Indian Journal of Pathology and Microbiology

: 2018  |  Volume : 61  |  Issue : 2  |  Page : 278--280

Extranodal histiocytic sarcoma in a child with acute lymphoblastic leukemia: Cytomorphological features of a rare entity with brief review of literature

Krushna Chandra Pani1, Mahima Yadav1, Shaleen Kumar2, Vinita Agrawal1,  
1 Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
2 Department of Radiotherapy, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Correspondence Address:
Vinita Agrawal
Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow - 226 014, Uttar Pradesh


Histiocytic sarcoma (HS) is a rare malignant neoplasm showing morphologic and immunophenotypic evidence of histiocytic differentiation. We describe a rare case of synchronous HS in a patient of B-cell acute lymphoblastic leukemia (ALL). A 16-year-old boy diagnosed as ALL also presented with a swelling over the right Achilles tendon. The cytological features of the swelling suggested a histiocytic lesion. Histological and immunohistochemical examination clinched the diagnosis of HS. The available 5-year follow-up showed no recurrence. It was a diagnostic dilemma on fine-needle aspiration. We discuss the cytological features of HS which can help in reaching a diagnosis and emphasize that it should be considered in the differential diagnosis for unexplained swellings in patients of hematological malignancies. Wide local excision of localized HS is associated with a long-term favorable outcome.

How to cite this article:
Pani KC, Yadav M, Kumar S, Agrawal V. Extranodal histiocytic sarcoma in a child with acute lymphoblastic leukemia: Cytomorphological features of a rare entity with brief review of literature.Indian J Pathol Microbiol 2018;61:278-280

How to cite this URL:
Pani KC, Yadav M, Kumar S, Agrawal V. Extranodal histiocytic sarcoma in a child with acute lymphoblastic leukemia: Cytomorphological features of a rare entity with brief review of literature. Indian J Pathol Microbiol [serial online] 2018 [cited 2020 Oct 25 ];61:278-280
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Histiocytic sarcoma (HS) is a rare malignant neoplasm showing morphologic and immunophenotypic evidence of histiocytic differentiation.[1] It is defined in the WHO classification as a neoplastic proliferation with features of histiocytes. Extramedullary myeloid tumors with monocytic differentiation and dendritic cell neoplasms are excluded from the study. HS can be sporadic or may be clonally related to a hematologic malignancy, usually follicular lymphoma, or acute lymphoblastic leukemia (ALL).[1],[2] Cytological diagnosis is difficult unless a possibility of HS is considered in the differential diagnosis. We describe the pathological features of a rare case of HS involving the right Achilles tendon in a patient of ALL.

 Case Report

A 16-year-old boy presented with episodes of low-grade fever, diarrhea, and weight loss for 1 month. Physical examination revealed generalized lymphadenopathy and a small nodular painless swelling on the right Achilles tendon. Peripheral smear, bone marrow examination, and immunophenotyping were done, and the patient was diagnosed as B-cell ALL. Myeloperoxidase cytochemistry and immunophenotyping for myeloid markers were negative. He was put on standard risk BFM-90 protocol. Complete remission was achieved. The swelling over the Achilles tendon persisted. Further evaluation of the swelling was not performed, and the patient was on routine follow-up.

Five years later, the patient complained of increase in size of the right Achilles tendon swelling. Local examination revealed an ulceroproliferative growth measuring 5 × 4 × 4 which was fixed to the tendon. Computed tomography scan showed no involvement of the underlying bone. Fine-needle aspiration cytology (FNAC) and subsequent wide local excision of the growth with flap reconstruction were done at the local site. There was no evidence of recurrence of ALL on peripheral smear and bone marrow examination.

The FNAC smears were cellular and showed a dispersed population of large-to-medium-sized cells along with a mixed inflammatory cell infiltrate. The cells had round-to-oval eccentric nuclei, vesicular chromatin, 1–2 conspicuous nucleoli, and abundant pale to finely vacuolated cytoplasm. Few binucleate and multinucleate histiocytic cells along with some showing cytoplasmic debris and erythrophagocytosis were also seen [Figure 1]. Possibility of a histiocytic lesion was kept, and histopathology was advised for confirmation.{Figure 1}

Histology of the excised lesion showed sheets of polymorphic medium-to-large-sized cells with round-to-irregular vesicular nuclei and abundant eosinophilic cytoplasm along with interspersed mature lymphocytes, plasma cells, and occasional eosinophils. No nuclear grooving was seen. Focal spindling of the tumor cells, few multinucleated giant cells, hemophagocytic activity, and few mitotic figures were also seen [Figure 2]. On immunohistochemistry, the tumor cells showed expression of CD68, CD45, vimentin, and S-100 and were negative for CD1a, cytokeratin, CD30, CD10, CD117, CD34, HMB-45, and myogenin [Figure 3]. A diagnosis of HS involving the Achilles tendon was thus offered. The patient was on follow-up.{Figure 2}{Figure 3}

Five years later, the patient was diagnosed to have multiple space-occupying lesions in the right lobe of the liver. Ultrasound-guided FNAC, biopsy, and immunohistochemistry of liver lesions were performed. The results were consistent with leukemic infiltrate, rather than a histiocytic lesion (leukocyte common antigen, CD99 positive). Peripheral blood and bone examination done showed no relapse of leukemia. The patient was again started on high-dose chemotherapy and he responded very well to chemotherapy. The lesion on the Achilles tendon did not recur. However, 6 months later, the patient died of pancytopenia and severe sepsis.


HS is a hematopoietic neoplasm with morphological and immunohistochemical features of mature tissue histiocytes. It was described previously as “true histiocytic lymphoma” or as “malignant histiocytoses;” both of the terms are no longer used.[1] HS has been reported in association with malignant neoplasms, including a number of hematological malignancies.[1],[3] The other histiocytic lesions described in ALL are juvenile xanthogranulomas, Langerhans cell histiocytosis, Langerhans cell sarcoma, and Rosai–Dorfman disease.[4]

The risk factors for HS are unknown. Several earlier studies have reported histiocytic lesions in association with ALL. Soslow et al. described three cases of true HS in association with ALL.[5] There are studies which have performed molecular or cytogenetic analysis to establish the clonality between concurrent lymphoid and histiocytic neoplasms.[4],[6] These findings suggest the possibility of transdifferentiation of the two neoplasms which are morphologically and immunophenotypically distinct.[7] In our patient, the primary diagnostic consideration for the Achilles tendon mass was leukemic deposit. However, the cytological, histopathological, and immunohistochemical features of neoplastic cells were not compatible with that of lymphoblasts and favored a histiocytic proliferation.

HS can present as a solitary mass involving single organ or can present as a systemic disease. It can be nodal or extranodal. Gastrointestinal tract, soft tissue, and skin are the most common sites of extranodal involvement; however, uncommon sites such as salivary glands, breasts, lungs, pancreas, kidney, uterus, and central nervous system can be involved.[1],[2],[7],[8]

Studies on the cytological features of HS are sparse. Few earlier case reports have reported similar cytological features in HS as found in our patient.[9],[10] The cytological features described include medium-to-large cells with central-to-eccentric pleomorphic nuclei, vesicular chromatin, prominent nucleoli, and abundant pale to vacuolated cytoplasm associated with a prominent inflammatory cell infiltrate.[9],[10] The histopathological findings of HS are well documented and include diffuse noncohesive proliferation of round-to-oval large atypical cells with abundant eosinophilic cytoplasm. The tumor cells usually have oval-to-irregular nuclei with vesicular chromatin and prominent eosinophilic nucleoli. Binucleate or multinucleate forms are commonly seen. Variable mitotic activity, necrosis, and hemophagocytosis may be seen. Some tumors may contain a prominent stromal inflammatory infiltrate.[1],[2] By definition, expression of one or more histiocytic markers including CD68, lysozyme, CD163, or CD11c is necessary for diagnosis of HS. The tumor cells do not express B-cell, T-cell, or myeloid markers. Dendritic cell, epithelial, and melanocytic neoplasm markers should also be excluded from the study.[1],[2] Consistent cytological, histological, and immunohistochemical features were observed in our case.

Traditionally, HS is considered as an aggressive neoplasm and is associated with poor prognosis. A subset of patients who present with clinically localized disease treated with surgery alone has a favorable long-term outcome. Recurrence after wide excision can occur, especially in larger tumors.[1],[3],[8] Our patient had localized HS at presentation with no recurrence for a follow-up of 11 years till the patient died of sepsis.


HS, though uncommon, can be associated with ALL. It should be considered in differential diagnosis of unexplained swellings in patients of hematological malignancies. FNAC is an important first-line diagnostic tool for suspecting the diagnosis and for guiding further management. Wide local excision of localized HS can be associated with recurrence-free long-term favorable outcome.

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Conflicts of interest

There are no conflicts of interest.


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