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Year : 2022  |  Volume : 65  |  Issue : 4  |  Page : 921-924
Angiomatoid fibrous histiocytoma: Report of two cases, initially construed as sarcoma with unusual clinico-pathological features

1 Department of Pathology, Rajiv Gandhi Cancer Institute and Research Centre, Sector 5, Rohini, Delhi, India
2 Department of Orthopaedic Oncology, Rajiv Gandhi Cancer Institute and Research Centre, Sector 5, Rohini, Delhi, India
3 Department of Radiodiagnosis, Rajiv Gandhi Cancer Institute and Research Centre, Sector 5, Rohini, Delhi, India
4 Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, Sector 5, Rohini, Delhi, India

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Date of Submission27-Dec-2020
Date of Decision01-Jan-2022
Date of Acceptance07-Jan-2022
Date of Web Publication08-Jun-2022


Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor of uncertain differentiation with low metastatic potential, most commonly occurring in children, adolescents, and young adults, involving extremities. Due to its rare nature and diverse presentation, both clinically and morphologically, it is often misdiagnosed. It becomes important to correctly diagnose this lesion, given its distinct therapeutic implications. Here, we present the clinical, radiologic, and pathologic findings of two rare cases of AFH. Since AFH is a rare soft tissue tumor with low malignant potential, both pathologists and clinicians should be aware of this entity, when encountered with a soft tissue mass in extremities of a child or adolescent, so as to accord appropriate treatment in such cases.

Keywords: Angiomatoid fibrous histiocytoma, EWSR1-ATF1, EWSR1-CREB1

How to cite this article:
Pasricha S, Durga G, Sharma A, Pruthi M, Kamboj M, Gupta G, Jajodia A, Mahawar V, Babu Koyyala VP, Mehta A. Angiomatoid fibrous histiocytoma: Report of two cases, initially construed as sarcoma with unusual clinico-pathological features. Indian J Pathol Microbiol 2022;65:921-4

How to cite this URL:
Pasricha S, Durga G, Sharma A, Pruthi M, Kamboj M, Gupta G, Jajodia A, Mahawar V, Babu Koyyala VP, Mehta A. Angiomatoid fibrous histiocytoma: Report of two cases, initially construed as sarcoma with unusual clinico-pathological features. Indian J Pathol Microbiol [serial online] 2022 [cited 2022 Nov 30];65:921-4. Available from:

   Introduction Top

Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor of uncertain differentiation with low metastatic potential. These slow growing tumors typically involve the superficial mucocutaneous tissues of the extremities in children and young adults and rarely outside the somatic soft tissue, hence broadening the anatomical soft tissue location which can be involved by this tumor.

Grossly, it is a firm, circumscribed gray-tan to red-brown neoplasm displaying characteristic irregular blood-filled cystic spaces filled with hemorrhage on cut section, thus giving the impression of a vascular tumor/thrombosed vessel. Microscopically, there are sheets of uniform bland histiocyte-like cells with intervening cystic spaces filled with hemorrhage surrounded by a peripheral cuff of inflammatory cells and a pseudo capsule. These spaces are lined by flattened tumor cells and not endothelium. Rarely, these tumors may show myxoid change/small cell pattern/alveolar pattern/spindle cell pattern, and thus may mimic other soft tissue tumors very easily. On the immunohistochemistry (IHC) front, positive co-expression of desmin, Epithelial Membrane Antigen (EMA) and CD68, along with negative expression of other muscle markers, is highly characteristic feature of AFH.

This tumor has a diverse presentation of histological and clinical presentation and is often misdiagnosed as other soft tissue tumors. Its accurate diagnosis encompasses thorough exclusions of various differential diagnosis based on the clinical, histomorphological and IHC profile.[1],[2],[3]

Given its distinct therapeutic implications and to circumvent overtreatment with toxic chemotherapy, a precise diagnosis is of paramount importance. We report two unusual cases of AFH, one with deceptive small round cell tumor morphology mimicking Ewings sarcoma and the second case, located in the deep intramuscular compartment masquerading as sarcoma on clinico-radiological workup.

   Case Report Top

Case 1

A six-years-old female child presented with complaints of pain and swelling in the right lower limb just below the knee on the posteromedial aspect without any difficulty in joint movement. She was referred to our institute as a diagnosed case of Ewing's sarcoma. On local examination, the swelling was firm, tender, partially mobile, and measured 6 × 5 × 4 cm. Ultrasonography revealed an oval cystic mass which was relatively circumscribed. Systemic examination and general examination was normal. Routine hematological and biochemical tests were normal. Submitted slides and blocks from wedge biopsy, showed a proliferation of round to oval neoplastic cells in sheets and cords exhibiting mild to moderate nuclear atypia with scant to moderate pale eosinophilic cytoplasm. Mitotic activity was significant (6-8/10 hpf) and no necrosis was evident [Figure 1]a, [Figure ]b. The background stroma was fibrocollagenous. A fragmented thick capsule was noted in some areas with only focal infiltration by lymphoplasmacytic cells. No significant lymphocytic cuffing was noted. Overall histomorphological features were suggestive of malignant mesenchymal tumor – small round cell tumor.
Figure 1: (a) Proliferation of round-oval neoplastic cells in sheets and cords (H&E, x100). (b) cells display moderate nuclear atypia, moderate pale eosinophilic cytoplasm and frequent mitosis. (H&E; x400). (c) EMA immunoreactivity (Diaminobenzidine; ×400). (d) Desmin immunoreactivity (Diaminobenzidine; ×400). (e) TLE1 immunoreactivity (Diaminobenzidine; 400). f: CD99 immunoreactivity (Diaminobenzidine; ×400)

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On IHC, the tumor cells were strongly positive for TLE-1 [Figure 1]e, vimentin, CD99 [Figure 1]f while negative for CK, SMA, S-100, CD31, Caldesmon-H, myogenin, and Myo D1. Above findings ruled out rhabdomyosarcoma and pointed toward the possibility of Ewings sarcoma and synovial sarcoma. However, overall the clinicopathological profile: a well circumscribed mass in superficial compartment, exhibiting low mitosis, provoked us to rule out AFH. Subsequently desmin [Figure 1]c and EMA [Figure 1]d IHC stains were applied which were diffusely and strongly positive. Overall histopathological features espoused with the clinical findings suggested the diagnosis of AFH.

Contrast magnetic resonance image (MRI) revealed an irregular lobulated altered signal intensity mildly enhancing lesions with cystic areas measuring 6 × 2.9 × 1.9 cm in subcutaneous plane showing perifocal fat stranding abutting deep fascia over gastrocnemius muscle.

Patient subsequently underwent wide local excision of the mass. Grossly, it was a partly skin covered mass measuring 6.5 × 3.2 × 2 cm. Cut surface showed a solid-cystic mass with areas of hemorrhage. Histopathological features showed a similar well circumscribed tumor as described earlier in the wedge biopsy. It was located in the subcutaneous plane and did not infiltrate the muscle. Cystic areas demonstrated areas of hemorrhage. The overlying skin and resection margins were free (closest 0.1 cm). Molecular testing could not be performed in this case. The patient is free of recurrence or metastasis after 50 months of follow up.

Case 2

A 54-years-old male presented with a painless swelling in the right forearm since three months. He was initially evaluated elsewhere and was diagnosed as hemangioendothelioma on trucut biopsy and subsequently referred to our institute. On physical examination, the swelling was deep, firm, immobile, and non-tender. General and systemic examinations were unremarkable. Routine biochemical and hematological investigations were normal. Subsequently, MRI was done which showed a 6.8 × 5.4 × 3.7 cm well circumscribed avidly enhancing mass deep to triceps muscle [Figure 2]a. A working clinic-radiological diagnosis of soft tissue sarcoma was suggested and the patient underwent wide local excision. Gross examination showed a well circumscribed, firm, grey brown lesion [Figure 2]b. Microscopic examination revealed a pseudocapsulated lesion showing proliferation of oval to spindle shaped cells arranged in perivascular fashion exhibiting moderate nuclear atypia although mitotic activity was sparse [Figure 3]a, [Figure 3]b. No necrosis was seen. The background stroma was myxohyaline. Chronic inflammatory infiltrate was seen at the periphery. On the basis of histomorphology, a differential diagnosis of vascular tumor, solitary fibrous tumour, myxofibrosarcoma, and synovial sarcoma was made.
Figure 2: (a) Axial T2 weighted MRI image shows a well circumscribed mass deep to triceps muscle (arrow). The adjacent bony cortex is intact. (b) Gross photograph shows solid, well circumscribed, firm, grey brown tumor

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Figure 3: (a) Encapsulated neoplasm composed of round-oval neoplastic cells in sheets. (H&E; x100) (b) cells display mild to moderate nuclear atypia and an occasional mitosis. (H&E, x200) (c) EMA immunoreactivity. Perivascular arrangement of cells is noted. (Diaminobenzidine; ×200) (d) Desmin immunoreactivity (Diaminobenzidine; ×200)

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The primary panel of IHC markers comprised CK, CD31, MUC4, SMA, S100, STAT6, TLE1, and CD68; however, all were negative and hence ruled out all morphological differentials. Subsequently desmin [Figure 3]c was given which was positive. A well circumscribed mass with low mitotic activity, areas of haemorrhage and chronic inflammatory infiltrate along with desmin expression prompted us to rule out AFH and therefore, EMA IHC [Figure 3]d was applied which was positive while Myogenin and MyoD1 were negative. Overall features suggested a final diagnosis of AFH. Subsequently, EWSR1 gene rearrangement by break apart FISH was also performed which was negative. The patient is presently doing well, free of any recurrence/metastasis after 48 months of follow up.

   Discussion Top

AFH is a rare soft tissue tumor of undetermined differentiation and low malignant potential, which initially reported by Enzinger in 1979, who described 41 cases of “an unusual fibrohistiocytic sarcoma” as a variant of malignant fibrous histiocytoma, however subsequent large studies revealed a favorable prognosis of AFH after wide local excision.[2],[4]

The differential diagnosis of AFH is broad and includes the spectrum ranging from benign lesions to malignant entities, especially in small diagnostic biopsies.

AFH on histomorphology can be confused with benign entities like granuloma especially the solid variant of AFH. Besides this, fibrous histiocytoma forms an another important differential diagnosis, however observation of endothelial cells lined vascular channel espoused with IHC expression of vascular markers like CD31, CD34 easily resolve this differential. Follicular dendritic cell sarcoma is another differential diagnosis as their neoplastic cells are epithelioid to spindle with low mitosis but they are characteristically positive for CD21 and CD23. Round cell variant of AFH can be misdiagnosed as Ewings sarcoma especially when CD99 is strong positive as in the presented case 1. Moreover, EWSR1 rearrangement by Break apart FISH can further complicate the matter as AFH is now established as a translocation associated neoplasm with significant number of cases characterized by chromosomal rearrangement involving EWSR1 gene which is evocative of Ewing sarcoma, hence can lead to self-fulfilling prophecy,[2],[5],[6]

As the molecular genetics of AFH became increasingly understood, genetic testing is often utilized to support the diagnosis of this entity. The three common translocations resulting in fusion genes associated with AFH are: FUS/ATF (t (12;16)(q13;p11)), EWSR1/ATF1: t (12;22)(q13;q12), and EWSR1/CREB1: t (2;22)(q33;q12) fusion genes. Of all these the EWSR1-CREB1 is the most commonly described gene fusion in AFH (> 90% of cases), while EWSR1-ATF1 fusion was most commonly found translocation in extrasomatic soft tissue sites.[1],[2],[6]

Tanas et al.[7] reported that 76% of assessed AFH were shown by FISH to harbor EWSR1 rearrangement. Thway et al.[8] showed that both FISH and Reverse transcription-polymerase chain reaction (RT-PCR) are equally reliable for facilitating an AFH diagnosis because one technique can identify the cases that the other method misses.

As per the prevailing literature, the clinical behavior and prognosis of this entity is favorable and cannot be attributed to the histomorphological, immunohistochemical, or genetic profile. The mitotic activity, extreme pleomorphism, inflammatory response, tumor size, patient age, and adjuvant therapy were not correlated with the clinical behavior.[2],[6],[9]

AFH usually presents with subcutaneous lump in children and young adults, however our case 2 presented in the deep intramuscular compartment, in 54-years-old male which was clinically unusual and suggested a sarcoma. Costa et al.[9] reported that 18% of the tumors invaded deep structures and added that an irregular tumor border as well as a head and neck location were associated with local recurrence, and the depth of the tumor was correlated with subsequent local and distant metastasis. Enzinger et al.[4] analyzed 24 cases and reported that 63% and 21% of patients had local recurrence and metastasis, respectively, and that 12% of patients had died of the disease.

Saito et al.[6] has recently reported a series of seven cases, out of which four cases were initially misdiagnosed as other soft tissue tumors which includes myxoid liposarcoma, Ewings sarcoma, myxofibrosarcoma, and synovial sarcoma. In the presented case 1, which was TLE-1 strong positive, hence could have prompted an erroneous diagnosis of synovial sarcoma. Besides synovial sarcoma, TLE-1 has been reported to be expressed positive in other mesenchymal tumors like benign and malignant sheath tumors, solitary fibrous tumors, rhabdomyosarcomas, which can be potential mimickers of AFH and thus it should be used only in the context of a panel of antibodies.[10],[11]

Therefore, a careful distinction from benign tumors is essential to ensure wide local excision and differentiation from high grade sarcoma is imperative to prevent toxic chemotherapy and radical surgery.[5],[6]

To conclude, AFH is a rare soft tissue tumor of uncertain histogenesis with favorable clinical outcome. Diagnostic adroitness comprising histomorphological assessment along with appropriate IHC, genetic studies and clinicoradiological correlation can resolve the differentials and can establish an accurate diagnosis of AFH which has distinct prognostic and therapeutic implications.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Chen G, Folpe AL, Colby TV, Sittampalam K, Patey M, Chen MG, et al. Angiomatoid fibrous histiocytoma: Unusual sites and unusual morphology. Mod Pathol 2011;24:1560-70.  Back to cited text no. 1
Thway K, Fisher C. Angiomatoid fibrous histiocytoma: The current status of pathology and genetics. Arch Pathol Lab Med 2015;139:674-82.  Back to cited text no. 2
Goldblum JR, Folpe AL, Weiss SW. Chapter 12, Fibrohistiocytic tumors of intermediate malignancy. Enzinger and Weiss's Soft Tissue Tumors. 6th ed. Philadelphia: Elsevier Saunders; 2014. p. 387-420.  Back to cited text no. 3
Enzinger FM. Angiomatoid malignant fibrous histiocytoma: A distinct fibrohistiocytic tumor of children and young adults simulating a vascular neoplasm. Cancer 1979;44:2147-57.  Back to cited text no. 4
Rekhi B, Adamane S, Ghodke K, Desai S, Jambhekar NA. Angiomatoid fibrous histiocytoma: Clinicopathological spectrum of five cases, including EWSR1-CREB1 positive result in a single case. Indian J Pathol Microbiol 2016;59:148-52.  Back to cited text no. 5
[PUBMED]  [Full text]  
Saito K, Kobayashi E, Yoshida A, Araki Y, Kubota D, Tanzawa Y, et al. Angiomatoid fibrous histiocytoma: A series of seven cases including genetically confirmed aggressive cases and a literature review. BMC Musculoskelet Disord 2017;18:31.  Back to cited text no. 6
Tanas MR, Rubin BP, Montgomery EA, Turner SL, Cook JR, Tubbs RR, et al. Utility of FISH in the diagnosis of angiomatoid fibrous histiocytoma: A series of 18 cases. Mod Pathol 2010;23:93-7.  Back to cited text no. 7
Thway K, Gonzalez D, Wren D, Dainton M, Swansbury J, Fisher C. Angiomatoid fibrous histiocytoma: Comparison of fluorescence in situ hybridization and reverse transcription polymerase chain reaction as adjunct diagnostic modalities. Ann Diagn Pathol 2015;19:137-42.  Back to cited text no. 8
Costa MJ, Weiss SW. Angiomatoid malignant fibrous histiocytoma. A follow-up study of 108 cases with evaluation of possible histologic predictors of outcome. Am J Surg Pathol 1990;14:1126-32.  Back to cited text no. 9
Zaccarini DJ, Naous R, Sheth Y, El-Zammar O, de la Roza G, Curtiss CM. TLE-1-positive angiomatoid fibrous histiocytoma mimicking synovial sarcoma. Appl Immunohistochem Mol Morphol 2019;27:e1-4.  Back to cited text no. 10
Kosemehmetoglu K, Vrana J, Folpe A. TLE1 expression is not specific for synovial sarcoma: A whole section study of 163 soft tissue and bone neoplasms. Mod Pathol 2009;22:872-8.  Back to cited text no. 11

Correspondence Address:
Garima Durga
Department of Pathology, Rajiv Gandhi Cancer Institute and Research Centre, Sector V, Rohini, Delhi - 110 085
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpm.ijpm_1468_20

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