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Case Report DOI: 10.13107/jocr.2026.v16.i10.8188 PDF

Angiomatoid Fibrous Histiocytoma in a Child with Hereditary Spherocytosis: A Rare Co-occurrence

Learning Point of the Article:

To the best of our knowledge, this is the first reported case of the rare co-occurrence of AFH in a child with hereditary spherocytosis post-splenectomy. The relationship between hereditary spherocytosis, splenectomy, and the development of AFH is speculative.

, , , , ,
  1. 1 Department of Orthopedics, All India Institute of Medical Sciences, New Delhi, India
  2. 2 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
Address of Correspondence: Dr. Venkatesan Sampath Kumar, Department of Orthopedics, All India Institute of Medical Sciences, New Delhi, India. E-mail: venkatortho04@gmail.com

Received: Accepted: Published:

Copyright: © 2026 Indian Orthopaedic Research Group

Abstract

Introduction:

Angiomatoid fibrous histiocytoma (AFH) is a rare soft-tissue tumor of low malignant potential, and its radiological appearance is often non-specific, mimicking benign cysts, hematomas, or infections, necessitating histopathological and immunohistochemical confirmation. While hematological malignancies have been reported in Hereditary Spherocytosis (HS), no association with AFH has been documented. We present the first case of AFH involving the shoulder soft tissue in a post-splenectomy adolescent with HS, highlighting diagnostic challenges and a possible link between chronic hematologic stress and mesenchymal tumor development.

Case Report:

A child in his early adolescence presented with a 2-month history of right shoulder pain and swelling, which was progressively increasing in size, firm, painful, and associated with fever. His total leukocyte count was 15,500/mm3, and C-reactive protein was 152 mg/L. He had a history of multiple blood transfusions since the age of four. Eight months prior, he was diagnosed with HS and underwent total splenectomy for massive splenomegaly. Magnetic resonance imaging revealed a soft-tissue lesion posterior to the glenoid, abutting the spine of the scapula. A bone scan ruled out an infectious etiology. Ultrasound-guided fine needle aspiration cytology showed no organisms and was negative for malignant cells. Surgical excision of the mass was performed, and histopathology confirmed the diagnosis of AFH.

Conclusion:

This case highlights the importance of considering AFH in the differential diagnosis of soft-tissue tumors in children with hematologic disorders.

Keywords:

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Introduction

Angiomatoid fibrous histiocytoma (AFH) is a soft-tissue neoplasm of low malignant potential, typically involving the superficial soft-tissue of the extremities in children [1]. The World Health Organisation has classified it as a tumor of uncertain differentiation with moderate biological potential and an incidence of 0.3% of all soft-tissue neoplasms [2]. It is a spindle cell or epithelioid tumor surrounded by sleeves of lymphoid tissue in the following areas: Antecubital fossa, axilla, inguinal region, and supraclavicular region [3,4]. It is considered to arise from pluripotent stem cells involving the fusion of the Ewing Sarcoma breakpoint Region 1 gene (EWSR1) and either the cAMP Response Element Binding protein 1 (CREB1) or Activating Transcription Factor 1 (ATF1) gene. An association with other diseases such as human immunodeficiency virus, neuroblastoma, testicular tumors, and Hodgkin’s lymphoma has been reported.

The appearance of AFH on plain radiograph is non-specific: A mass with cystic areas, pseudocapsule, and internal fluid-fluid levels [5]. However, the occurrence of fluid-fluid levels is non-specific, as it may occur in other lesions, such as soft-tissue hemangioma, hematoma, and malignant fibrous histiocytoma. In the reported cases of AFH with soft-tissue involvement, these lesions were indistinguishable from other bone lesions merely on the basis of radiological appearance.

Hereditary spherocytosis (HS) is a common type of hemolytic anemia that can present as intermittent jaundice and splenomegaly. The soft-tissue lymph node swelling in HS can mimic extramedullary hematopoiesis after splenectomy [6]. There are reports of the occurrence of non-Hodgkin lymphoma and chronic myeloid myelocytic leukemia with HS [7,8]. This is a rare case of AFH involving the soft tissue of the shoulder in a post-splenectomy patient with HS; no direct association has been documented previously. Parental consent was taken for the use of patient’s data, radiographic images, and clinical details of the patient.

Case Report

A male child in early adolescence presented with a 2-month history of right shoulder pain and swelling. The swelling progressed from pea-sized to the size of a cricket ball and was painful, with pain exacerbated by shoulder movement. He had a low-grade fever for 5 days, which resolved with medication. There were no systemic symptoms such as loss of appetite, weight loss, trauma, generalized joint involvement, or morning stiffness.

On examination, a single, firm, tender, fluctuant, lobulated swelling measuring 10 × 6 cm was noted in the right periscapular region. It had well-defined margins, raised overlying skin temperature, and no neurovascular deficit.

The patient was born full-term through cesarean section, with a birth weight of 2.6 kg, and was treated in the Pediatric Intensive Care Unit for 7 days for neonatal jaundice. He had a history of multiple transfusions from age four for undiagnosed anemia. Eight months prior, he presented with pallor, jaundice, generalised weakness, intermittent breathlessness, and abdominal distension. He was diagnosed with HS and underwent splenectomy for massive splenomegaly.

Investigations

  • -> Laboratory studies revealed leukocytosis (15,500/mm3) and elevated C-reactive protein (152 mg/L)

  • -> A plain radiograph did not reveal any lytic or sclerotic lesion

  • -> Magnetic resonance imaging (MRI) revealed a multiloculated lesion with T1 hypointensity and T2 hyperintensity, surrounded by a pseudocapsule – features suggestive of a complex cystic neoplasm or hematoma (Fig. 1)

  • -> A bone scan ruled out an infectious pathology

  • -> Fine-needle aspiration was inconclusive. No organisms grew on the culture.

Figure 1: The magnetic resonance imaging shows a large expansile multi-loculated space occupying the lesion, abutting the spine of the scapula and encasing the glenohumeral joint posteriorly.
Figure 1: The magnetic resonance imaging shows a large expansile multi-loculated space occupying the lesion, abutting the spine of the scapula and encasing the glenohumeral joint posteriorly.

Differential diagnosis

  • -> AFH

  • -> Synovial sarcoma

  • -> Malignant peripheral nerve sheath tumor (MPNST)

  • -> Hydatid cyst

  • -> Pseudotumor

  • -> Extramedullary hematopoiesis.

Table 1 compares the features of the differential diagnosis.

Table 1

Features differential diagnosis of AFH

Feature Angiomatoid fibrous histiocytoma Synovial sarcoma Malignant peripheral nerve sheath tumor Hydatid cyst
Etiology Neoplastic Ewing sarcoma breakpoint region 1- Element Binding protein 1 gene fusion Malignant–t(X;18) translocation (SYT-SSX fusion) Malignant-often associated with Neurofibromatosis Type 1 (NF1) Parasitic infection (Echinococcus)
Clinical features Slow-growing, painless mass in children and adolescents in extremities. Slow-growing mass in adolescent and adults near large joints, initially painless later can present with pain. Rapidly growing painful mass near nerve trunks in adults, associated with numbness and parasthesia Any age patient living in endemic region of echinococcus±allergic reactions secondary to rupture of cyst.
MRI Findings Well-circumscribed, multiloculated, T1 hypointense, T2 hyperintense with fluid-fluid levels, thick pseudocapsule, internal septations Heterogeneous with cystic/solid areas and septations; may calcify; possible hemorrhage Ill-defined, heterogeneous; necrosis; fusiform shape along nerve trajectory Multiloculated cyst with daughter cysts, T2 hyperintense with hypointense rim (“hydatid sand”).
Histopathology Pseudoangiomatous blood-filled cystic spaces, fibrous pseudocapsule, spindle-epithelioid cells, lymphoid cuff, hemosiderin Monophasic (spindle cells) or biphasic (spindle+epithelial); glandular or cystic patterns possible Hypercellular spindle cells, high mitoses, necrosis, and alternating hypo- and hypercellular areas Laminated ectocyst and germinal endocyst; surrounding inflammatory cells with eosinophils

Treatment

An open excisional biopsy with wide resection was performed. Intraoperatively, a well-encapsulated mass was identified and excised in total. Histopathology revealed multiple blood-filled cystic spaces lined by spindle and epithelioid cells with hemosiderin and lymphocytic infiltrate, with tumor-free margins, suggestive of AFH. Immunohistochemistry showed epithelial membrane antigen (EMA+), desmin+, and cluster of differentiation (CD)99 (focal)+, consistent with AFH (Fig. 2).

Figure 2: It shows the pathological appearance of the specimen. Hematoxylin and eosin (HE) stain section shows blood-filled cystic spaces with fibrous walls containing lymphoid follicles (arrows) and brownish pigments (a), HE ×40). In addition, there are sheets of tumor cells with infiltrating borders (black arrows) (b), HE ×100). The tumor cells have epithelioid to spindle cell morphology with vesicular nuclei, inconspicuous nucleoli, and a scant to moderate amount of eosinophilic cytoplasm. Hemosiderin deposition is present (c), HE ×400). Tumor cells are diffusely immune positive with desmin (d), ×200).
Figure 2: It shows the pathological appearance of the specimen. Hematoxylin and eosin (HE) stain section shows blood-filled cystic spaces with fibrous walls containing lymphoid follicles (arrows) and brownish pigments (a), HE ×40). In addition, there are sheets of tumor cells with infiltrating borders (black arrows) (b), HE ×100). The tumor cells have epithelioid to spindle cell morphology with vesicular nuclei, inconspicuous nucleoli, and a scant to moderate amount of eosinophilic cytoplasm. Hemosiderin deposition is present (c), HE ×400). Tumor cells are diffusely immune positive with desmin (d), ×200).

Outcome and follow-up

At a 3-year follow-up, the patient had no recurrence and regained moderate shoulder mobility. He had the following range of motion in his shoulder: Forward flexion 70°, extension 30°, abduction 90°, adduction 20°, external rotation 80°, and internal rotation 90° (Fig. 3). He had a Musculoskeletal Tumor Society score-93 of 66.67 % and a Quick Disability of Arm Shoulder and Hand score of 20.5% at the 3 years follow-up. An algorithm for the evaluation and management of soft-tissue swelling in post-splenectomy patients with hemolytic anemia is presented in Flow Chart 1.

Figure 3: It depicts the moderate functional recovery of the shoulder at the 3-year follow-up.
Figure 3: It depicts the moderate functional recovery of the shoulder at the 3-year follow-up.
Flow Chart 1: Management algorithm for soft-tissue swellings in post-splenectomy patients with hemolytic anemia.
Flow Chart 1: Management algorithm for soft-tissue swellings in post-splenectomy patients with hemolytic anemia.

Discussion

AFH is a rare soft-tissue neoplasm first described by Enzinger in 1979 while studying 42 cases of unusual fibro-histiocytic sarcoma, in which the median age was 13 years [9]. It is a unique tumor that blends clinical, radiologic, and histologic ambiguity. Its imaging appearance often suggests hematomas, benign vascular lesions, cystic-necrotic lesions, and calcifying lesions [10]. Radiological mimicry of an infectious etiology frequently confuses the diagnosis, emphasizing the need for tissue biopsy [11]. In our case, we considered infective foci as differential diagnosis due to raised inflammatory markers after splenectomy, while MRI suggested a cystic collection or pseudotumor.

Histologically, AFH is characterized by pseudoangiomatous spaces, fibrous pseudocapsule, chronic inflammatory infiltrate, and hemosiderin-laden macrophages [12]. Immunohistochemistry typically demonstrates EMA and desmin positivity, with variable CD99, and is negative for S100 and cytokeratin, helping differentiate it from MPNST, rhabdomyosarcoma, and synovial sarcoma [13]. In our case, aspiration was inconclusive, but histopathological features of spindle and epithelioid cells with hemosiderin and lymphocytic infiltrate were suggestive of AFH. Immunohistochemistry staining supplemented the diagnosis by EMA+, desmin+, and CD99 (focal)+. Gene fusion testing can provide diagnostic confirmation, especially in ambiguous cases, though it was not available in our setting. Recent reviews emphasize the utility of next-generation sequencing or reverse transcription polymerase chain reaction for EWSR1-CREB1 or ATF1 fusions [3]. Surgery is the mainstay of management, with an excellent prognosis when primary complete excision is achieved [13]. While AFH is mostly indolent, it carries a local recurrence risk of 15–20% and a rare metastatic potential of 1–3% [14]. Adjuvant radiotherapy or chemotherapy may be considered when excision is incomplete or in the presence of distant metastasis [15,16]. Wide local excision with negative margins remains the cornerstone of treatment. We did not observe local or distant recurrence at the 3 years of follow-up.

HS is a common cause of hemolytic anemia in children and results from disruption of the red blood cell membrane. The development of a swelling could be due to an extramedullary hematopoiesis in a splenectomized patient with HS [18]. The prolonged erythropoietin stimulation might play an etiological role in some of these patients. These tumors contain a more copious fat component than usual hematopoietic tumors. Extramedullary hematopoiesis was reported in various parts of the body in HS, ranging from lymph nodes, pleura, and mediastinum to adrenal glands and liver. Other tumors have also been reported in HS, including B-cell lymphoma, acute lymphoblastic leukemia (ALL), and pancreatic schwannoma [19–21]. Our case was unique because the soft-tissue mass adjacent to the scapula that could be confused with extramedullary hematopoiesis. It could be postulated that erythropoietin played some role in the development of the tumor in this patient. Our case is unique for its co-occurrence with HS and post-splenectomy. While previous reports describe HS patients developing hematologic malignancies such as acute myeloid leukemia (AML) or chronic myeloid leukemia (CML) [8,22], no association with AFH has been described to date. The patient’s chronic erythroid stress and post-splenectomy immune modulation could theoretically create a permissive microenvironment for mesenchymal transformation, though this remains speculative.

There have been reports suggesting an association between AFH and leukemia, lymphoma, and platelet disorders [8,23,24,25]. Given that a soft-tissue tumor has been linked to two blood cell lineages, it is worth considering whether a similar association could exist with the third lineage- erythrocytes. In our case, we noted a connection between AFH and a condition involving red blood cells, though this observation remains preliminary and requires further investigation. This case thus expands the clinical spectrum of AFH and raises the possibility of a link between chronic hematologic stress and mesenchymal tumorigenesis, warranting further research.

Conclusion

AFH can mimic benign or infective lesions radiologically, making histopathology essential for diagnosis. Immunohistochemistry (EMA+, desmin+, focal CD99+) is critical in differentiating AFH from sarcomas. This is the first reported case of AFH in a child with HS after splenectomy. The development of AFH in this setting suggests a possible but as yet unproven link between chronic hematologic stress, immune modulation, and mesenchymal tumorigenesis. Wide local excision with close surveillance may provide acceptable outcomes, given the recognized risk of local recurrence associated with AFH.

Clinical Message

This is the first reported case linking AFH to hereditary spherocytosis, expanding its clinical spectrum, and immunohistochemistry plays a critical role in confirming the diagnosis. Therefore, AFH should be considered in the differential diagnosis of soft-tissue swelling in post-splenectomy patients with HS.

Conflict of Interest:

Nil

Source of Support:

Nil

Consent

The authors confirm that informed consent was obtained from the patient for publication of this article

How to Cite this Article

Sehrawat S, Kumar VS, Kapoor L, Mridha AR. Angiomatoid Fibrous Histiocytoma in a Child with Hereditary Spherocytosis: A Rare Co-occurrence. Journal of Orthopaedic Case Reports 2026 October;16(10): 63-68.

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© 2026 Journal of Orthopaedic Case Reports - Published by Indian Orthopaedic Research Group

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How to cite this article: Sehrawat S, Kumar VS, Kapoor L, Mridha AR, Yadav D, Khan SA. Angiomatoid Fibrous Histiocytoma in a Child with Hereditary Spherocytosis: A Rare Co-occurrence. J Orthop Case Rep. 2026 Oct;16(10):63-68. doi:10.13107/jocr.2026.v16.i10.8188

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