Final Diagnosis -- Histiocytic Neoplasm, Post-acute Lymphoblastic Leukemia



Given the patient's history, the primary diagnostic consideration for the lip soft tissue mass is a pre-cursor B-cell acute lymphoblastic lymphoma. However, the histopathology of the tumor highly favors of a proliferation of histiocytic cells rather than lymphoblasts. On H&E examination, the differential diagnosis also includes sarcomatous tumors, including dendritic cell and Langerhans cell neoplasms. Immunostains support a true histiocytic lymphoma (THL), with an immunophenotype compatible with a phagocytic histocyte origin (i.e. positive for CD68 (PGM1), CD45, CD4, CD163, CD14 and focally positive for lysozyme, with lack of staining for dendritic cell markers (CD23, CD123, CD21) and Langerhans cell markers (S100, CD1a). The tumor immunophenotype was negative for B-cell markers, including CD79a, CD20, PAX-5, and TdT. Thus, the diagnosis of histiocytic neoplasm was rendered. While there is a paucity of case series data to accurately predict survival or response to therapy for THL following ALL, de novo THL will generally demonstrate an aggressive clinical course (Weiss et al., 2001). Additionally, the current lesion shows features that indicate the possibility of a more aggressive clinical behavior, including local recurrence and an elevated Ki-67 proliferative rate.

Several cases of THL in pediatric patients with previous acute lymphoblastic leukemia/lymphoma (ALL) have been reported (Soslow et al, 1996; Bouabdallah et al, 2001; Wongchanchailert and Laosombat, 2003; Feldman et al, 2004). In each of these cases, the THL arose approximately 1-4 years following achievement of complete remission from ALL. The THL was either unifocal (Soslow et al., 1996) or presented with multifocal (Wongchanchailert and Laosombat, 2003; Bouabdallah et al, 2001) or disseminated disease (Feldman et al, 2004). Our case is remarkable for the development of apparently unifocal THL approximately 1.5 years after induction of complete remission of precursor B-cell ALL in an adult male. A recent bone marrow evaluation shows continued remission of the ALL in this patient.

In 2001, Bouabdallah and colleagues reported a case of a 19-H&E 1year-old male who developed THL of the mesenteric lymph nodes 4 years following successful treatment for precursor B-cell ALL. This apparently was the first case to demonstrate a common clonal relationship between the two neoplasms. They employed PCR-based immunoglobulin and T-cell receptor gene rearrangement studies to demonstrate common monoclonal rearrangements in the THL and the previous B-ALL. More recently, Feldman and colleagues (2004) reported identical IgH and TCR- gene rearrangements in a precursor B-cell ALL and a post-treatment histiocytic sarcoma in a 14-year-old male. In our case, we performed FISH testing for the MLL locus to confirm an identical molecular abnormality (Trisomy 11) in the THL and the preceding precursor B-cell ALL. Our result is consistent with these previously reported cases in which there is a common clonal abnormality identified in both neoplasms.

The clonal relationships of these THLs and the predecessor ALLs raise interesting possibilities regarding the origins of these neoplasms and possibly the relationships of corresponding normal cell counterparts. The identification of true histiocytic lesions with common evidence of clonality to a precursor B-cell neoplasm suggests that some lymphocyte precursors may be induced to undergo lineage switch to a histiocytic phenotype. This may be related to host or local tumor environmental factors or possibly to the acquisition of additional, but as yet unidentified genetic alterations.


Bouabdallah R, Abena P, Chetaille B, Aurran-Schleinitz, Sainty D, Dubus P, Arnoulet C, Coso D, Xerri L and Gastaut J-A. (2001). True histiocytic lymphoma following B-acute lymphoblastic leukaemia: case report with evidence for a common clonal origin in both neoplasms. Brit J Haematol. 113: 1047-50.

Feldman AL, Minniti C, Santi M, Downing JR, Raffeld M and Jaffe ES. (2004) Histiocytic sarcoma after acute lymphoblastic leukaemia: a common clonal origin. Lancet Oncol. 5 (4): 248-250.

Soslow RA, Davis RE, Warnke RA, Cleary ML and Kamel OW. (1996). True histiocytic lymphoma following therapy for lymphoblastic neoplasms. Blood. 87 (12): 5207-5212.

Weiss LM, Grogan TM, Muller-Hermelink H-K and Stein H. Histiocytic sarcoma in Pathology and genetics of tumours of haematopoietic and lymphoid tissues. Eds. Jaffe ES, Harris NL, Stein H and Vardiman JW. Lyon: IARC Press; 2001.

Wongchanchailert M and Laosombat V. (2003). True histiocytic lymphoma following acute lymphoblastic lymphoma. Med Pediatr Oncol. 40: 51-53.

Contributed by Edward D. Plowey, MD, PhD and Raymond E. Felgar, MD, PhD

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