Anaplastic large cell lymphoma masquerading as rhabdomyosarcoma in fine needle aspiration cytology.

Sir,

Anaplastic large cell lymphoma (ALCL) accounts for approximately 10-20% of the childhood lymphomas.[1] ALCL is a distinct category of large cell lymphomas that shows strong expression of CD30. The reproducibility of ALCL on the morphological ground is poor and at times it may mimic other nonlymphoid malignancies.[2] Herein, we present one such case of ALCL that mimicked rhabdomyosarcoma (RMS) in a child on fine needle aspiration cytology (FNAC).

An 11-year-old boy presented with respiratory distress, chest wall swelling on the left side, cough and inguinal swelling. The left inguinal swelling was 5 cm diameter and mimicked as soft tissue mass on clinical examination. On radiologic evaluation, there was an infiltrative lesion measuring 4 cm × 4 cm in the mediastinum extending into the chest wall.

Fine needle aspiration cytology was done on the chest wall swelling and the left inguinal swelling. Both May-Grόnwald Giemsa (MGG) and hematoxylin and eosin stains were done. The FNAC smears were highly cellular. The cells were arranged around capillaries and singly scattered [Figure 1a]. The tumor cells had abundant cytoplasm with eccentric nuclei, coarse chromatin and prominent nucleoli [Figure 1b]. Numerous bi-nucleated tumor cells and mitotic figures were also noted. Background showed lymphocytes, plasma cells, and red cells. The smears from the inguinal lesion also showed tumor cells of similar morphology. Hence considering the age, site and morphology a diagnosis of malignant round cell tumor, possibly RMS was suggested. The patient was put on chemotherapy, and the mediastinal mass persisted. Hence, a biopsy was done from the chest mass which showed cells of similar morphology with muscle infiltration and areas of necrosis [Figure 1c]. On immunohistochemistry, the cells were positive for CD45 [Figure 1d] but negative for CD3, CD20 and desmin. A diagnosis of lymphoma was suggested. A bigger biopsy was planned from the inguinal node, and panel of antibodies was used. The tumor cells were strongly positive for leukocyte common antigen, CD30 [Figure 1e] and anaplastic lymphoma kinase (ALK)-1 [Figure 1f] and negative for CD3, CD20 and desmin.

Figure 1

(a) Smear shows pericapillary arrangement of cells, (MGG, ×220). (b) Discrete cells with frequent bi-nucleation and multi nucleation, (MGG, ×220). (c) Histopathology section from the chest wall mass showing infiltration of tumor cells within the muscle, (H and E, ×220). (d) CD45 positivity of the tumor cells, (IHC, ×220). (e) CD30 positivity of the tumor cells, (IHC, ×220). (f) Anaplastic large cell lymphoma: Strong anaplastic lymphoma kinase positive cells (IHC, ×220)

Finally, the diagnosis of ALCL was given.

Anaplastic large cell lymphoma accounts for approximately 10-20% of the childhood lymphomas. This is the most common tumor in the first three decades of life with mildly higher incidence in males.[1] It involves the lymph nodes and extranodal sites like skin, bone, soft tissue, lung, and liver. Mediastinal disease is less frequent. ALCL represents a distinct category of large cell lymphomas defined by a strong expression of CD30 on all or most of the neoplastic cells and a so-called anaplastic cytology, usually associated with a characteristic growth pattern of the tumor cells such as sinusoidal dissemination, and perifollicular or perivascular homing.[3] The detection of CD30 (in conjunction with other lymphoid and non-lymphoid markers) is also important, not only in the differential diagnosis between ALCL and non-lymphoid anaplastic large cell tumors, but also to distinguish between ALCL and other types of lymphomas. It has recently been shown that the reproducibility of the diagnosis of ALCL on morphologic grounds is 46%, but it can be increased to 85% by immunostaining for CD30.[3]

The differential diagnoses of ALCL are Hodgkin lymphoma (HL), anaplastic carcinoma, and sarcoma. ALCL cases are often confused with sarcoma on FNAC smears. Rapkiewicz et al.[2] reviewed 37 patients with ALCL and out of which only 13 cases were diagnosed initially as ALCL on FNAC. They noted variable degree of cellular pleomorphism on the FNAC smears. The characteristic hallmark cells were found in only 11 cases. Lymphoglandular bodies were absent in non-lymph node specimens.

Poorly differentiated carcinoma also shows many discrete large pleomorphic cells and may be confused with ALCL. However, the absence of lymphoglandular bodies and the hallmark cell may eliminate the possibility of ALCL. The strong presence of cytokeratin and epithelial membrane antigen in the tumor cells indicate the diagnosis of carcinoma over ALCL.

Hodgkin lymphoma often shows large pleomorphic popcorn like cells and bi-nucleated Reed-Sternberg cells. The FNAC smear of HL may simulate ALCL. Immunocytochemistry of the tumor cells show both CD15 and CD30 positivity and ALK negativity in HL.

Similarly, round cell sarcomas such as RMSs may often come in the differential diagnosis of ALCL. This is due to the presence of round to oval cells in the smears of RMS cases. The presence of strap cells may help in such cases for establishing the diagnosis of RMS. In this index case we misdiagnosed the case as RMS because of discrete cells with abundant cytoplasm and eccentric nuclei. There was almost absence of lymphoglandular bodies. We did not make cell block in this particular case. Detailed immunocytochemistry would have helped.

Diagnosing ALCL on FNAC cytology is difficult because of the wide spectrum of cytomorphologic findings but it may be successfully done with the aid of ancillary tests, such as immunocytochemistry and flow cytometry (FCM). It is important for cytopathologists to consider ALCL in the differential diagnosis of lesions characterized predominantly by discohesive, pleomorphic cells. It is, therefore, essential to obtain adequate material for ancillary testing at the time of the procedure. This can be either in the form of additional passes for FCM and/or cell block from FNAC samples. This is really important because the exact categorization and treatment protocol will definitely affect the prognosis of the patient.