ALK-positive anaplastic large cell lymphoma of skeletal muscle masquerading as soft tissue sarcoma

Background

Anaplastic large cell lymphoma (ALCL) constitutes 2%–8% of all adult non-Hodgkin’s lymphomas (NHLs) and up to 30% of all paediatric NHLs. It was first described by Stein et al in 1985 and is characterised by the proliferation of anaplastic lymphoid cells having large pleomorphic lymphoid cells, often having the variable number of ‘hallmark cells’ represented by irregular horseshoe-shaped nuclei.1 ALCL can involve extranodal sites, including soft tissue, skin, bone, lungs and liver.2 Because of the cohesive growth pattern and marked cytomorphological variation noted in the cells of ALCL, a range of non-haematological malignancies such as carcinomas, sarcomas, germ cell tumours and melanomas can enter into the differential diagnosis, particularly in the extranodal sites. ALCL involvement of skeletal muscle is infrequent, and a few cases have been reported in the literature.3 4 Herein, a case of ALCL of extranodal site mimicking high-grade sarcoma is presented.

Case presentation

A 12-year-old male child presented to the outpatient clinic with insidious onset swelling in the medial side of the left upper thigh (figure 1A). The swelling measured 13×10 cm and was painless and gradually progressive for 1.5 months. However, it became painful for the last 5 days. He also had another swelling in the anterior chest wall for 1 month, measuring 12×10 cm (figure 1B). The skin over the swellings was excoriated with areas of reddish discolouration. Both the swellings were tender, firm, non-fluctuant, non-compressible and non-pulsatile. There was no significant medical history. On physical examination, he was afebrile and had a pulse rate of 118/min and respiratory rate of 22/min. There was no pallor, icterus, cyanosis, clubbing or oedema. Left inguinal lymphadenopathy was present, which was subcentimetric, mobile and non-tender; however, no axillary or cervical node enlargement was noted.

The MRI showed a large well-defined lobulated heterogeneously hyperintense (T2) and hypointense (T1) signal lesion in the muscular plane (invading adductor longus, magnus muscles and abutting sartorius, gracilis, semimembranous, semitendinosus muscles, long head of biceps tendon and distal part of superficial femoral vessels) at the medial aspect of the left mid-distal thigh. On CT of chest mass, a heterogeneously enhancing solid mass lesion measuring 8×6.6×8 cm was seen at the upper anterior mediastinum with extrathoracic chest wall components. The intrathoracic mediastinal components showed loss of fat plane with upper mediastinal vessels, superior vena cava, arch of aorta, pulmonary trunk and trachea. The external chest wall swelling extended from right upper anterior part of the chest wall through the sternal region of the chest wall causing subtle erosion of the inner table of the manubrium. The mass showed heterogeneously enhancing solid areas with central non-enhancing necrotic areas.

The fine needle aspiration cytology from both chest and thigh sites was performed in an outside laboratory where it was reported as poorly differentiated neoplasm. We had received review slides from both the sites (chest wall and thigh) for second opinion. Smears from both the sites were highly cellular and showed singly scattered and occasional clusters of variably sized cells, predominantly small with a few intermediate to large atypical cells. The large pleomorphic cells had high nucleo-cytoplasmic ratio, coarse chromatin with two to three conspicuous nucleoli and a moderate amount of cytoplasm. An occasional cell with embryo-like nuclei (cells with lobulated nuclei) and some lymphoglandular bodies (cytoplasmic fragments of lymphoid cells seen in the background), mixed inflammatory infiltrate and haemorrhage were seen in the background (figure 2A,B). As no cell block was available, immunocytochemistry could not be performed. The case was reported as a small round cell tumour. Subsequently, biopsies from both the sites were performed, which showed similar morphology, showing a cellular tumour arranged in a solid, cohesive pattern with traversing thin fibrous septae. These tumour cells were predominantly small-sized cells to few intermediate to large-sized cells. The intermediate-sized cells had irregular nuclear margins, coarse chromatin, conspicuous nucleoli and scant to moderate cytoplasm. Some of the cells had embryoid-like morphology. Few atypical mitosis and apoptotic bodies were seen. A possibility of a small round cell tumour, with an initial consideration of rhabdomyosarcoma and Ewing’s sarcoma, was kept. However, an immunohistochemical panel comprising of desmin, myogenin, MyoD1 and CD99 was negative. Further immunohistochemistry (IHC) panel considering haematopoietic neoplasm (including myeloid sarcoma, Langerhans cell histiocytosis (LCH), histiocytic sarcoma and lymphoma), melanoma and poorly differentiated carcinoma was ordered. However, the tumour cells were negative for Pan-CK, CD21, CD1a, HMB-45, TdT, MPO and CD68, while these cells showed diffuse expression of CD45. Further, panel for lymphoma, including CD3, CD20, CD79a, CD4, CD5, CD8 and CD30, was applied. However, none of these markers, except CD30 and CD4, showed expression in tumour cells. After that, a diagnostic suggestion of ALCL was raised as ALCL is often known to show frequent loss of one or more T cell markers. IHC for ALK showed strong cytoplasmic staining in tumour cells (figure 3A–D). Based on these findings, a diagnosis of ALK-positive ALCL was considered. Fluorescence in-situ hybridisation testing from chest wall biopsy showed chromosomal abnormality t(2;5), corresponding to NPM1-ALK fusion transcripts. Bone marrow was not involved by the lymphoma. Systemic chemotherapy was initiated.