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Background
Most soft tissue sarcomas have a tendency to metastasize to the lungs, via blood borne dissemination. This sarcoma is one of the few that tends to metastasize to the brain. Sometimes, these metastasis occur has long as 30 years following the discovery of the original tumor. This sarcoma has undergone a number of name changes ranging from malignant organoid granular cell myoblastoma and malignant nonchromaffin paraganglioma, to its current designation. Part of the confusion stems from the difficulty in assigning a cell of origin for this tumor. In recent years, pathologists have shown this tumor to be a variant of a rhabdomyosarcoma, a sarcoma of skeletal muscle.
OUTLINE
PATHOGENESIS CHARACTERIZATION Chromosome rearrangement at 17q25 and xp11.2 in alveolar soft-part sarcoma: A case report and review of the literature.
Joyama S, Ueda T, Shimizu K, Kudawara I, Mano M, Funai H, Takemura K, Yoshikawa H.
Department of Orthopedic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
Cancer 1999 Oct 1;86(7):1246-50 Abstract quote
BACKGROUND: Despite the characteristic histopathologic appearance of alveolar soft-part sarcoma (ASPS), its histogenesis remains unclear, and cytogenetic analysis of ASPS is limited to eight cases so far because of the extreme rarity of this disease.
METHODS: The authors document a cytogenetic study of a primary case of ASPS in which a modern spectral karyotyping technique was used.
RESULTS: A standard cytogenetic analysis of the primary tumor cells with G-banding revealed 46,XY, add(17)(q25) in 23 of 25 metaphases analyzed. This structural rearrangement of chromosome 17, involving band q25, was also present in 5 of 8 ASPS cases in the literature. Moreover, with the spectral karyotyping technique, the additional part of the long arm of chromosome 17 in the current case was found to originate from chromosome X, resulting in a final tumor karyotype of 46, XY, add(17)(q25).ish der(17)t(X;17) (p11.2;q25)(wcpX+).
CONCLUSIONS: This case report documents a clonal chromosome abnormality of der(17)t(X;17)(p11.2;q25) in ASPS. The results of the current study indicate that further molecular analyses focused on 17q25 and Xp11.2 are of interest and could help to elucidate the pathogenesis of ASPS
APC and beta-catenin in alveolar soft part sarcoma (ASPS)--immunohistochemical and molecular genetic analysis.
Kuhnen C, Herter P, Monse H, Kahmann S, Muehlberger T, Vogt PM, Steinau HU, Muller KM, Muller O.
Institute of Pathology, University Hospital Bergmannsheil, Bochum, Germany
Pathol Res Pract 2000;196(5):299-304 Abstract quote
Apart from its role in cell-adhesion, beta-catenin is regarded as an oncoprotein, the cytoplasmic level of which is regulated by APC as a tumor suppressor protein. Changes of chromosome 5q, the region that includes the APC-gene, are known to be important in the pathogenesis of fibromatosis; however, little is known about the significance of APC and beta-catenin in other mesenchymal tumors.
Therefore, we used immunohistochemistry and DNA-analysis to investigate four cases of alveolar soft-part sarcoma (ASPS) as a mesenchymal tumor with a distinct histologic appearance. In three cases of ASPS the APC-gene product was found to have strong nuclear expression and only faint cytoplasmic staining. Beta-catenin showed a partly membranous, partly strong intracytoplasmic expression. No gene mutations for APC and beta-catenin were detected in any of the four cases.
These investigations suggest that, apart from their function in carcinogenesis and fibromatoses, APC and beta-catenin play a role in the pathogenesis of soft tissue tumors such as ASPS. The significance of a striking nuclear accumulation of non-mutated, virtually functionally active APC-tumor suppressor protein has not yet been investigated. A nuclear function of APC in ASPS in down-regulating nuclear transcription processes linked to overexpression of beta-catenin, as is known in colorectal carcinogenesis, may be hypothesized.
The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25.
Ladanyi M, Lui MY, Antonescu CR, Krause-Boehm A, Meindl A, Argani P, Healey JH, Ueda T, Yoshikawa H, Meloni-Ehrig A, Sorensen PH, Mertens F, Mandahl N, van den Berghe H, Sciot R, Cin PD, Bridge J.
Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021, USA.
Oncogene 2001 Jan 4;20(1):48-57 Abstract quote
Alveolar soft part sarcoma (ASPS) is an unusual tumor with highly characteristic histopathology and ultrastructure, controversial histogenesis, and enigmatic clinical behavior. Recent cytogenetic studies have identified a recurrent der(17) due to a non-reciprocal t(X;17)(p11.2;q25) in this sarcoma.
To define the interval containing the Xp11.2 break, we first performed FISH on ASPS cases using YAC probes for OATL1 (Xp11.23) and OATL2 (Xp11.21), and cosmid probes from the intervening genomic region. This localized the breakpoint to a 160 kb interval. The prime candidate within this previously fully sequenced region was TFE3, a transcription factor gene known to be fused to translocation partners on 1 and X in some papillary renal cell carcinomas. Southern blotting using a TFE3 genomic probe identified non-germline bands in several ASPS cases, consistent with rearrangement and possible fusion of TFE3 with a gene on 17q25. Amplification of the 5' portion of cDNAs containing the 3' portion of TFE3 in two different ASPS cases identified a novel sequence, designated ASPL, fused in-frame to TFE3 exon 4 (type 1 fusion) or exon 3 (type 2 fusion). Reverse transcriptase PCR using a forward primer from ASPL and a TFE3 exon 4 reverse primer detected an ASPL-TFE3 fusion transcript in all ASPS cases (12/12: 9 type 1, 3 type 2), establishing the utility of this assay in the diagnosis of ASPS. Using appropriate primers, the reciprocal fusion transcript, TFE3-ASPL, was detected in only one of 12 cases, consistent with the non-reciprocal nature of the translocation in most cases, and supporting ASPL-TFE3 as its oncogenically significant fusion product. ASPL maps to chromosome 17, is ubiquitously expressed, and matches numerous ESTs (Unigene cluster Hs.84128) but no named genes. The ASPL cDNA open reading frame encodes a predicted protein of 476 amino acids that contains within its carboxy-terminal portion of a UBX-like domain that shows significant similarity to predicted proteins of unknown function in several model organisms.
The ASPL-TFE3 fusion replaces the N-terminal portion of TFE3 by the fused ASPL sequences, while retaining the TFE3 DNA-binding domain, implicating transcriptional deregulation in the pathogenesis of this tumor, consistent with the biology of several other translocation-associated sarcomas.
Cytogenetic abnormalities of alveolar soft-part sarcomas using interphase fluorescent in situ hybridization: trisomy for chromosome 7 and monosomy for chromosomes 8 and 18 seem to be characteristic of the tumor.
Tornoczky T, Kalman E, Sapi Z, Orosz Z, Pajor L.
Department of Pathology, Faculty of General Medicine, Pecs University of Sciences, Hungary
Virchows Arch 2001 Feb;438(2):173-80 Abstract quote
Four alveolar soft-part sarcomas were investigated by means of standard immunohistochemistry and interphase cytogenetics to further characterize the immunophenotype and proliferative activity of this tumor.
The main goal of this study was to explore the chromosomal changes of this rare soft-tissue sarcoma. One epithelial (KLI), three neurogenic [neuron specific enolase (NSE), PGP 9.5, and S100], and five myogenic (desmin, myoglobin, alpha-smooth mnuscle actin, alpha-sarcomeric actin, and MyoD1) markers were used for the immunophenotypical analysis. Proliferative activity was assessed using the Ki67 index. Twelve (peri)centromeric (1, 3, 4, 6, 7, 8, 10, 12, 15, 17, 18, and X) and one telomeric (17q25-qtel.) chromosomal probes were used for interphase cytogenetic analysis. Three of the cases showed cytoplasmic desmin and/or myoglobin, and one showed smooth muscle actin positivity. All of the four tumors had granular, cytoplasmic, possibly nonspecific MyoD1 and sarcomeric actin positivity. Two of the tumors were positive for vimentin, four gave focal and weak staining with neurogenic markers (four of four NSE, one of four S100, and four of four PGP 9.5), but none of them was positive with KLI.
Alveolar soft-part sarcomas may show myogenic immunophenotype in a number of cases, which supports myogenic differentiation. Fluorescent in situ hybridization using alpha satellite chromosomal probes revealed significant alterations in all of the cases. Most frequent and repeated numerical changes, which seem to be characteristic of the neoplasm and may play an important part in its pathogenesis and/or progression, were trisomy 7, monosomy 8 and monosomy 18.
LABORATORY/RADIOLOGIC/
OTHER TESTSCHARACTERIZATION RADIOLOGIC Alveolar soft part sarcoma: MR and angiographic findings.
Suh JS, Cho J, Lee SH, Shin KH, Yang WI, Lee JH, Cho JH, Suh KJ, Lee YJ, Ryu KN.
Department of Diagnostic Radiology, College of Medicine Yonsei University, Seoul, Korea.
Skeletal Radiol 2000 Dec;29(12):680-9 Abstract quote
OBJECTIVE: To present the MR and angiographic findings of alveolar soft part sarcoma (ASPS).
DESIGN AND PATIENTS: MR examinations (12 tumors of 10 patients) of ASPS performed at multiple hospitals were retrospectively reviewed. The tumors were found in the thigh (n=4), lower leg (n=4), femur (n=2, local metastasis), scalp (n=1) and arm (n=1). The MR signal characteristics including signal intensity, homogeneity and signal void of lesions and bony invasion including direct invasion or local metastasis were evaluated. Angiographic findings (n=4) and post-embolotherapy follow-up MR imaging (n=2) findings were also assessed.
RESULTS: Local bony metastasis was found in two cases. Seven tumors showed heterogeneous high signal intensity on T - and T2-weighted images with good enhancement. One tumor had a very high signal on T1-weighted images. Eight tumors (67%) showed numerous signal voids in or near the tumors. All four angiographic studies showed numerous enlarged vessels, arteriovenous shunts and delayed washout. Two cases mimicked arteriovenous malformations on angiographic studies but MR images demonstrated solid soft tissue components as well as tortuous vessels.
CONCLUSIONS: High signal on T1 -weighted image and numerous signal voids are highly suggestive of ASPS, although they are not universal as has been suggested and arteriovenous malformation should be included in the differential diagnosis. Local bony metastases in ASPS were seen in two cases and should be carefully investigated.
Alveolar soft-part sarcoma: a rare soft-tissue malignancy with distinctive clinical and radiological features.
Pang LM, Roebuck DJ, Griffith JF, Kumta SM, Metreweli C.
Department of Diagnostic Radiology and Organ Imaging, Chinese University of Hong Kong.
Pediatr Radiol 2001 Mar;31(3):196-9 Abstract quote
Alveolar soft-part sarcoma (ASPS) is a rare tumour. Certain distinctive clinical and radiological features suggest the correct diagnosis. There is moderate predilection for young women. ASPS almost always arises in skeletal muscle and occurs most frequently in the lower limbs. There is often a long clinical history and a large mass at presentation.
Two young females with ASPS presented with very vascular tumours in the thigh, with prominent intra- and extra-tumoural blood vessels. The imaging findings and the existing literature are reviewed.
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION GENERAL VARIANTS Alveolar soft part sarcoma of the head and neck. A disease of children and young adults.
Simmons WB, Haggerty HS, Ngan B, Anonsen CK.
Division of Otolaryngology - Head and Neck Surgery, Stanford University Medical Center, CA 95305-5328.
Int J Pediatr Otorhinolaryngol 1989 May;17(2):139-53 Abstract quote
Alveolar soft part sarcoma (ASPS) is a rare malignancy of uncertain histologic origin that predominantly afflicts female children and young adults. Forty-three cases occurring in the head and neck have been identified, to which we add a case. The most frequent sites of occurrence in the head and neck are orbit and tongue. Treatment is universally surgical, with limited roles for adjuvant radiotherapy and chemotherapy. Representative populations of patients with orbital, non-orbital and extremity ASPS are compared statistically. Improved disease-free intervals in orbital ASPS vs non-orbital ASPS and head and neck ASPS vs extremity ASPS are documented. Debate exists regarding the histologic origin of ASPS.
The additional case presented does not corroborate recent immunohistochemical studies suggesting myogenic origin. Nevertheless, the clinical pattern of disease offers additional support to the myogenic hypothesis of histologic origin.
Alveolar soft-part sarcoma of the female genital tract: a report of nine cases and review of the literature.
Nielsen GP, Oliva E, Young RH, Rosenberg AE, Dickersin GR, Scully RE.
James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Int J Gynecol Pathol 1995 Oct;14(4):283-92 Abstract quote
Nine alveolar soft-part sarcomas of the female genital tract (four previously reported) occurred in patients 14-38 (mean 29) years of age.
The most common clinical presentation was abnormal uterine bleeding. Two tumors were located in the vagina, three in the cervix or lower uterine segment, three in the uterine corpus, and one in the broad ligament.
The tumors were solid and well circumscribed, ranging in maximum dimension from 1 to 9.8 (average 3.6) cm and had the characteristic histologic features of alveolar soft-part sarcoma. Granules that were diastase resistant and positive by periodic acid-Schiff (PAS) were present in all the tumors, and PAS-positive, diastase-resistant crystals were present in eight of them.
Follow-up information ranging from 9 months to 17 years (average 62 months) was available for all the patients. One patient died of metastatic disease 25 months after diagnosis; eight other patients had uneventful follow-up periods ranging from 9 months to 17 years (average 67 months). The differential diagnosis of these tumors is discussed and the literature reviewed.
Primary alveolar soft-part sarcoma of the mediastinum: a clinicopathological and immunohistochemical study of two cases.
Flieder DB, Moran CA, Suster S.
Department of Pulmonary and Mediastinal Pathology, Armed Forces Institute of Pathology, Washington DC.
Histopathology 1997 Nov;31(5):469-73 Abstract quote
AIMS: Primary alveolar soft part sarcomas originating within the thoracic cavity are rare. The cases herein described highlight the ubiquitous distribution of this neoplasm and the importance of considering this tumour in the differential diagnosis of mediastinal tumours.
METHODS AND RESULTS: Two cases of alveolar soft-part sarcoma of the mediastinum are presented. The patients are two men of 22 and 23 years of age. Clinically, the patients presented with symptoms of chest pain. One tumour was in the anterior mediastinum while the second tumour was in the posterior mediastinum. Even though the bulk of the tumours were in mediastinal locations, both patients had pulmonary metastases at the time of diagnosis. Histologically, both tumours showed the classic morphology of alveolar soft part sarcoma, i.e. a proliferation of large polygonal cells with round to oval nuclei, prominent nucleoli and moderate amounts of eosinophilic cytoplasm arranged in a prominent alveolar pattern. Periodic acid-Schiff stains showed the characteristic diastase-resistant intracytoplasmic crystals. Immunohistochemical studies showed focal myoglobin reactivity in one case, while cytokeratin, vimentin, S100 protein, chromogranin, synaptophysin, neurofilaments, leu-enkephalin, desmin, smooth muscle actin and muscle-specific actin were negative in both cases. The patient with the anterior mediastinal tumour died of disease 14 months after diagnosis, and the patient with the posterior mediastinal mass remained well for at least 15 years and was later lost to follow-up.
CONCLUSIONS: As has been observed in other anatomic areas, namely soft tissues, alveolar soft part sarcomas may follow an uncertain natural history. Interestingly, in our cases, the tumour in the anterior mediastinum followed a fatal course raising the possibility that the anatomic location of the tumour may have play a role in the behaviour of the tumour.
Alveolar soft part sarcoma of the uterine corpus. Report of two cases and review of the literature.
Radig K, Buhtz P, Roessner A.
Department of Pathology, Otto-von-Guericke-University, Magdeburg, Germany.
Pathol Res Pract 1998;194(1):59-63 Abstract quote
Alveolar soft-part sarcoma (ASPS) is a rare tumor of uncertain histogenesis, mainly localized in the extremities and less frequently found in the head, neck and trunk.
The present report describes two cases of ASPS localized in the uterus. In general, this entity is very rarely encountered in the female genital tract. Including the two cases presented here, 27 patients have been described in the literature. Whereas the prognosis for ASPS in soft tissues is usually poor (most of the patients died of lung metastases), those localized in the female genital tract are associated with a much better survival. This could be explained by the fact that their diameter seldom exceeds 5 cm, the size which is regarded as being the critical prognostic limit.
Histologically, both tumors showed the same characteristics as known for ASPS in other localizations: organoid or nest-like arrangement of tumor cells; rounded or polygonal cells with cytoplasm of varying density; thin-walled, sinusoidal vascular spaces between tumor cell nests. Immunohistochemically, we found positivity for desmin and, to a lesser extent, for vimentin. Cytokeratin was negative, which is important in differential diagnosis to other rare uterine neoplasias like clear cell (mesonephroid) adenocarcinomas or metastases.
Primary alveolar soft part sarcoma of bone.
Park YK, Unni KK, Kim YW, Han CS, Yang MH, Wenger DE, Sim FH, Lucas DR, Ryan JR, Nadim YA, Nojima T, Fletcher CD.
Department of Pathology, College of Medicine, Kyung Hee University, Seoul, South Korea.
Histopathology 1999 Nov;35(5):411-7 Abstract quote
AIMS: Alveolar soft part sarcoma is a distinct, rare soft tissue tumour occurring primarily within the skeletal muscles or musculofascial planes in young adults. Primary involvement of bone is extremely rare. We report on six patients with alveolar soft part sarcoma occurring primarily in bone.
METHODS AND RESULTS: Thorough clinical and radiographic examinations were done to rule out any other primary site. The patients were four women and two men aged 17-35 years (mean, 24.5 years). The primary site of the tumour was the femur in three patients, the ilium in one and the fibula in two. In one of the patients with fibular involvement, the tibia was also involved by direct extension. Of the long bone lesions, three were centred in the metaphysis and one in the diaphysis. Radiographically, all of the lesions demonstrated an osteolytic pattern of bone destruction with ill-defined margins and a wide zone of transition between the lesion and adjacent normal bone. Microscopically, all tumours showed the typical histological pattern of alveolar soft part sarcoma. Diastase-resistant, periodic acid-Schiff-positive crystalline structures were identified within the cytoplasm and confirmed ultrastructurally. Immunohistochemically, a keratin stain was negative in all cases; there was positive staining for MyoD1 in the cytoplasm but not the nuclei. Distant metastasis developed in four patients; one died.
CONCLUSION: Alveolar soft part sarcoma arising in bone is extraordinarily rare but should be considered in the differential diagnosis of metastatic hypernephroma in a young patient.
Primary alveolar soft part sarcoma of the stomach: a case report and review.
Yaziji H, Ranaldi R, Verdolini R, Morroni M, Haggitt R, Bearzi I.
Department of Pathology, University of Washington, Seattle, USA.
Pathol Res Pract 2000;196(7):519-25 Abstract quote
Alveolar soft part sarcoma (ASPS) is a rare tumor typically located in skeletal muscles and muscolofascial planes. Isolated cases of ASPS have been described as arising in the viscera.
We report a mesenchymal tumor of the stomach in a 54-year-old Italian woman without evidence of primary neoplasm elsewhere ten years following the initial diagnosis.
The histologic, histochemical, immunohistochemical, and electron microscopic findings were all consistent with the diagnosis of ASPS and allowed differentiating it from morphologically similar and more common tumors, such as metastatic renal cell carcinoma and paraganglioma. The patient is alive and well ten years following the initial presentation.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL PAS positive crystalline inclusions-These characteristic needle-like structures are present within the cytoplasm of the tumor cells producing a reliable diagnostic marker. Alveolar soft-part sarcoma. A study of 13 typical examples and one with a histologically atypical component.
Evans HL.
Cancer 1985 Feb 15;55(4):912-7 Abstract quote
Thirteen cases of typical alveolar soft-part sarcoma and one in which the tumor had a histologically atypical component are presented.
The atypical zone in the latter case was characterized by increased nuclear hyperchromatism and pleomorphism, increased nuclear-cytoplasmic ratio, decreased cytoplasmic eosinophilia and granularity, a less distinct "nesting" pattern, and more numerous mitotic figures. The tumors occurred almost entirely in the younger decades and involved a variety of soft tissue sites. Sex distribution was 1:1, and there was a slight left-sided predominance in tumor location. Median survival of the patients with typical alveolar soft-part sarcoma was 79 months (the patient with the atypical neoplasm died at 36 months).
The major factor related to both survival and the likelihood of metastasis was tumor size.
Alveolar soft part sarcoma: review of nine cases including two cases with unusual histology.
Jong R, Kandel R, Fornasier V, Bell R, Bedard Y.
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
Histopathology 1998 Jan;32(1):63-8 Abstract quote
AIM: Alveolar soft part sarcoma is a very rare tumour. Nine cases are reviewed in order to identify new aspects of this tumour.
METHODS AND RESULTS: The clinical course, histological, immunohistochemical and ultrastructural features of nine cases of alveolar soft part sarcoma were reviewed. Proliferative activity and p53 protein accumulation were assessed immunohistochemically. The patients were aged between 18 and 70 years. In the cases with sufficient follow-up, survival was variable with two patients dying within 5 months and four alive at 4 years. Histologically all tumours had an alveolar component but one case also had a spindle component and another case had a pseudoglandular pattern. Six cases showed desmin immunoreactivity, one was muscle-specific actin positive, two were positive for S100 protein and three were positive for vimentin. MIB-1 immunostaining was seen in up to 35% of cells. Two cases showed p53 protein accumulation.
CONCLUSIONS: There appeared to be no correlation between short term survival (4 years or less) and clinical presentation, adjuvant treatment, tumour size, histological grade, vascular invasion by tumour, proliferative index, or p53 protein accumulation. Although unusual, spindle cell or pseudoglandular components can be seen in alveolar soft part sarcoma.
SPECIAL STAINS/
IMMUNOPEROXIDASE/
OTHERCHARACTERIZATION SPECIAL STAINS PAS stain highlights the intracytoplasmic crystalline array Alveolar soft part sarcoma: a report of two cases with some histochemical and ultrastructural observations.
Ekfors TO, Kalimo H, Rantakokko V, Latvala M, Parvinen M.
Cancer 1979 May;43(5):1672-7 Abstract quote
In a survey of all malignant soft tissue tumors in the extremities and limb girdles in Finland between 1960 and 1969, only one alveolar soft part sarcoma was found among 246 tumors (0.4%). Another alveolar soft part sarcoma, diagnosed in 1976, was more thoroughly studied. There was evidence that the characteristic crystals of alveolar soft part sarcoma are formed from the dense granules. Both were PASM-positive at ultrastructural level. No monoamines were detected in the cells by formaldehyde-induced fluorescence. This is a further fact to nullify the theory of the paraganglionic origin of alveolar soft part sarcoma, but the question of the histogenesis of the tumor still remains open.
Alveolar soft part sarcoma: an analysis of 8 cases. Review of the literature.
Szklarski W, Wasilewska A, Gruchala A, Rys J, Jaworska A, Kruczak A, Niezabitowski A.
Department of Tumour Pathology, Center of Oncology, Krakow.
Patol Pol 1991;42(1):33-8 Abstract quote
Eight cases of alveolar soft part carcinoma (ASPS) are presented.
The average age of the patients was 28 years. There were 6 women and 2 men. The left sided and right sided tumours were equal in number. Local recurrence was not observed in any of the patient treated, but lung metastases occurred in 6 of them. Three patients died with disease the average 35 months after treatment. Histologically in one case the uniform sheets of cells were observed without alveolar arrangement.
The presence of beta glucuronidase (BG), acid phosphatase (AP) and non specific esterase (NE) in tumor cells was seen in one case studied. Immunohistochemical and ultrastructural examination confirm the thesis, that ASPS consist a distinct clinico-morphologic entity, the histogenesis of which remains uncertain.
IMMUNOPEROXIDASE
*Department of Pathology and Laboratory Medicine daggerEmory University School of Medicine, Atlanta, GA double daggerPortuguese Institute of Oncology, Lisbon, Portugal section signHospital do Divino Espirito Santo-Ponta Delgada-Azores, Portugal
Alveolar soft-part sarcoma (ASPS) is a rare, clinically, morphologically, ultrastructurally, and cytogenetically distinctive malignant mesenchymal tumor that most classically occurs in the extremities of adolescents and young adults, but has also been described in a number of unusual sites. The molecular signature of ASPS is a specific der(17)t(X;17)(p11.2;q25) translocation, which results in the fusion of TFE3 transcription factor gene (from Xp11) with ASPL at 17q25. The ASPL-TFE3 fusion protein encoded by the fusion transcript can be detected immunohistochemically with commercially available antibodies to the carboxy terminus of TFE3.
Herein, we report a unique case of ASPS presenting in the bladder with subsequent urethral recurrence in a 25-year-old woman. We emphasize the differential diagnoses engendered by ASPS including common, not-so-common, and rare tumors involving the urinary bladder that have a nested architecture, and both clear and eosinophilic cytoplasm, and demonstrate the utility of a broad immunohistochemistry panel including TFE3 for diagnosis.Immunohistochemical profile of myogenin and MyoD1 does not support skeletal muscle lineage in alveolar soft part sarcoma.
Gomez JA, Amin MB, Ro JY, Linden MD, Lee MW, Zarbo RJ.
Department of Pathology, Henry Ford Hospital, Detroit, MI 48202-2689, USA.
Arch Pathol Lab Med 1999 Jun;123(6):503-7 Abstract quote
BACKGROUND: The histogenesis of alveolar soft part sarcoma remains elusive. Myogenic origin is favored, although conflicting data on immunohistochemical demonstration of muscle-associated markers exist. Myogenin and MyoD1, transcription factors of the myogenic determination family, have crucial roles in commitment and differentiation of mesenchymal progenitor cells to myogenic lineage and in maintenance of skeletal muscle phenotype. Their immunohistochemical detection is specific in characterization of rhabdomyosarcoma.
METHODS: Antibodies for myogenin, MyoD1, desmin, and muscle-specific actin were employed on a large series of cases (n = 19) of formalin-fixed, paraffin-embedded alveolar soft part sarcoma.
RESULTS: Minimal scattered nuclear staining was seen with myogenin. All cases had pronounced, nonspecific granular cytoplasmic immunostaining with MyoD1; nuclei were negative. All tumors were negative for desmin and muscle-specific actin. Ultrastructural study in 10 cases failed to reveal features of skeletal muscle differentiation.
CONCLUSIONS: Cytoplasmic staining with MyoD1 in alveolar soft part sarcoma may correspond to cross-reactivity with an undetermined cytoplasmic antigen. The lack of immunostaining with myogenin, MyoD1, desmin, and muscle-specific actin provides evidence against a myogenic origin for alveolar soft part sarcoma.
ULTRASTRUCTURE Crystal-deficient alveolar soft part sarcoma.
Tucker JA.
Department of Pathology, University of South Alabama, Mobile.
Ultrastruct Pathol 1993 May-Aug;17(3-4):279-86 Abstract quote
lassically, ultrastructural examination of alveolar soft part sarcoma reveals large, dramatic, rhomboid to needlelike crystals with a characteristic substructure.
In this study of four cases of alveolar soft part sarcoma, only two exhibited large crystals, which were rare. All four cases, however, exhibited round, electron-dense granules, and in the two cases without large crystals these granules rarely exhibited elongation with the characteristic substructure of alveolar soft part sarcoma that permits definitive diagnosis. Two of these cases had been previously studied at other institutions, where crystals were not identified ultrastructurally and electron microscopy was considered noncontributory.
Large crystals, then, may be rare or absent in alveolar soft part sarcoma. Careful search may be necessary to find granules with the characteristic periodic substructure.
Alveolar soft-part sarcoma: a review of the pathology and histogenesis.
Ordonez NG, Mackay B.
University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Ultrastruct Pathol 1998 Jul-Aug;22(4):275-92 Abstract quote
The descriptive designation, alveolar soft-part sarcoma, continues to be used for this uncommon soft-tissue malignancy because an acceptable hypothesis for its histogenesis has not been advanced, despite studies with electron microscopy and immunohistochemistry. These techniques have, nevertheless, provided significant information that is useful in the differential diagnosis of the tumor and pertinent in speculation concerning its nature. The most intriguing ultrastructural feature is the secretory process that culminates in the formation of the distinctive cytoplasmic crystals.
Myogenic differentiation has been favored in a number of recent reports on the basis of immunohistochemical findings and the presence of the crystals does not rule out the possibility, but accounts of immunoreactivity for the myogenic regulatory protein MyoD1 have not been confirmed in subsequent studies or in the authors' own staining of six cases.
Ultrastructural studies of tubules, analogous to skeletal cell T-tubules, in alveolar soft part sarcoma.
Nakano H, Park P, Ohno T.
Department of Orthopaedic Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
J Orthop Sci 1998;3(3):143-9 Abstract quote
Tumor tissues from six patients with alveolar soft part sarcoma (ASPS) were investigated ultrastructurally to determine the presence of smooth tubules associated with plasmalemmal invaginations.
Two different types of smooth tubular structures were identified: an aggregated and a dispersed type. The aggregated type (found in one of the six ASPSs) showed marked aggregation of many elongated smooth tubules without ribosomes associated with the plasmalemma. In the dispersed type (observed in the remaining five ASPSs), there was a conspicious appearance of a few smooth tubules scattered throughout the cytoplasm. Smooth tubules were the main component in both types, suggesting that both types appeared to have the same origin, although there were some differences in number, appearance, and distribution of the tubules between the two types. The smooth tubules in both types were classified into three different subtypes on the basis of materials in the tubular lumen.
Ultrastructual observation and a plasmalemmal tracer-method, showed smooth tubules in continuity with the plasmalemma in three of the six cases, indicating that the tubules originated from the plasmalemma. Since the tubular structures were found in the tumor tissues of all six patients, they are probably one of the characteristic features of ASPS.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES Primary renal neoplasms with the ASPL-TFE3 gene fusion of alveolar soft part sarcoma: a distinctive tumor entity previously included among renal cell carcinomas of children and adolescents.
Argani P, Antonescu CR, Illei PB, Lui MY, Timmons CF, Newbury R, Reuter VE, Garvin AJ, Perez-Atayde AR, Fletcher JA, Beckwith JB, Bridge JA, Ladanyi M.
Department of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland 21231-2410, USA.
Am J Pathol 2001 Jul;159(1):179-92 Abstract quote
The unbalanced translocation, der(17)t(X;17)(p11.2;q25), is characteristic of alveolar soft part sarcoma (ASPS). We have recently shown that this translocation fuses the TFE3 transcription factor gene at Xp11.2 to ASPL, a novel gene at 17q25.
We describe herein eight morphologically distinctive renal tumors occurring in young people that bear the identical ASPL-TFE3 fusion transcript as ASPS, with the distinction that the t(X;17) translocation is cytogenetically balanced in these renal tumors. A relationship between these renal tumors and ASPS was initially suggested by the cytogenetic finding of a balanced t(X;17)(p11.2;q25) in two of the cases, and the ASPL-TFE3 fusion transcripts were then confirmed by reverse transcriptase-polymerase chain reaction. The morphology of these eight ASPL-TFE3 fusion-positive renal tumors, although overlapping in some aspects that of classic ASPS, more closely resembles renal cell carcinoma (RCC), which was the a priori diagnosis in all cases. These tumors demonstrate nested and pseudopapillary patterns of growth, psammomatous calcifications, and epithelioid cells with abundant clear cytoplasm and well-defined cell borders.
By immunohistochemistry, four tumors were negative for all epithelial markers tested, whereas four were focally positive for cytokeratin and two were reactive for epithelial membrane antigen (EMA) (one diffusely, one focally). Electron microscopy of six tumors demonstrated a combination of ASPS-like features (dense granules in four cases, rhomboid crystals in two cases) and epithelial features (cell junctions in six cases, microvilli and true glandular lumens in three cases). Overall, although seven of eight tumors demonstrated at least focal epithelial features by electron microscopy or immunohistochemistry, the degree and extent of epithelial differentiation was notably less than expected for typical RCC. We confirmed the balanced nature of the t(X;17) translocation by fluorescence in situ hybridization in all seven renal tumors thus analyzed, which contrasts sharply with the unbalanced nature of the translocation in ASPS.
In summary, a subset of tumors previously considered to be RCC in young people are in fact genetically related to ASPS, although their distinctive morphological and genetic features justify their classification as a distinctive neoplastic entity. Finally, the finding of distinctive tumors being associated with balanced and unbalanced forms of the same translocation is to our knowledge, unprecedented.
PROGNOSIS AND TREATMENT CHARACTERIZATION Alveolar soft-part sarcoma. A clinico-pathologic study of half a century.
Lieberman PH, Brennan MF, Kimmel M, Erlandson RA, Garin-Chesa P, Flehinger BY.
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York.
Cancer 1989 Jan 1;63(1):1-13 Abstract quote
In the period from 1923 to 1986 our pathologists examined pathologic material from 102 patients with alveolar soft-part sarcoma (ASPS). Followup clinical data is available for 91. Median followup is 7 years (range 1 month to 27 years). Local recurrence was only found if residual disease was left at the time of the original excision.
Survival in those patients who presented without metastases was 77% at 2 years, 60% at 5 years, 38% at 10 years and 15% at 20 years (median 6 years). No survival advantage could be demonstrated for patients who received chemo and/or radiotherapy, although numbers are small and staging not uniform. An evaluation by electron microscopy and immunohistochemistry cannot confirm recent claims that ASPS is a muscle tumor.
ASPS is an unusual neoplasm; the primary therapeutic option is aggressive surgical excision. Survival even with the development of metastases can be long.
Alveolar soft-part sarcoma. A report of ten cases.
Nakashima Y, Kotoura Y, Kasakura K, Yamamuro T, Amitani R, Ohdera K.
Section of Surgical Pathology, Kyoto University Hospital, Japan.
Clin Orthop 1993 Sep;(294):259-66 Abstract quote
The clinical and pathologic features of ten cases of alveolar soft-part sarcoma (ASPS) were observed in subjects aged ten to 49 years.
Eight were male and two were female. The lesion involved the thigh in six cases and the adjacent bone in three. All lesions were retrospectively classified as high risk (Stage II or III of Enneking's staging system), and distant metastasis to lung or bone was noted at initial presentation in four patients. Three patients died with distant metastases at a mean time of three years seven months after diagnosis. T
he mean interval from initial presentation to detection of distant metastasis was nine months; and the mean interval from detection of metastasis to death was three years two months.
Ultrastructural studies demonstrated typical organoid arrangement of the neoplastic cells surrounded by a basement membrane with close attachment of individual cells to the basal lamina.
No local recurrence, even in cases with inadequate tumor control, and the tendency for distant metastasis demonstrated in the current series, reemphasized that management of metastasis is most important in the treatment of ASPS.
Alveolar soft part sarcoma in children and adolescents: clinical features and outcome of 11 patients.
Pappo AS, Parham DM, Cain A, Luo X, Bowman LC, Furman WL, Rao BN, Pratt CB.
Department of Hematology/Oncology, St Jude Children's Research Hospital, Memphis, TN 38105-2794, USA.
Med Pediatr Oncol 1996 Feb;26(2):81-4 Abstract quote
The clinical features and response to therapy of pediatric alveolar soft part sarcoma, a rare soft tissue sarcoma of uncertain histogenesis, have not been previously described in detail in the literature.
We retrospectively reviewed the clinical characteristics of all patients with alveolar soft part sarcoma who were seen at our institution over a 32-year period.
We found 11 patients with the diagnosis of alveolar soft part sarcoma. Their ages ranged from 2.8-16 years (median 9.8). Staging was determined using the Intergroup Rhabdomyosarcoma Study clinical grouping system and the UICC TNM system. Accordingly, there were six patients with grossly resected tumors (clinical groups I and II) and five with unresected or metastatic disease (clinical groups III and IV).
Children with resected disease were more likely to have smaller noninvasive tumors. The main feature predictive of survival was tumor resectability, since chemotherapy in various combinations failed to produce significant tumor responses. Nine patients are disease-free with a median follow-up of 11.9 years. Surgical resection remains the mainstay of therapy for pediatric alveolar soft part sarcoma. Since active chemotherapy agents have not been identified, patients with unresected or metastatic disease may benefit from experimental agents. The survival rate of this cohort is superior to that seen in adults.
Alveolar soft part sarcoma in children and adolescents: A report from the Soft-Tissue Sarcoma Italian Cooperative Group.
Casanova M, Ferrari A, Bisogno G, Cecchetto G, Basso E, De Bernardi B, Indolfi P, Fossati Bellani F, Carli M.
Pediatric Oncology Unit, Istituto Nazionale Tumori, Milan, Italy.
Ann Oncol 2000 Nov;11(11):1445-9 Abstract quote
BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare malignant tumor and little is known about its clinical features and management. We report on a series of 19 pediatric patients managed over 20 years.
PATIENTS AND METHODS: Primary conservative surgery was performed in all patients and was radical in nine, non-radical in three; seven patients underwent biopsy alone (3 unresectable tumors, 4 metastatic disease). In two cases radical surgery was performed after primary chemotherapy. Radiotherapy was delivered to 8 patients, chemotherapy to 15.
RESULTS: After a median follow-up of 74 months, the five-year survival was 80% for the whole series, 91% for patients with localized disease, 100% for patients with tumor < or = 5 cm, and 31% for those > 5 cm; 16 of 19 patients were alive (12 of 12 with grossly-resected tumor in first continuous remission). Chemotherapy achieved two partial remission among seven evaluable patients.
CONCLUSIONS: Pediatric ASPS has a more favorable prognosis than its adult counterpart. In this series, tumor size correlates with metastatic disease at onset and is the major factor influencing survival. Surgery is the mainstay of therapy. The effectiveness of adjuvant therapy remains to be established, though radiotherapy may be advisable in cases of inadequate surgery.
METASTASES
Colic metastases of alveolar soft-part sarcoma: A case report and review of the literature.
Zilber S, Brouland JP, Voisin MC, Ziza JM, Desplaces N, Chekulaev D, Hobeika J, Houdart R.
Ann Diagn Pathol. 2003 Oct;7(5):306-9. Abstract quote
Alveolar soft-part sarcoma is a rare soft tissue malignant tumor that commonly arises in skeletal muscles or musculofascial planes in children and young adults. Metastases of lung, brain, and bone are often present at the time of diagnosis or appear late in the course of disease.We present the first case, to our knowledge, of colic metastases in a 43-year-old woman who had a leg primary tumor more than 15 years ago and multiple lung and brain metastases. The treatment of these two caecal metastases, revealed by an anemia, consisted in laparoscopic right colectomy.
Alveolar soft part sarcoma: an unusually long interval between presentation and brain metastasis.
Lillehei KO, Kleinschmidt-DeMasters B, Mitchell DH, Spector E, Kruse CA.
Department of Surgery, University of Colorado Health Sciences Center, Denver 80262.
Hum Pathol 1993 Sep;24(9):1030-4 Abstract quote
While alveolar soft part sarcoma is an uncommon soft tissue tumor known for late metastases to lung, bone, and brain, and interval of 33 years between primary presentation and development of brain metastasis has not been described.
We document a patient with a removal of an alveolar soft part sarcoma from the pectoralis major muscle at the age of 10 years, a lung metastasis at the age of 31 years, and brain and renal masses at the age of 43 years. The patient received surgical resections each time, but never radiotherapy or chemotherapy. He is currently alive and well. Immunohistochemistry, karyotypic analysis, flow cytometry, and gene expression were analyzed on primary tumor and established cell cultures in the hopes of further elucidating the histogenesis of this unusual neoplasm.
Metastatic alveolar soft part sarcoma presenting as a dural-based cerebral mass.
Perry JR, Bilbao JM.
Division of Neurology, St. Michael's Hospital, Toronto, Ontario, Canada.
Neurosurgery 1994 Jan;34(1):168-70 Abstract quote
Sarcoma metastatic to the brain is uncommon and rarely occurs as the initial manifestation of tumor. Alveolar soft-part sarcoma, a rare but well studied subtype of a soft tissue sarcoma with a propensity for central nervous system invasion, presenting with brain metastases, has been reported only once previously.
We report the case of a 28-year-old man who presented with partial seizures and who was found to have a homogeneously enhancing frontal lesion on a broad dural base disclosed by computed tomography. preoperatively, the lesion was thought to be a meningioma. The tumor was excised easily and had features typical of an alveolar soft-part sarcoma, which were revealed by light and electron microscopy as well as immunohistochemical analysis. Multiple lung nodules compatible with metastases were found on a chest film. Meningeal dissemination has been reported in a variety of sarcoma types, including rhabdomyosarcoma, fibrosarcoma, and leiomyosarcoma.
We add alveolar soft-part sarcoma to this list and suggest that increased recognition of the propensity for these tumors to exhibit metastatic spread to the dura should eliminate diagnostic confusion and provide an earlier diagnosis of these rare lesions. The patterns of spread in metastatic sarcoma deserve further study.
Alveolar soft part sarcoma metastatic to the breast.
Hanna NN, O'Donnell K, Wolfe GR.
Department of Surgery, St. Elizabeth's Medical Center of Boston, Tufts University School of Medicine, Massachusetts 02135, USA.
J Surg Oncol 1996 Feb;61(2):159-62 Abstract quote
Metastasis to the breast is uncommon, with an incidence of 0.5-3%. Alveolar soft part sarcoma is rare, accounting for < 1% of malignant soft tissue tumors, which are themselves unusual. Excluding contralateral breast and hematologic malignant disease, the primary lesion in most cases of metastasis to the breast is melanoma, small cell carcinoma of the lung, or ovarian carcinoma, although rhabdomyosarcoma is the most common primary tumor in children.
We describe a 26-year-old woman with no history of malignant disease who presented with two masses in the right breast that clinical evaluations and ultrasonography indicated were fibroadenomas. Pathological studies after excisional biopsy, however, indicated alveolar soft part sarcoma. Subsequent computed tomography showed the primary tumor in the anterior left thigh and multiple bilateral lung metastases.
Because of the presence of distant metastases, the patient was treated with chemotherapy.
Alveolar soft part sarcoma: clinical course and patterns of metastasis in 70 patients treated at a single institution.
Portera CA Jr, Ho V, Patel SR, Hunt KK, Feig BW, Respondek PM, Yasko AW, Benjamin RS, Pollock RE, Pisters PW.
The University of Texas M. D. Anderson Cancer Center Multidisciplinary Sarcoma Center, Houston 77030-4009, USA.
Cancer 2001 Feb 1;91(3):585-91 Abstract quote
BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare form of soft tissue sarcoma. Brain metastases have been reported to be a common feature of Stage IV ASPS, and recent practice guidelines recommend routine intracranial imaging as part of the staging evaluation in all patients who present with ASPS.
METHODS: The authors performed a comprehensive retrospective review of the clinical presentation, treatment, outcome, and patterns of failure in a consecutive series of patients with localized (American Joint Committee on Cancer [AJCC] Stages II/III) or metastatic (AJCC Stage IV) ASPS who presented to a tertiary care cancer center between 1959 and 1998.
RESULTS: Seventy-four patients were identified from the database searches. The anatomic distribution of their primary tumors included: extremities, 44 patients (60%); trunk, 15 patients (20%); head and neck, 9 patients (12%); and retroperitoneum, 6 patients (8%). The median tumor size was 6.5 cm (range, 1.2-24 cm). The AJCC stage at presentation was Stage II or III in 35% of the patients and Stage IV in 65% of the patients. The 5-year actuarial local recurrence free, distant recurrence free, disease free, and overall survival rates among the 22 patients with localized ASPS were 88%, 84%, 71%%, and 87%, respectively. At a median follow-up of 9 years, 2 of 22 patients with localized disease had developed local recurrences and 3 had developed metastatic disease (all to the lung only). Brain metastases were noted in 9 of 48 patients who presented with Stage IV (M1) disease (19%) and always were noted in association with metastasis to other sites. The median survival of patients with M1 disease was 40 months, with a 5-year survival rate of 20%.
CONCLUSIONS: Long term follow-up of patients with localized ASPS reveals a relatively indolent clinical course with relatively low rates of local and distant recurrence. In patients with Stage IV ASPS, brain metastases were observed only as part of more disseminated disease. The observations of the current study do not support current practice guidelines for the staging of patients with ASPS and suggest that selective rather than routine intracranial imaging should be used in patients presenting with ASPS.
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