Pulmonary artery angiomatoid fibrous histiocytoma mimicking pulmonary embolism

  1. Mian Zeeshan Munir 1,
  2. Ethan Bernstein 2,
  3. Roxanne Wadia 2 and
  4. William B Laskin 2
  1. 1 Hospice and Palliative Medicine, EVMS, Norfolk, Virginia, USA
  2. 2 Yale New Haven Health System, New Haven, Connecticut, USA
  1. Correspondence to Dr Mian Zeeshan Munir; mianmunir809@gmail.com

Publication history

Accepted:28 Feb 2023
First published:29 Mar 2023
Online issue publication:29 Mar 2023

Case reports

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Abstract

A young man presented to the emergency department with pleuritic chest pain and shortness of breath. Of note, he recently went on a long-distance flight of about 9 hours. Given his recent long-distance travel and clinical symptoms, a pulmonary embolism was suspected. However, pathological examination of the excised pulmonary artery intraluminal mass demonstrated an angiomatoid fibrous histiocytoma. This case describes the clinicopathological and immunohistochemical features and molecular profile of a rare type of pulmonary artery tumour, a pulmonary artery angiomatoid fibrous histiocytoma.

Background

Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue neoplasm of intermediate biological potential that commonly arises in the superficial soft tissue of the extremities of children and young adults.1 AFH occurring in the pulmonary parenchyma is a rare tumour with about 14 cases reported in literature.2 Intraluminal pulmonary artery AFH is even more rare with only three previously reported cases in the English-language literature.3–5

We document the fourth case of intraluminal pulmonary artery AFH reported in the English-language literature.

Case presentation

A man in his 20s presented to the emergency department (ED) with acute-onset pleuritic chest pain and shortness of breath. He recently had a long 9-hour flight. He had received his coronavirus vaccine 2 weeks prior to presentation. He had never smoked and had no medical history. Upon arrival to the ED, he was afebrile with a heart rate of 83 beats/min, blood pressure of 143/82 mm Hg, oxygen saturation of 99% and respiratory rate of 18. Physical examination did not reveal any abnormality.

Investigations

Bloodwork revealed normal basic metabolic panel with a creatinine of 1.13 mg/dL (normal: 0.7–1.30), normal brain natriuretic peptide, haemoglobin of 116 g/L (normal: 130–170 g/L), thrombocytosis with platelet count of 421x109/L (normal: 140 –400) and elevated D-dimer 0.54 mg/L FEU-Fibrinogen Equivalent Unit (normal <0.49). ECG demonstrated an isolated ST-segment elevation in lead V3. Given his presentation, risk factors and elevated D-dimer, CT angiography (CTA) was done. The preliminary report revealed a lobulated filling defect in the left main pulmonary artery consistent with pulmonary embolism (PE). However, the final report of the CTA described a 3.4 cm mediastinal mass compressing on the pulmonary artery and resulting in a 95% narrowing of the artery lumen (figure 1). A transthoracic echo revealed normal right and left ventricular function and the presence of a mass abutting the left atrium.

Figure 1

CT angiography showing filling defect in the pulmonary artery.

MRI of the chest showed a heterogeneously enhancing, partially necrotic 3.3 cm soft tissue mass located mostly inside the left pulmonary artery and extending into the mediastinum anterior to the left mainstem bronchus (figure 2).

Figure 2

MRI of the chest with contrast showing a large necrotic mass in the pulmonary artery.

Differential diagnosis

For any patient who presents with shortness of breath, pleuritic chest pain, recent long-distance travel and positive D-dimer, PE is on top of the differential, as was for our patient. Pulmonary artery intraluminal tumours can easily be misdiagnosed as PE, only to be diagnosed during thrombectomy or at autopsy. Intraluminal tumours include pulmonary artery sarcomas, primary myxoid pulmonary tumours or rarely AFH or lung cancer, intra-arterial extension or even with external compression of the pulmonary artery. Diagnosis for the intraluminal tumour would be based on histology, immunohistochemical profiling, and, if needed, molecular evaluation as in our case.

Outcome and follow-up

A pulmonary artery sarcoma was the main consideration on the needle core biopsy based on the intra-arterial location and the presence of atypical cells suspended in a myxoid stroma. The resection specimen demonstrated an intraluminal mass within the dilated lumen of the pulmonary artery (figure 3). Microscopically, the tumour consisted of cellular nodules of plump spindled and epithelioid histiocyte-like cells with mildly atypical oval and retiform nuclei, lightly eosinophilic cytoplasm and ill-defined cytoplasmic borders within a partially myxoid and haemorrhagic stroma (figure 4). Mitotic activity peaked at 4 mitoses in 50 high-powered fields and the Ki-67 proliferative index was approximately 5% (low). Small foci of tumorous necrosis were observed. Notably, the process was well marginated and partially surrounded by a fibrous pseudocapsule and a brisk lymphoplasmacytic infiltrate (figure 5). Immunohistochemically, the tumour cells variably expressed CD99 and ALK-1, focally expressed CD68 and CD34, and exhibited very focal expression of desmin. Tumour cells were negative for smooth muscle actin, EMA, S100 protein and D2-40. EWSR1 gene rearrangement was detected by ‘break-apart’ FISH(Fluorescence In Situ Hybridization). SYT gene rearrangement and MDM2 amplification were not detected by FISH. The characteristic histological findings coupled with the immunoprofile and molecular results confirmed the diagnosis of an AFH arising within the pulmonary artery.

Figure 3

Cut surface of tumour within the pulmonary artery. The tumour is bivalved to reveal a cavity filled with haemorrhagic material. The remainder of the tumour is homogeneous soft and tan-yellow in colour.

Figure 4

H&E, 200×. Nodules display ovoid and spindled tumour cells with myxoid stroma, mild atypia and very low mitotic index.

Figure 5

H&E, 40×. Low-power magnification showing dense fibrous pseudocapsule and nodules of tumour cells with lymphoplasmacytic cuffing.

He subsequently underwent staging CT of the abdomen and pelvis, which did not show any evidence of metastatic disease. The patient remained stable throughout with complete resolution of symptoms. He was discharged with outpatient follow-up with cardiothoracic surgery and oncology and has not experienced a recurrence during a 12-month follow-up interval.

Discussion

AFH is a rare soft tissue neoplasm. It was first reported by Enzinger in 1979 as a subtype of ‘malignant fibrous histiocytoma’ (undifferentiated pleomorphic sarcoma) occurring in the soft tissues of the extremities and less often head and neck and trunk in children and young adults.6 A subsequent larger series by Costa and Weiss found a less aggressive neoplasm than initially thought and the tumour was reclassified as a fibrous histiocytoma with an intermediate risk for recurrence and low metastatic potential.7

Primary pulmonary AFH and especially pulmonary artery AFH are rare occurrences with very cases reported to date. Table 1 compares the three case reports of pulmonary artery AFH published to date in the English-language literature alongside our case.

Table 1

Comparison of cases in literature with our case

Age (years) Sex Presentation Follow-up
Case 1: Ghigna et al 3 70s Female Fever, fatigue and weight loss Clinical recovery and resolution of symptoms after complete resection; no specific timeline given for follow-up
Case 2: Mishima et al 4 40s Male Incidental lung mass on CT of the chest Complete surgical resection; no recurrence at 6-month follow-up
Case 3: Farag et al 5 60s Female Dyspnoea led to an initial clinical diagnosis of PE;
placed on anticoagulation for 3 months; repeat CTPA still showed filling defect; PET scan revealed mass		 Pneumonectomy with removal of mass; complete recovery and no recurrence on follow-up (length of the follow-up interval not defined in the case report)
Munir et al (present case) 20s Male Pleuritic chest pain and shortness of breath Clinical recovery and resolution of symptoms after complete resection; no recurrence at 12-month follow-up

  • CTPA, CT pulmonary angiogram; PE, pulmonary embolism; PET, positron emission tomography.

Given the scarcity of documented cases of pulmonary artery AFH, presenting signs and symptoms and risk factors associated with development of the lesion are not well understood. Symptoms of shortness of breath, chest pain and haemoptysis appear to be associated with the presence of a mediastinal lesion exerting local mass effect. The woman in her 70s with pulmonary artery AFH reported by Ghigna et al 3 presented with non-specific constitutional symptoms. Non-specific systemic symptoms including fever, anaemia and malaise have been reported in patients with AFH and are more frequent in those with visceral tumours.6 7 The more commonly encountered ‘somatic’ AFH mostly presents in children and young adults, but visceral tumours appear to affect an older population,8 as witnessed in our case and in the three previously reported examples of pulmonary artery AFH.

Aetiology of AFH was once a conundrum. The finding that somatic AFH predilects to areas of the body with lymph node aggregates, the vague histological resemblance of the process to a lymph node and desmin expression in nearly 50% of cases suggested to some investigators origin of the process from the fibroblast reticulin cell of the lymph node.9 This hypothesis would not satisfactorily explain visceral or pulmonary artery examples. However, the finding of characteristic gene translocations in the tumour establishes AFH as a translocation-associated neoplasm.

Histologically, AFH is composed of sheets and short fascicles of epithelioid or spindle cells with bland, vesicular nuclei arranged in a multinodular growth pattern with pools of haemorrhage within a fibrosclerotic and partially myxoid stroma. Of note, AFH also typically has a large number of plasma cells (along with lymphocytes). IgG type IV-related disease is also associated with a large number of plasma cells. However, the cellular composition, architecture and the immunoprofile of AFH demonstrate no similarities to IgG type IV-related entities.

Immunohistochemistry is not specific for AFH; however, desmin is expressed in half of these tumours and ALK-1 expression has been observed in nearly 80% of cases.10 Presence of myogenic markers, smooth muscle actin and calponin, and non-specific markers CD99 and CD68 has also been reported. However, keratins, S100 protein, vascular endothelial markers, CD31, CD34, and factor VIII-related antigen, skeletal muscle markers, myogenin and MyoD1, and follicular dendritic cell markers, CD21, CD23 and CD35 are negative. The Ki-67 proliferative index is typically low.4 Genetically, AFH is associated with t(2:22)(q33:q12) (forming the EWSR1–CREB1 fusion gene), 43,44 and less often, t(12:22)(q13:q12) (forming the EWSR1–ATF1 fusion gene) and rarely, t(12:16)(q13:p11) (resulting in the FUS–ATF1 fusion gene).1 The former two translocations are shared by the primary pulmonary myxoid sarcoma.11

The AFH has characteristic pathological features that assist in differentiating the lesion from the main tumours in the differential diagnosis, the intimal sarcoma and AFH’s close congener, the primary pulmonary myxoid sarcoma. Nearly 80% of AFHs are surrounded by a dense lymphoplasmacytic infiltrate,4 which is a feature not yet described in primary pulmonary myxoid sarcoma (figure 5) and, in comparison with the latter neoplasm, the AFH is generally less myxoid. The typically bland cytological appearance of the lesional cells of AFH contrasts sharply with the more high-grade and pleomorphic histological appearance of intimal sarcoma. In addition, the latter neoplasm characteristically demonstrates MDM2 amplification.

Currently, there are no standard guidelines for treatment of pulmonary artery AFH. Complete local surgical resection is the mainstay of therapy. Most AFHs behave relatively indolently. Local recurrence of the lesion is reported in up to 15% of cases1 with higher recurrence rates documented for tumours involving the bone.8 Metastases, reported in less than 5% of cases,1 portend a poorer prognosis.

Learning points

  • A multidisciplinary approach is needed for diagnosis and management of these tumours.

  • Not all pulmonary artery filling defects are pulmonary emboli.

  • Angiomatoid fibrous histiocytoma (AFH) has a classic peritumoral lymphoid cuff, which can help differentiate it from other myxoid tumours.

  • Genetic translocations seen in AFH are characteristic as discussed above.

Ethics statements

Patient consent for publication

Footnotes

  • Contributors MZM conceptualised the case and is the main author. EB assisted with editing. RW assisted with images and editing. WBL is a pathology expert who edited the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • © BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.

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