Angiomatoid fibrous histiocytoma is a rare soft tissue tumor usually discovered in young individuals. This tumor is often mistaken for a hematoma and typically misdiagnosed. It is commonly found in the extremities and may be associated with a site of recent or previous trauma. Characteristic histology includes nodules of histiocytoid spindle cells with pseudoangiomatoid spaces, fibrous pseudocapsules, and lymphoid cuffing. We describe the case of an 8-year-old girl who presented after incision and drainage of a superficial thigh lesion and experienced subsequent chronic bleeding of her wound. Her initial presentation was concerning for an underlying bleeding disorder, and laboratory analysis uncovered a paraneoplastic platelet function disorder that resolved with therapy of the primary tumor.

Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor commonly found in children, adolescents, and young adults.1 The preoperative diagnosis of AFH is difficult without the aid of pathologic or radiologic evaluation. Regional symptoms such as pain and tenderness are uncommon, but AFH has been associated with weight loss, anemia, and pyrexia secondary to production of inflammatory mediators.1 Immunohistochemical and cytogenetic features are commonly relied on to confirm the diagnosis. The curative therapy is surgical excision with margins negative for AFH. We present the case of a preadolescent girl without a significant bleeding history who experienced prolonged bleeding after incision and drainage of a presumed hematoma. Complete surgical excision led to a diagnosis of AFH as well as resolution of a novel secondary paraneoplastic platelet function disorder.

An 8-year-old girl was transferred to our institution from a community hospital for evaluation of chronic iron deficiency anemia secondary to a left thigh incision and drainage wound with chronic bleeding. She had a 5-month history of left thigh hematoma discovered after striking her thigh against a coffee table. The hematoma was initially the size of a quarter, but continued to enlarge to several centimeters in diameter. Three months after her injury, she was evaluated by a general surgeon who performed an incision and drainage with drain placement. The drain was left in place for ∼7 days after the procedure and then removed, but bleeding from the site continued, requiring several daily dressing changes over a nonhealing wound. Because of the bleeding, her pediatrician was monitoring her hemoglobin (Hb), and 2 weeks before admission at our institution, her Hb level was 7.4 g/dL and she was started on daily oral iron supplementation. Her Hb levels continued to decrease, leading to admission at an outside hospital for anemia secondary to blood loss and iron deficiency. At this facility, her complete blood cell count showed a white blood cell count of 8.4 × 103 cells/µL, an Hb level of 6.6 g/dL, a hematocrit of 22.3%, platelet levels of 602 000/μL, and a reticulocyte count of 1.3%. Results of iron studies revealed iron levels of 10 µg/dL, a total iron binding capacity of 222 µg/dL, ferritin levels of 250 ng/mL, and a haptoglobin level of 624 mg/dL. The lactate dehydrogenase level was 362 U/L. The international normalized ratio was 1.3; prothrombin time and partial thromboplastin time were prolonged at 16.2 and 40.8 seconds, respectively. Testing with a platelet function analyzer (PFA-100) revealed collagen/epinephrine and collagen/adenosine diphosphate (ADP) membrane closure times that were both more than 300 seconds. She received 2 Us of packed red blood cells and 3 days of intravenous iron while admitted. A computed tomography scan of the abdomen, pelvis, and lower extremities with contrast was performed that revealed “an oval subcutaneous mass in left anterior lateral proximal thigh that extended to skin surface with heterogeneous appearance with fluid in the inferior caudal aspect and ipsilateral inguinal enlarged lymph nodes.” She was transferred to our facility for further evaluation of a possible bleeding disorder.

Her birth history was significant for pregnancy complicated by gestational diabetes mellitus. She was a term newborn via vaginal delivery and required 2 weeks of phototherapy for jaundice. Her newborn screen was normal. Surgical history was significant for tonsillectomy and adenoidectomy at 3 years of age without complications. The patient lived with her parents and there was no previous history of a bleeding disorder or bleeding after accidental injuries. There was no recent travel and immunizations were up to date. Family history was only significant for coronary artery disease on the maternal side of the family. She had no history of fever, fatigue, night sweats, or weight loss. On examination, she was afebrile with normal blood pressure and peripheral pulses. She appeared pale and had a grade II/VI systolic murmur at the left upper sternal border. There was no significant lymphadenopathy on palpation. Her left lateral thigh had a ulcerated wound measuring ∼1 × 1 cm with surrounding erythema extending ∼6 cm in diameter and a superficial induration lateral to the wound. The remainder of examination was normal. An MRI of the left lower extremity was performed that showed an enhancing lesion in the subcutaneous soft tissues of the anterolateral left thigh characterized by a small fluid component with a focal breach of the fascia and a small extension into the deep soft tissues (Fig 1 A and B).

FIGURE 1

MRI of thighs with and without contrast. A, coronal view. B, axial view. The oval-shaped lesion in superficial subcutaneous soft tissues of the anterolateral left mid-thigh measuring ∼5 cm craniocaudal × 3.2 cm wide × 3 cm anteroposterior is shown. The breach of the fascia with a focal extension of fluid component of the lesion into tissues adjacent to the fascia is also shown.

FIGURE 1

MRI of thighs with and without contrast. A, coronal view. B, axial view. The oval-shaped lesion in superficial subcutaneous soft tissues of the anterolateral left mid-thigh measuring ∼5 cm craniocaudal × 3.2 cm wide × 3 cm anteroposterior is shown. The breach of the fascia with a focal extension of fluid component of the lesion into tissues adjacent to the fascia is also shown.

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Laboratory studies at our facility showed a complete metabolic panel with elevated total protein (8.5 gm/dL) and decreased albumin (3.4 gm/dL); the panel was otherwise normal. Repeat hematology and coagulation laboratory testing was performed at our facility and is depicted in Table 1. Acute inflammatory markers were elevated (erythrocyte sedimentation rate of 113 mm/hour; C-reactive protein level of more than 270 mg/L). The ristocetin cofactor and factors V, X, and XIII were at normal levels. Von Willebrand multimeric analysis yielded abnormal results, with an absence of multimers of the highest molecular weight. A wound culture was obtained and grew methicillin-sensitive Staphylococcus aureus, and the patient was treated with a 14-day course of clindamycin. Urine protein electrophoresis demonstrated a chronic inflammatory pattern along with elevated immunoglobulin G (2000 mg/dL) and immunoglobulin M (250 mg/dL) levels. A peripheral blood smear showed enlarged platelets. Formal platelet aggregation studies showed decreased platelet aggregation with collagen and normal aggregation with other agonists (ADP and ristocetin) in addition to normal collagen and thrombin secretion. In addition, platelet glycoprotein expression was normal, but platelet electron microscopy revealed results consistent with a δ granule storage pool deficiency of 1.71 δ granules per platelet (normal range: 4–6 δ granules per platelet).

TABLE 1

Relevant Pre- and Postsurgical Hematology and Coagulation Laboratory Results

Presurgical Hematology and Coagulation Laboratory Results (on Admission)Postsurgical Hematology and Coagulation Laboratory Results (1 mo After Discharge)
White blood cell count, cells/µL 10.4 × 103 6.9 × 103 
Hb, g/dL 8.8 12.8 
Hematocrit, % 28.3 38.7 
Platelet count, per μL 586 000 316 000 
Mean corpuscular volume, fL 68.9 76.5 
International normalized ratio 1.3 0.9 
Prothrombin time, s 13.5 9.7 
Partial thromboplastin time, s 37.9 27.6 
Fibrinogen, mg/dL 906 — 
Thrombin time, s 17.9 — 
Factor VIII, % 238 — 
Factor VIII related antigen, % >149 >150 
Factor IX, % 202 — 
PFA-100 collagen/epinephrine closure time, s >300 107 
PFA-100 collagen/ADP closure time, s >300 74 
Presurgical Hematology and Coagulation Laboratory Results (on Admission)Postsurgical Hematology and Coagulation Laboratory Results (1 mo After Discharge)
White blood cell count, cells/µL 10.4 × 103 6.9 × 103 
Hb, g/dL 8.8 12.8 
Hematocrit, % 28.3 38.7 
Platelet count, per μL 586 000 316 000 
Mean corpuscular volume, fL 68.9 76.5 
International normalized ratio 1.3 0.9 
Prothrombin time, s 13.5 9.7 
Partial thromboplastin time, s 37.9 27.6 
Fibrinogen, mg/dL 906 — 
Thrombin time, s 17.9 — 
Factor VIII, % 238 — 
Factor VIII related antigen, % >149 >150 
Factor IX, % 202 — 
PFA-100 collagen/epinephrine closure time, s >300 107 
PFA-100 collagen/ADP closure time, s >300 74 

—, not obtained.

On hospital day 5, surgical excision with drain placement was conducted, pathology evaluation of the excised specimen was performed, and fungal and bacterial cultures were obtained. Surgical pathology and fluorescence in situ hybridization analysis revealed evidence of an Ewing sarcoma breakpoint region 1 (22q12) gene rearrangement in ∼64.5% of cells, consistent with a translocation of the Ewing sarcoma breakpoint region 1 gene and diagnosis of AFH (Figs 2 and 3). A bone scan and chest computed tomography scan revealed normal results and ruled out metastatic disease. The medial margins of the pathology specimen were positive for AFH, so the patient had a reexcision of the remaining tumor on hospital day 10. Margins were clear after reexcision and all specimen cultures were negative for bacterial and fungal organisms. She was discharged on hospital day 14 in good condition.

FIGURE 2

Microscopic findings of AFH demonstrating a nodular proliferation of spindled and histiocyte-like cells arranged in sheets with microscopic hemorrhage and inflammatory changes.

FIGURE 2

Microscopic findings of AFH demonstrating a nodular proliferation of spindled and histiocyte-like cells arranged in sheets with microscopic hemorrhage and inflammatory changes.

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FIGURE 3

Immunohistochemical staining with desmin demonstrating presence of myoid differentiation.

FIGURE 3

Immunohistochemical staining with desmin demonstrating presence of myoid differentiation.

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At follow-up, 1 month after discharge, she was clinically well and the excision site had healed. Repeat coagulation studies postsurgery normalized and are depicted in Table 1. Six months after surgical excision, an MRI showed no evidence of local recurrence.

Enzinger originally described AFH in the literature in 1979. He noted that AFH primarily occurred in the extremities of young individuals. Precedent trauma was noted in several initial cases of the lesion, and the tumor was often mistaken for a hematoma or hemangioma.2 The diagnosis of AFH is often missed because of the rarity of this tumor and initial misdiagnosis of the lesion.3 AFH may only rarely metastasize to local lymph nodes and is highly unlikely to demonstrate distant site metastases.4 Some patients may experience systemic symptoms including anemia, weight loss, and malaise.4,6 It has been observed in the literature that AFH can present with paraneoplastic symptoms, and this tumor has arisen from unusual sites, such as bone.7 Our patient presented with a microcytic, hypochromic anemia consistent with iron deficiency anemia. This finding was likely secondary to chronic bleeding associated with δ storage pool platelet dysfunction and a nonhealing wound and not to AFH systemic effects. It is known that in addition to platelet aggregation, the dense granules in platelets promote wound repair, and so her delayed wound healing was likely multifactorial.8 Dense granule storage pool deficiency has been associated with defects in prothrombinase, adenosine triphosphate and ADP secretion, and serotonin as well as with decreased intracellular calcium. Platelet aggregation is impaired secondary to these defects.9 Dense granule storage pool deficiency can present with symptoms such as easy bleeding and bruising, menorrhagia, anemia, and abnormal bleeding after surgery, dental work, or childbirth. Storage pool disorders can be inherited or acquired and have been associated with congenital conditions such as Hermansky-Pudlak syndrome, thrombocytopenia absent radii syndrome, and Wiskott-Aldrich syndrome.10,13 

Her platelet dysfunction resolved after complete tumor excision, indicating that the storage pool disorder was likely an acquired paraneoplastic condition and not an inherited bleeding tendency. Akiyama et al14 postulated the possibility of increased interleukin-6 in AFH cells contributing to paraneoplastic syndrome after improvement of laboratory findings, including anemia, after tumor resection. It is important to note that anemia can prolong PFA-100 closure times.15 It is possible that increased local inflammatory cytokines could have produced systemic hemostasis and coagulation abnormalities. Unfortunately, repeat PFA-100 testing after surgery could not be performed because of cost restrictions. This case shows a unique clinical presentation that required extensive hemostasis evaluation and a histopathology confirmation of the diagnosis.

After complete surgical excision of AFH, there is a risk of local recurrence of disease (23.2%) and a small (8.7%) risk of metastatic recurrence within 24 months after excision.6 Taking these data into consideration, there is a low probability of metastasis, but our patient will require close follow-up in case of local recurrence.

We report a unique case of AFH associated with paraneoplastic dense granule platelet storage pool deficiency in a female child after precedent trauma. Although her trauma may have been coincidental, it may have initiated an inflammatory response at the local site of the tumor, causing increased inflammation and edema. Unfortunately, the patient’s family elected not to have additional PFA-100 or platelet electron microscopy testing performed after surgical excision on the basis of cost and lack of insurance coverage. To our knowledge, there have been no other reported cases of AFH associated with platelet storage pool deficiency.

     
  • ADP

    adenosine diphosphate

  •  
  • AFH

    angiomatoid fibrous histiocytoma

  •  
  • Hb

    hemoglobin

Dr Morgan conceptualized the case report, drafted the manuscript, and reviewed and revised the manuscript; Drs Miller, Raj, Coventry, and Elster aided in conceptualizing, revising, and reviewing the manuscript; and all authors contributed significantly to the conception, drafts, and final case report manuscript, reviewed the figures and data for accuracy, and approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

FUNDING: No external funding.

The authors would like to thank Ms Tiffney Gipson for literature review assistance.

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Competing Interests

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.