Extramedullary haematopoiesis presenting as an adnexal mass in a patient with β-thalassaemia

Background

β-thalassaemia is a clinical condition arising from gene mutations affecting β-globin chain production and resulting in inefficient erythropoiesis, chronic transfusion-dependent anaemia and iron overload. Consequently, compensatory extramedullary haematopoiesis (EMH) can arise in different parts of the body. Usually, EMH involves the liver, spleen and paraspinal regions of the thorax.1 EMH involving the adnexa is an extremely rare finding. We report a case with two solid adnexal lesions in a patient affected by β-thalassaemia intermedia (β-TI) diagnosed as EMH trough transvaginal biopsy. Moreover, we present a narrative review of the literature about adnexal EMH in the context of different haematological pathologies. An extensive literature search of PubMed, Cochrane Library and GoogleScholar for articles published to date was performed using the keywords ‘pelvic extramedullary haematopoiesis’, ‘ovary extramedullary haematopoiesis’, ‘ovary myeloid metaplasia’, ‘extramedullary haematopoiesis thalassaemia’ and ‘extramedullary haematopoiesis ultrasound female pelvis’, to collect all studies reporting cases of adnexal EMH. No language restrictions were applied, and reference lists of all included studies were manually searched for other potentially eligible studies. Our search results revealed that no case-control or cohort studies of adnexal EMH have been published. We identified nine published case reports of adnexal EMH (tables 1 and 2). One has been excluded because EMH was not related to a haematological disease.2 Of the included publications, one was available only as an abstract.3

Case presentation

A woman in her 40s, gravida 2, para 1 of Southeast Asian origin, with a history of transfusion-dependent heterozygote β-TI with a compound heterozygosity Beta0/HbE (Deletion c126-129; -CTTT) was referred from haematology to our department of gynaecological ultrasound for the evaluation of two suspicious adnexal lesions. The patient reported that adnexal masses had been observed 4 years earlier during her caesarean delivery and had not been removed, examined nor treated thereafter.

The patient always had a regular cycle; she had no dyspareunia, no dysuria, no dyschezia and did not complain about abdominal pain. She had one spontaneous abortion. A family history of breast and ovarian cancer was denied.

The patient was already known for having EMH in the lungs, as well as in the paravertebral regions, which led to a caudal paraplegic syndrome due to cord compression 3 years before. The lesions regressed after radiation, oral therapy with N-hydroxyurea and regular transfusions with complete regression of the symptomatology. In addition, she had hepatosplenomegaly with hepatic siderosis, suspected functional asplenia and a dilatative cardiopathy.

She was currently on daily treatment with deferasirox 180 mg (2-0-1), an oral tridentate chelator that mobilises iron stores by binding selectively to the ferric form of iron, and N-hydroxyurea 500 mg/day for 4 days a week, an antineoplastic agent and fetal hemoglobin enhancer that increases hemoglobin levels, reduces blood transfusion dependency, decreases skeletal deformities and splenomegaly.

Diagnosis and treatment

The transvaginal ultrasound showed a normal uterus with a homogeneous hypoechogenic endometrium of 7.7 mm. There was a well-circumscribed, isoechogenic to hypoechogenic, inhomogeneous solid mass involving the right ovary measuring 83×87×77 mm (volume 291 mL). Thick hyperechogenic septa divided the lesion in smaller round compartments which were then further subdivided by thinner septa. There were acoustic shadows and normal residual ovarian tissue of 23 mm of length at the outer rim of the mass (figure 1A,B). The blood flow within the solid lesion was moderate (colour score 3) (figure 1C). A smaller second mass measuring 45×28×48 mm (volume 32 mL) with the same sonographic features was observed contiguous to the left ovary (figure 1D). No free fluid was detected in the pouch of Douglas. No further solid lesions were detected intra-abdominally, and there were no signs of pelvic lymphadenopathy.

The tumour marker CA125 was normal (13.9 U/mL). No further tumour marker was determined. We assessed the lesions according to the criteria of the International Ovarian Tumour Analysis (IOTA) group.4 IOTA simple rules were inconclusive, as no benign nor malignant features applied.5 The risk calculation with the IOTA Assessment of Different NEoplasias in the adneXa (ADNEX) model (the only one with the advantage of differentiating between histological subtypes) suggested a benign adnexal tumour, with the highest relative risk (1.3) as well as a patient specific risk of 90.9% for a benign lesion,6 classifying the tumour as Ovarian-Adnexal Reporting & Data System (O-RADS 3) (low risk of malignancy).7 Furthermore, the combination of CA125 and the described ultrasound findings resulted in a low risk of malignancy index (1×3×13.9=41.7).8 The medical history of the patient and the sonographic features as interpreted by expert pattern recognition were suggestive of a possible site of EMH. After an interdisciplinary discussion with the haematologists and the gynaecological oncologists, a transvaginal ultrasound-guided core needle biopsy of the right adnexal mass was performed during the 3-week follow-up scan. The procedure was carried out in the lithotomy position, using a high-resolution endovaginal probe (GE Voluson E10, 7.5–12 MHz) and a core biopsy instrument (Bard Mission Disposable Core Biopsy Instrument 18G×25 cm—semiautomatic). No anaesthesia was needed, and no periprocedural nor postprocedural complications were observed. The patient did not complain about any pain. The tissue obtained was placed in formalin and sent for pathological examination. Histology confirmed the presence of trilinear EMH with a predominance of erythropoiesis and proliferation of eosinophilic granulocytes and megakaryocytes (figure 2A,B). The haematologist and the gynaecological oncologist opted against the removal of the lesions and adnexectomy, as the patient was asymptomatic and has a systemic disease which is already under treatment.

Outcome and Follow-up

Four months after the biopsy ultrasound imaging of the adnexal masses is unchanged. The patient is stable and undergoes regular follow-ups with her haematologist. She is under treatment with luspatercept (recombinant fusion protein that binds transforming growth factor beta) to enhance erythroid maturation and reduce transfusion burden.

Synthesis of the narrative review