|Year : 2013 | Volume
| Issue : 2 | Page : 317-319
Small cell variant of anaplastic large cell lymphoma presenting as arm mass in a child: A rare entity with diagnostic challenge
Sunil Pasricha, Jatin S Gandhi, Gurudutt Gupta, Anurag Mehta
Department of Pathology. Rajiv Gandhi Cancer Institute & Research Centre, Sector 5, Rohini, New Delhi, India
|Date of Web Publication||13-Jun-2013|
Department of Pathology, Rajiv Gandhi Cancer Institute and Research Centre, Sector 5, Rohini, New Delhi-110 085
Source of Support: None, Conflict of Interest: None
Anaplastic lymphoma kinase positive, anaplastic large cell lymphoma (ALCL) is an uncommon T-cell non-Hodgkin lymphoma. A rare morphological variant-small cell variant of ALCL may pose diagnostic challenge especially when it presents primarily as a soft tissue mass. We present a rare case of small cell variant of ALCL in a 14-year-old female presented with arm swelling with emphasis on clinical, morphological and immunohistochemical aspects. Pathologists should be aware of this entity when considering a differential diagnosis of malignant round cell tumor as early and correct diagnosis has important clinical implications.
Keywords: Anaplastic large cell lymphoma, non-Hodgkin lymphoma, small cell variant
|How to cite this article:|
Pasricha S, Gandhi JS, Gupta G, Mehta A. Small cell variant of anaplastic large cell lymphoma presenting as arm mass in a child: A rare entity with diagnostic challenge. J Can Res Ther 2013;9:317-9
|How to cite this URL:|
Pasricha S, Gandhi JS, Gupta G, Mehta A. Small cell variant of anaplastic large cell lymphoma presenting as arm mass in a child: A rare entity with diagnostic challenge. J Can Res Ther [serial online] 2013 [cited 2019 Nov 13];9:317-9. Available from: http://www.cancerjournal.net/text.asp?2013/9/2/317/113410
| > Introduction|| |
Anaplastic lymphoma kinase (ALK) positive, anaplastic large cell lymphoma (ALCL) is an uncommon T-cell non-Hodgkin lymphoma (NHL) and has been a relatively heterogeneous entity with morphological and clinical spectrum. The most common histomorphologic form is of large cells with anaplastic features and hallmark cells with consistent expression of CD30. ,, However, an uncommon but well recognised variant with a small cell pattern may pose a diagnostic challenge especially when it presents primarily as soft tissue mass. Pathologists need to be aware of this entity and its diagnostic importance since it has a better prognosis than other T-cell lymphomas and hence important clinical implications. , We report a rare case of small cell variant (SCV) of ALCL with emphasis on the histomorphological and immunohistochemical aspects of this entity.
| > Case Report|| |
A 14-year-old female with no significant past and family history presented with rapidly growing swelling over the right arm since 15 days associated with on and off fever and restriction of arm movements. Routine haematological and biochemistry investigations were normal. Patient underwent a magnetic resonance imaging study which showed extensive swelling and oedema involving long head of biceps with partial involvement of short head. The joints and humeral shaft were free. The patient also had multiple enlarged right axillary and supraclavicular lymph nodes measuring 16 mm in longest axis. A radiological diagnosis of pyomyositis with reactive lymphadenopathy was offered. Fine needle aspiration cytology (FNAC) was done which was suggestive of a malignant round cell tumor with a morphological possibility of rhabdomyosarcoma (RMS). Subsequently, a trucut biopsy was performed and hematoxylin and eosin (H and E) showed diffuse proliferation of neoplastic cells round to oval, small to medium in size having fine granular chromatin, irregular nuclear outlines and small conspicuous nucleoli with scant to moderate eosinophilic cytoplasm. Occasional cells show convulated nuclei. The tumor was infiltrating the skeletal muscle fibres [Figure 1]. The mitotic activity was significant with areas of tumor necrosis. Overall features were suggestive of a malignant round cell tumor with a morphological possibility of RMS. Immunohistochemistry (IHC) results of primary panel showed positivity for vimentin, CD45 and negativity for cytokeratin (CK), desmin and Myo-D1. The above findings pointed towards a high grade non-Hodgkin lymphoma. A secondary panel was given which showed positivity for CD30, epithelial membrane antigen (EMA), CD2, CD30 with negativity for Terminal deoxynucleotidyl Transferase (TdT), CD20, PAX5, CD5 and CD7. Further ALK-1 showed strong nuclear and cytoplasmic positivity [Figure 2] and hence a final diagnosis of SCV of ALCL was rendered. On reviewing the hematoxylin and eosin slides very occasional small hallmark like cell was evident interspersed in between the small cells. Subsequently positron emission tomography (PET)-computed tomography (CT) scan showed hypermetabolic soft tissue deposit in the right gluteal muscle, left arm, right thigh, left chest wall and perihepatic region besides the dominant lesion in the right arm [Figure 3]a and b. The patient was subjected for chemotherapy (8 cycles) in accordance with APO regimen comprising of doxorubicin, prednisone and vincristine. After 4 th and 8 th cycle of chemotherapy PET-CT was done which showed no metabolic uptake in the body and hence complete response was achieved [Figure 3]c and d. After seven months of follow up patient is doing well and at present is undergoing maintenance therapy for one year comprising of methotrexate and 6-mercaptopurine.
|Figure 1: Microphotograph showing (a) diffuse proliferation of small round tumor cells infiltrating the skeletal muscle (H and E, ×100); (b) small round tumor cells small with scanty to moderate eosinophilic cytoplasm (H and E, ×400)|
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|Figure 2: (a-d) microphotograph showing immunopositivity of tumor cells for CD45, CD30, CD3 and ALK-1 (IHC, ×200)|
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|Figure 3: (a and b) Pre-chemotherapy PET-CT scan showing hypermetabolic dominant lesion in the right arm; (c and d) PET-CT scan after 4th cycle of chemotherapy showing complete response with regression of the lesions|
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| > Discussion|| |
ALK positive ALCL occurs most frequently in the first three decades of life with male predominance. This lymphoma involves both nodal as well as extranodal sites frequently. The most commonly involved extranodal sites are the skin, bone, soft tissue, lung and liver. Most of the patients present with constitutional symptoms often with stage III or IV at initial diagnosis. The incidence of bone marrow involvement is approximately 10-11% when analysed with routine H and E stains and this detection rate increases to 30% when ancillary IHC studies are used. ,, SCV of ALCL presents almost similar to the other ALK positive ALCL neoplasm with the exception that leukemic involvement has been more commonly described in small cell variant. ,
In the discussed case patient presented with mass in the right arm. The differential diagnosis of childhood neoplasm with similar clinical presentation comprises of RMS, Ewing sarcoma/PNET and uncommonly hematolymphoid malignancy which includes lymphoblastic lymphoma, ALCL, myeloid sarcoma and other high grade NHL. H and E stained slides revealed diffuse proliferation of small to medium sized cells with very occasional cell having convoluted nuclei. IHC positivity for CD45 and negativity for desmin, Myo-D1 and CD99 ruled out the differential diagnosis like RMS and Ewing sarcoma pointing towards a hematolymphoid malignancy. Further positivity for CD2, CD3, C30, EMA and ALK-1 protein with negativity for TdT, CD20, PAX5, CD117 and CD99 led to the final diagnosis of small cell variant of ALK positive ALCL and excluded the other hematolymphoid neoplasm differentials. Bone marrow was morphologically uninvolved and was confirmed with IHC.
Recent study by Sung et al. had revealed unexpectedly high expression (70%) of CD99 in ALK-positive ALCL compared to 20% positivity in ALK-Negative ALCL, but negativity in other mature T/NK cell neoplasms. Hence, the role of ALK-1 is highly important to distinguish the SCV of ALCL from Ewing's sarcoma/Primitive neuroectodermal tumor (PNET).  Moreover IHC panel must include TdT, as lymphoblastic lymphoma presenting as soft tissue mass is CD99 positive and can be LCA negative which can lead to erroneous diagnosis of Ewing's sarcoma/PNET if CD99 positivity is considered along with LCA negativity. 
The biological behaviour of SCV of ALCL has been a matter of debate. Hodges et al. reviewed 17 cases of SCV of ALCL out of which 4 cases (24%) transformed to classical ALCL. The transformation to classical ALCL signalled rapid clinical course with 3 cases (75%) dying in less than a year. Clinically, the SCV of ALCL is a biologically aggressive lymphoma with an overall 2-year survival of 50% compared with 73% in classical ALCL.  Whether this is related to the disseminated nature of the tumor in many patients or to truly more aggressive tumor biology is not well understood. 
Few authors believe that different histologic variants do not appear to have distinct prognostic significance and should not be considered as "histologic grades" or "prognostic variants". These histologic variants are part of single clinicopathological entity and can be seen in the same patients at different points in time. Cytogenetic studies show t(2;5) and most recently nucleophosmin (NPM)-ALK fusion protein in the small and large cells of SCV have strongly supported this concept. ,,
In conclusion SCV of ALCL is rare entity which is difficult to recognise and poses a diagnostic challenge. Pathologists should be aware of this entity when considering a differential diagnosis of malignant round cell tumor in any young patient presenting with soft tissue mass and constitutional symptoms with or without lymphadenopathy. Early and correct diagnosis has important clinical implications and has better prognosis than other types of T-cell NHL.
| > Acknowledgement|| |
Dr. Anila Sharma, Consultant, Department of Pathology, Rajiv Gandhi Cancer Institute and Research Centre, Sector 5, Rohini, New Delhi-110085, India.
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[Figure 1], [Figure 2], [Figure 3]