patients affected by this tumor may benefit from early identification and resection of the obstructing neoplasm.     

Uterine leiomyosarcoma with osteosarcomatous dedifferentiation

Leiomyosarcoma is the most common sarcoma of the uterine corpus, however, uterine dedifferentiated leiomyosarcoma remains a poorly characterized entity. Dedifferentiation in leiomyosarcoma can be defined as the occurrence of a high-grade undifferentiated sarcoma in association with a lower-grade sarcoma that demonstrates morphologic and immunophenotypic evidence of myogenic differentiation. The occurrence of extensive heterologous elements in the high-grade area can be problematic confusing the tumor with other more specific types of high-grade sarcomas. Available reports of this entity indicate aggressive biological behavior and poor prognosis. Herein, we describe a case of a 35-year-old woman who presented with menorrhagia and underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. The histopathological examination of the surgical specimen revealed features of a low-grade leiomyosarcoma juxtaposed to a high-grade sarcoma with osteosarcomatous differentiation.     

Herpes virus-like sequences are specifically found in Kaposi sarcoma lesions.

AIM: To detect the prevalence of herpes virus-like DNA sequences in AIDS associated Kaposi sarcoma (KSHV) lesions and normal tissue. METHODS: KSHV detection was performed by polymerase chain reaction (PCR) using four different sets of primers. PCR products were cloned, sequenced, and analysed. RESULTS: All of four biopsies of Kaposi sarcoma lesions and all of three paraffin embedded Kaposi sarcoma tissues were positive for KSHV, while normal tissue from the same patients was negative. Sequence analysis of amplification products revealed polymorphisms that result in amino acid changes of the predicted sequence. CONCLUSIONS: KSHV is prevalent in tissues from Kaposi sarcoma, suggesting a role in the development of the tumour. On this basis, anti-herpes virus agents should be considered to control Kaposi sarcoma.     

Small cell osteosarcoma with Ewing sarcoma breakpoint region 1 gene rearrangement detected by interphase fluorescence in situ hybridization

Because of its characteristic morphologic appearance, small cell osteosarcoma (SCO) can be confused with other small round cell malignancies of the bone, most importantly with Ewing sarcoma, making this distinction difficult. A specific tool used in separating SCO from Ewing sarcoma has been the detection of Ewing sarcoma breakpoint region 1 (EWSR1) gene rearrangements in Ewing sarcoma and their absence in SCO. However, there are rare case reports that have documented the existence of EWSR1 gene rearrangement in SCO. In this report, we describe another case of SCO with an EWSR1 gene rearrangement detected by interphase fluorescence in situ hybridization. Our finding adds support to the existing evidence that SCO is a tumor that can be characterized by EWSR1 gene arrangements. Therefore, we caution the pathology community not to rely solely on molecular studies in distinguishing SCO from Ewing sarcoma.     

Follicular dendritic cell sarcoma presenting as a submucosal tumor of the stomach

Follicular dendritic cell (FDC) sarcomas, especially those of extranodal origin, are extremely rare, and this entity could easily be missed without a high index of suspicion. We report a case of FDC sarcoma presenting as a submucosal tumor of the stomach in a 45-year-old man. The mass was a spindle and epithelioid mesenchymal tumor with many individually scattered and perivascular aggregates of lymphocytes. Immunohistochemical and ultrastructural studies confirmed the diagnosis. Although more than 50 cases of this tumor have been documented in the English literature, to our knowledge the presentation of FDC sarcoma as a submucosal tumor of the stomach has never been recorded. This case highlights the occurrence of FDC sarcoma as a submucosal tumor of the gastrointestinal tract. We believe that FDC sarcoma should be included in the differential diagnosis of spindle or epithelioid cell tumors of the gastrointestinal hollow viscus to prevent this still under-recognized tumor from being overlooked.     

Follicular dendritic cell sarcoma: a rare tumor presenting as an abdominal mass

Follicular dendritic cell (FDC) sarcoma is a rare and probably even underreported entity. Only approximately some 50 cases have been described in the literature, the majority of which had a lymph node origin. The authors report a case of FDC sarcoma arising within the soft tissues of the abdominal cavity. As FDC markers are often not routinely included in antibody panels, awareness of this sarcoma is important, as it can be confused with other tumors, especially when occurring extranodally.     

Immunostaining for SYT protein discriminates synovial sarcoma from other soft tissue tumors: analysis of 146 cases.

Synovial sarcoma in its classic biphasic form can be distinguished readily from other soft tissue lesions; however, monophasic and poorly differentiated forms are diagnostically more problematic. For this reason, we assessed the efficacy of immunostaining for SYT and SSX1 proteins, the gene products resulting from unique synovial sarcoma translocation, to distinguish synovial sarcoma from other soft tissue lesions. A total number of 146 cases were analyzed, including 47 synovial sarcoma cases (all of which were verified by FISH to have t(X; 18) translocation and SYT-SSX fusion gene) and 99 soft tissue tumors of various types. A polyclonal IgG antibody against SYT was used to stain formalin-fixed paraffin embedded tissues. Forty-one out of 47 (87%) synovial sarcoma displayed strong positive nuclear staining (ranging from 80 to 90% of the tumor cells) for SYT antibody. Nineteen of 99 (19%) non-synovial sarcoma cases showed variable nuclear and cytoplasmic staining with SYT, which ranged from 20 to 60% of tumor nuclei, and included malignant peripheral nerve sheath tumor (5/25), solitary fibrous tumor (2/14), Ewing sarcoma (2/6), low grade fibromyxoid tumor (2/4), extraskeletal mesenchymal chondrosarcoma (2/6), gastrointestinal tumor (4/17), epithelioid sarcoma (2/2). The remaining non-synovial sarcomas were negative. This is the first study demonstrating SYT protein expression in tissue sections of synovial sarcoma. This method could provide an easy, rapid and widely applicable means of assisting in the diagnosis of synovial sarcoma, particularly when material and/or resources are unavailable for PCR or FISH-based testing. However, as variable weak staining for SYT may be encountered in a small percentage of non-synovial sarcoma sarcomas, a positive interpretation should be made only when the staining is strong, nuclear and present in the majority of cells.     

Pseudosarcoma in Paget's disease of bone

The appearance of a sarcoma of bone is a well-recognized complication of Paget's disease. The most common type of such a sarcoma is osteosarcoma. Much less common are soft tissue lesions adjoining the pagetic bone that clinically and radiologically simulate sarcoma but histologically represent exaggerated periosteal bone formation as a manifestation of the basic pathologic process. We present a case of a bulky juxtacortical soft tissue mass in the thigh arising from a pagetic femur in a 62-year-old patient with polyostotic Paget's disease that was clinically and radiologically suspected to be a juxtacortical osteosarcoma. Microscopically, the lesion showed features of florid Paget's disease without any evidence of sarcomatous growth. It is important to be aware of this rare manifestation of Paget's disease to avoid unnecessary overtreatment.