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Background
This is a rare soft tissue sarcoma which predominately occurs on acral sites. These tumors vary in size from a few centimeters to almost 20 centimeters. They typically occur on hands and feet, usually around the ankles or wrists. They are slow growing and painless. Treatment usually is complete excision. There are reports of local recurrence as well as metastasis to the lymph nodes and lungs.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS Acral Myxoinflammatory fibroblastic sarcoma
Inflammatory myxohyaline tumor of distal extremities
Inflammatory myxoid tumor of soft parts with bizarre cellsINCIDENCE Rare AGE RANGE-MEDIAN Adults, wide age range About equal
PATHOGENESIS CHARACTERIZATION CHROMOSOMAL ABNORMALITIES
Acral myxoinflammatory fibroblastic sarcoma with unique clonal chromosomal changes.Lambert I, Debiec-Rychter M, Guelinckx P, Hagemeijer A, Sciot R.
Department of Pathology, University of Leuven, University Hospital St. Rafael, Belgium.
Virchows Arch 2001 May;438(5):509-12 Abstract quote Acral myxoinflammatory fibroblastic sarcoma is a rare tumor of the distal extremities. We present the hitherto unreported karyotypic abnormalities of this new entity. The tumor presented as a mass in the dorsum of the foot in a 53-year-old woman and showed the typical virocyte-like and lipoblast-like cells in a myxoid and inflammatory background.
Cytogenetic analysis revealed a complex karyotype with a reciprocal translocation t(1;10) (p22;q24) in addition to the loss of chromosomes 3 and 13. Fluorescence in situ hybridization with the 769E11YAC and BAC 31L5 and 2H23 probes showed the breakpoint to be located proximally to BCL10 and distally to GOT1 genes on chromosomes 1p22 and 10q24, respectively.
The presence of these clonal chromosomal changes supports the neoplastic nature of acral myxoinflammatory fibroblastic sarcoma and underscores that it represents a separate entity.
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION GENERAL Acral myxoinflammatory fibroblastic sarcoma: case series and immunohistochemical analysis
Kovarik CL, Barrett T, Auerbach A, Cassarino DS.
J Cutan Pathol 2008; 35: 192–196 Abstract quoteBackground: Acral myxoinflammatory fibroblastic sarcoma (AMFS) is a rare, low-grade neoplasm most often occurring on the extremities of adults. It consists of mixed inflammatory infiltrates with nodules of epithelioid, spindled and bizarre-appearing cells within a fibrosclerotic-to-myxoid stroma. AMFS frequently recurs, but only rarely metastasizes.
Materials and methods: A retrospective analysis of all cases of AMFS seen in the past 4 years from the Stanford University Laboratory of Surgical Pathology and collaborating institutions was performed. We sought to better characterize the clinicopathologic characteristics of this rare tumor. Immunohistochemical stains, including CD34, epithelial membrane antigen (EMA), epidermal growth factor receptor (EGFR), CD117, CD163, Ki67 and p53, were also performed.
Results: Eighteen cases were analyzed, and clinical information was available on 13 of them. The mean age at diagnosis was 48 years old, 10/13 (77%) occurred on the distal extremities and diameter of the lesions ranged from 1.0 to 10.0 cm. Treatment included wide local or radical excision and local recurrences were not reported. Many of the lesions were multinodular. Histologic characteristics included the presence of fibrosclerotic and myxoid stroma, sheets of spindled to round epithelioid cells, Reed-Sternberg or virocyte-like cells, lipoblast-like cells and rare mitotic figures. In most cases, CD34, EGFR and CD163 were diffusely positive. EMA and CD117 were weakly positive in some cases. Ki67 labeled < 10% of cells, and staining with P53 was variable.
Conclusions: Because AMFS may be mistaken for lymphoma, infection or tumors with higher metastatic potential, correct diagnosis is important to avoid unnecessary procedures and allow for proper clinical management. EGFR positivity suggests possible therapeutic use in aggressive cases.
- Acral myxoinflammatory fibroblastic sarcoma: a report of five cases and review of the literature.
Sakaki M, Hirokawa M, Wakatsuki S, Sano T, Endo K, Fujii Y, Ikeda T, Kawaguchi S, Hirose T, Hasegawa T.
Department of Pathology, University of Tokushima School of Medicine, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
Virchows Arch. 2003 Jan;442(1):25-30. Epub 2002 Nov 5. Abstract quote
Five cases of acral myxoinflammatory fibroblastic sarcoma that occurred in the distal extremities within the subcutaneous tissue are described. In one case, recurrence and metastases were recognized rather rapidly, only 3 months after the first excision. There have been no reports of early recurrence or metastases, especially the latter. The predominant type of constituent cells, cellularity of the neoplastic cells and density of inflammatory cells varied microscopically among cases. However, characteristic ganglion-like cells, Reed-Sternberg-like cells, round mononuclear cells and myxoid stroma, sometimes only seen focally, were found in all cases.
Positive immunoreaction for vimentin was present in all cases. There was no correlation between positivity of MIB-1 or p53 for the primary tumor and presence of recurrence or metastases.
In conclusion, we should be more cautious about the possibility of recurrence or metastases in earlier phases of acral myxoinflammatory fibroblastic sarcoma. Identification of the atypical bizarre fibroblastic component as the manifestation of the malignant nature of this lesion is vital to correct diagnosis, and it is important to attend to the myxoid and hyalinized zones, the inflammatory infiltrate, the presence of ganglion-like cells and acral location as features of acral myxoinflammatory fibroblastic sarcoma.VARIANTS NON-ACRAL TUMORS
Department of Plastic and Reconstructive Surgery, Chaim Sheba Medical Center, Tel Hashomer, Affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Background: Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare tumor presenting as a painless subcutaneous mass in the extremities first reported in 1998. We report the first case of a MIFS tumor in the groin.
Methods: We have performed seven immunohistochemical stains that were not applied before on MIFS.
Results: The first case of a MIFS tumor in the groin.
Conclusions: MIFS must be considered in the differential diagnosis of a painless mass not only in the distal extremities but also in the groin. The diagnosis of this tumor is difficult and can be missed if not considered because of the unusual location. Due to high recurrence rates and one case of documented metastases, the recommended treatment is wide excision.
- Myxoinflammatory fibroblastic sarcoma of the neck.
McFarlane R, Meyers AD, Golitz L.
Departments of Dermatology and Pathology, University of Colorado School of Medicine, Denver, CO, USA.
J Cutan Pathol. 2005 May;32(5):375-8. Abstract quote
Background: Myxoinflammatory fibroblastic sarcoma (MIFS), also named inflammatory myxohyaline tumor of distal extremities with virocyte or Reed-Sternberg cells, is a rare tumor typically presenting as a painless mass in the extremities.
Patients: We present an unusual case of MIFS presenting as a subcutaneous neck mass. This is the first reported case of MIFS presenting in the neck.
Results: Therefore, this lesion must be considered in the differential diagnosis for painless subcutaneous masses presenting not only in the distal extremities, but also in the neck.
Conclusion: MIFS has only recently been recognized. The differential diagnosis for MIFS is broad, and it can often be mistaken for several different inflammatory and neoplastic processes, which may require different treatment.
Myxoinflammatory fibroblastic sarcoma: a tumor not restricted to acral sites.Jurcic V, Zidar A, Perez Montiel MD, Frkovic-Grazio S, Nayler SJ, Cooper K, Suster S, Lamovec J.
Department of Pathology, University of Ljubljana, Slovenia
Ann Diagn Pathol 2002 Oct;6(5):272-80 Abstract quote We report on nine new cases of myxoinflammatory fibroblastic sarcoma; in six of them the location of the tumor was distal (acral), and proximal in three (forearm, arm, and thigh). Tumors varied in size from 1.5 to 18 cm, were well-circumscribed, yellow-tan, and focally myxomatous.
Histologically, they were similar in appearance and showed vaguely lobular architecture and oval, spindle, and epithelioid neoplastic cells with scattered, focally aggregated inflammatory cells. In all cases, in different numbers, bizarre giant cells with large, lobulated, or multiple nuclei were also admixed, some of them morphologically imitating Reed-Sternberg cells, lipoblasts, or ganglion cells; they showed distinct nucleoli or intranuclear inclusions. Myxoid areas were always present, to different extent. Immunohistochemically, tumor cells were uniformly positive for vimentin; some cells were also positive for CD68 and CD34. Ultrastructurally, tumor cells were nondescript, consistent with fibroblastic origin.
On flow cytometry, two of the examined cases showed diploid pattern with low S-phase fraction. In none of the cases, metastases were observed, in one case the tumor recurred 5 years following surgery.
We conclude that myxoinflammatory fibroblastic sarcoma is a distinct soft tissue tumor of low-grade malignancy and, until now, described only in extremities, although not confined to acral sites.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL
Inflammatory myxoid tumor of the soft parts with bizarre giant cells.Michal M.
Medical Faculty, Charles University Pilsen, Czech Republic.
Pathol Res Pract 1998;194(8):529-33 Abstract quote We present five cases of a tumor which we named inflammatory myxoid tumor of the soft parts with bizarre giant cells and which is often misdiagnosed as a malignant neoplasm.
The tumors were located in the soft tissues of the fingers and hand and were 1 to 2.5 cm in the largest diameter (median 2 cm). The tumors were divided by fibrous septa into lobules. The lobules were composed of numerous proliferating capillaries and tumor cells, both set in copious myxoid extracellular matrix. Variously dense inflammatory infiltrate represented by numerous lymphocytes and plasma cells and sparse neutrophil leukocytes surrounded the capillaries. The tumor cells had one, two, or more nuclei. The nuclei of the tumor cells were vesicular, often indented or cleaved and they usually had one small nucleolus. The cytoplasm displayed characteristic clear vacuoles filled with mucous substances. In some of the tumor cells the cytoplasmic vacuoles filled the whole cytoplasm and compressed or indented the nucleus. Such cells had an appearance of signet ring cells. The cytoplasm of some of the cells often contained lymphocytes and leukocytes.
All four patients with follow-up were without signs of recurrence and metastasis 2, 4, 6 and 7 years after the diagnosis.
Inflammatory myxohyaline tumor of distal extremities with virocyte or Reed-Sternberg-like cells: a distinctive lesion with features simulating inflammatory conditions, Hodgkin's disease, and various sarcomas.Montgomery EA, Devaney KO, Giordano TJ, Weiss SW.
Department of Pathology, Georgetown University, Washington, DC, USA.
Mod Pathol 1998 Apr;11(4):384-91 Abstract quote We report 51 cases of a previously undescribed tumor of the distal extremities that is often mistaken for an inflammatory or infectious process, Hodgkin's disease, or various sarcomas.
These lesions developed in patients of all ages (range, 4-81 yr; median, 40 yr) and affected the sexes nearly equally (27 men, 24 women). They presented as a painless mass of the fingers (14 cases), hand (11 cases), wrist or arm (10 cases), toe or foot (8 cases), or lower leg (5 cases), usually within the subcutaneous tissues. Grossly, they were infiltrative, multinodular masses characterized by a dense chronic inflammatory infiltrate that merged with a stroma, which varied from densely hyaline to focally myxoid and contained sheets of short spindled to rounded epithelioid cells. Focally, the epithelioid cells were extremely large with bizarre, vesicular nuclei and macronucleoli resembling Reed-Sternberg cells or virocytes. Despite the level of atypia, mitotic activity was low.
The tumor cells consistently expressed vimentin but lacked a variety of other mesenchymal, epithelial markers, e.g., S100 protein, desmin, actin, neuron-specific endolase, epithelial membrane antigen, HMB-45, CD34) and leukocyte markers (CD15, CD30, CD45). Keratin was noted focally and weakly in four cases and CD68 focally in six cases, the latter suggesting that the cells had acquired phagocytic properties. Immunostains for cytomegalovirus were negative. Polymerase chain reaction for Epstein-Barr virus showed amplification levels consistent with latent infection in 4 of 10 cases, but no cases showed levels consistent with active infection. All of the bacterial and viral cultures were negative. Follow-up information was available in 27 cases. Recurrences developed in six patients (interval, 15 mo-10 yr), but there were no metastases or tumor-related deaths. In one patient, progressive proximal extension up the arm was noted.
Although the most common submitting diagnosis was that of an inflammatory or infectious process, the negative studies for infectious agents, clinical behavior with local recurrences, immunophenotypic profile, and cytologic atypia support the idea that these are unusual mesenchymal neoplasms with at least the potential for local recurrence. It remains to be investigated whether with time these lesions will prove to have metastatic potential.
Acral myxoinflammatory fibroblastic sarcoma: a low-grade tumor of the hands and feet.Meis-Kindblom JM, Kindblom LG.
Department of Pathology, Gothenburg Musculoskeletal Tumor Center, Sahlgrenska University Hospital, University of Gothenburg, Sweden.
Am J Surg Pathol 1998 Aug;22(8):911-24 Abstract quote Acral myxoinflammatory fibroblastic sarcoma is a unique low-grade tumor of modified fibroblasts. It characteristically occurs in the distal extremities and has a propensity to recur locally.
Forty-four cases that occurred in 22 males and 22 females from 20 to 91 years of age (median, 53 years) were studied. The lesions, which were 1-6 cm (median, 3 cm), occurred in the hands (64%), the feet (20%), the ankles (11%), and the wrists (5%). The patients usually had a long history of a painless mass (median duration, 1 year).
Clinically they were suspected to be ganglion cysts, tenosyonovitis, or giant cell tumors of tendon sheath. Initial histologic diagnoses, in most cases, included pigmented villonodular tenosynovitis or various reactive fibroinflammatory processes. Histologically, the lesions were multinodular, poorly delineated, and characterized by a prominent myxoid matrix containing numerous inflammatory cells, including polymorphonuclear leukocytes, eosinophils, lymphocytes, and plasma cells, as well as fibrosis. Amidst the prominent inflammation, and sometimes obscured by it, were scattered, large, bizarre tumor cells with vesicular nuclei, prominent inclusion-like nucleoli, and abundant eosinophilic cytoplasm, which was homogeneous to vacuolated and often contained intracytoplasmic inflammatory cells.
Ultrastructurally, the bizarre tumor cells had features of modified fibroblasts, including an abundance of intermediate filaments and dilated rough endoplasmic reticulum.
Immunohistochemically, the neoplastic cells revealed strong positivity for vimentin (25 of 25), focal positivity for CD68 antigen (17 of 25) and CD34 (7 of 25); the tumor cells did not express neuroectodermal, epithelial, or lymphoid markers. The Ki67 labeling index with MIB1 was less than 1% in 20 of 25 cases; p53 immunoreactivity (20-90%) was observed in 7 of 25 primary tumors and in 2 of 3 local recurrences.
Follow-up information was available in 36 of 44 cases (median, 5 years). Most excisions were either intralesional or marginal. Ten patients underwent amputation, usually after repeated local recurrences. Radiation therapy and chemotherapy were administered in five and two cases, respectively. Twenty-four cases (67%) had at least one local recurrence. A histologically proven lymph node metastasis developed in one patient, whereas another was stated to have lung metastases, although these were not documented histologically.
At last follow-up, 23 patients were alive and well, 11 were alive with disease, and 2 were dead of other causes without evidence of tumor. The prominent inflammation and fibrosis seen histologically in acral myxoinflammatory fibroblastic sarcoma simulate a reactive process. The presence of myxoid foci and scattered bizarre cells, which are occasionally multivacuolated, may cause confusion with malignant fibrous histiocytoma and liposarcoma.
Based on the protracted clinical course, a high rate of local recurrence (sometimes necessitating amputation), and a low rate of metastasis, we believe these tumors are low-grade sarcomas. The intimate relationship with the synovium, the frequent association with tenosynovitis, and the prominent inflammatory infiltrate suggest that inflammation may play a role in the pathogenesis of acral myxoinflammatory fibroblastic sarcoma.
SPECIAL STAINS/
IMMUNOPEROXIDASE/
OTHERCHARACTERIZATION SPECIAL STAINS IMMUNOPEROXIDASE Positivity for vimentin
Focal positivity for CD68 antigen and CD34Negative for neuroectodermal, epithelial, or lymphoid markers
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES LOW GRADE FIBROMYXOID SARCOMA
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSTIC FACTORS Low grade sarcoma with potential for local recurrence and metastasis Acral myxoinflammatory fibroblastic sarcomas: are they all low-grade neoplasms?
Hassanein AM, Atkinson SP, Al-Quran SZ, Jain SM, Reith JD.
J Cutan Pathol 2008; 35: 186–191. Abstract quote
Acral myxoinflammatory fibroblastic sarcoma (AMIFS) is a low-grade sarcoma that presents mostly in distal extremities of middle-aged patients. The clinicopathologic features, immunohistochemical profile and follow-up data of five cases (three men and two women; age 39–65 years) are presented.
The tumors presented as a slow-growing, poorly circumscribed, subcutaneous masses in the hands (three), foot (one) and calf (one), with dermal involvement in two cases. They had myxoid and hyaline stroma with dense acute and chronic inflammation. Spindle cells, large bizarre ganglion-like cells and multivacuolated cells were seen.
Variable reactivity in lesional cells were noted for vimentin, Alpha-1-antitrypsin (A1AT), factor XIIIa, CD68, CD95, CD117, Alpha-1-antichymotrypsin (A1ACT), CD34, AE1/3, S-100 protein, EBER, CD63 and CD15. MIB-1 showed 5–30% nuclear labeling. They were negative for cytokeratin AE1/3, smooth muscle actin, CD30, ALK-1, EMA, desmin, CMV, HMB-45 and Melan-A. Follow up ranged from 2 weeks to 95 months (mean 54). One patient was lost to follow up; three underwent excision and one patient had below the knee amputation. Two patients developed metastases (one died of disease), and two patients are alive without evidence of disease.
AMIFS are rare tumors that may involve joints and tendons leading to clinical diagnosis of ganglion cyst or tenosynovitis.TREATMENT Wide excision Macpherson and Pincus. Clinical Diagnosis and Management by Laboratory Methods. Twentyfirst Edition. WB Saunders. 2006.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fifth Edition. Mosby Elesevier 2008
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