|Year : 2015 | Volume
| Issue : 3 | Page : 658
Coexistence of tuberculosis with histiocytic sarcoma: A rare association
Riti Aggarwal, Seema Rao
Department of Pathology, Sir Ganga Ram Hospital, New Delhi, India
|Date of Web Publication||9-Oct-2015|
Department of Pathology, Sir Ganga Ram Hospital, New Delhi - 110 060
Source of Support: None, Conflict of Interest: None
Histiocytic sarcoma (HS) is an exceedingly rare hematolymphoid neoplasm of histiocytic lineage. We report a case of 25-year-old Woman who presented with generalized lymphadenopathy and ascites. There was no personal or family history of tuberculosis (TB). Histopathological examination of omental and peritoneal biopsy revealed TB while mesenteric lymph node showed HS. This case highlights the fact that a patient may be harboring coexistent malignancy/lymphoma along with TB. Therefore, the clinician should have a high index of suspicion, especially when there is therapeutic failure to antitubercular drugs (ATT) and persistence of fever or generalized lymphadenopathy. Sometimes, there may be surprising presence of uncommon malignancies, like in our case, where we found HS with TB. Since both diseases share similar clinical and radiological features, it is highly possible that one may not look further, once one of these is diagnosed.
Keywords: Generalized lymphadenopathy, histiocytic sarcoma, tuberculosis
|How to cite this article:|
Aggarwal R, Rao S. Coexistence of tuberculosis with histiocytic sarcoma: A rare association. J Can Res Ther 2015;11:658
| > Introduction|| |
Histiocytic sarcoma (HS) is an uncommon hematolymphoid neoplasm, with morphologic and immunophenotypic features of mature histiocytes. Due to poorly differentiated morphology and the difficulties in characterizing their histiocytic derivation, these tumors are under-recognized. In the present case, we describe a rare coexistence of HS in mesenteric lymph node with tuberculous deposits in omentum and peritoneum.
| > Case report|| |
A 25-year-old woman presented with the complaints of breathlessness, abdominal distension, generalized weakness and weight loss. The patient had no past or family history of tuberculosis (TB). Physical examination revealed generalized lymphadenopathy and ascites. Contrast-enhanced computed tomography (CECT) done outside showed multiple enlarge para-aortic, superior mesenteric and parapancreatic lymph nodes and miliary deposits over parietal peritoneum without pulmonary infiltrates. All the visceral organs including genitourinary system were normal. Clinical and radiological findings were suggestive of TB or lymphoma. Omental, peritoneal nodule, and mesenteric lymph node biopsy was done.
Histopathological examination of omental and peritoneal biopsy revealed ill-defined granulomas with minimal caseation. Ziehl-Neelsen stain for acid-fast bacilli showed occasional bacilli, thus confirming tuberculous nature of omental and peritoneal deposits. Mesenteric lymph node measured 1.2 × 1 cm and showed partial effacement of architecture by sheets of atypical cells which were irregular, oval to reniform, having vesicular nuclei with 1-2 prominent eosinophilic nucleoli. Some of the nuclei had nuclear indentation and folding. Cytoplasm was finely granular and eosinophilc. Morphology suggested high grade poorly differentiated malignant tumor [Figure 1]a. To assign a definite lineage to the tumor, a broad panel of immunohistochemical (IHC) markers was done. Tumor cells were diffusely positive for CD68 [Figure 1]b, weakly positive for leukocyte common antigen (LCA) [Figure 1]c, vimentin [Figure 1]d and S-100, suggesting a histiocytic lineage. Fascin was positive [Figure 2]a. Focal dot-like positivity for cytokeratin was also seen. However, CD21 was completely negative [Figure 2]b. Cells were negative for CD3, CD20, CD30, CD15, Alk-1, myeloperoxidase and HMB-45 thereby excluding T-cell/B-cell lymphoma, Hodgkin disease, anaplastic large cell lymphoma, granulocytic sarcoma, and malignant melanoma, respectively. CD1a negativity ruled out Langerhans cell histiocytosis. Manufacturer and clone information of positive (IHC) markers is provided in [Table 1].
|Figure 1: (a) Photomicrograph showing sheets of atypical cells which were irregular, oval to reniform, having vesicular nuclei, prominent eosinophilic nucleoli and finely granular and eosinophilc cytoplasm (H and E, ×400). (b) diffuse and strong positivity of tumor cells for CD68. (c) weak positivity for leukocyte common antigen, and (d) vimentin|
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|Figure 2: (a) Tumor cells are positive for fascin and (b) negative for CD21|
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Hence, the final diagnosis of HS, mesenteric lymph node coexistent with tuberculous deposits in the peritoneum and omentum, was given and the patient was put on ATT and chemotherapy.
Post one cycle of chemotherapy, patient presented in the emergency department for severe dyspnea and abdominal distension and her whole body positron emission tomography-CECT scan revealed fluorodeoxyglucose avid supraclavicular, mediastinal, para-aortic, abdominal and retroperitoneal lymphadenopathy; omental, peritoneal, and mesenteric thickening [Figure 3]. Patient was put on mechanical ventilation, but within 15 days of treatment, she died due to fatal respiratory arrest.
|Figure 3: Positron emission tomography contrast-enhanced computed tomography scan revealing fluorodeoxyglucose avid supraclavicular, mediastinal, para-aortic, and abdominal lymphadenopathy|
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| > Discussion|| |
Histiocytic sarcoma is characterized by neoplastic proliferation of cells showing histiocytic differentiation.  Its diagnosis requires the concordance of clinical, morphological and immunophenotypic features and the exclusion of other hematopoietic and nonhematopoietic mimics. HS occurs most commonly in adults. Infants and children may also be affected. Most common site of presentation is lymph nodes, although extranodal sites such as skin, gastrointestinal tract, spleen, central nervous system, soft-tissues, and lungs may also be affected. Some cases of HS occur subsequent to or concurrent with B-or T-cell lymphomas.  The association of HS with a primary gonadal/mediastinal germ cell tumor has also been described.  In the present case, the patient had generalized lymphadenopathy. While, omental and peritoneal biopsies showed tuberculous deposits, mesenteric lymph node was reported as HS.
There is no single immunophenotypic marker diagnostic of HS. A wide panel is necessary to make a definite diagnosis and exclude the possible differential diagnoses.  CD68, lysozyme, CD11C, and CD14 help to determine histiocytic phenotype while LCA, CD45RO, and CD4 confirm the hematolymphoid nature of HS. In general, HS is negative for B-cell, T-cell, and Alk-1; and also do not express markers of other morphological mimics such as Langerhans cell histiocytosis, leukemia deposit, metastatic carcinoma, or melanoma.
It is also important to differentiate HS from follicular dendritic cell tumor (FDCT) and interdigitating dendritic cell tumor (IDCT). In the present case, although fascin was positive, but negativity of tumor cells for CD21 and strong positivity for CD68 ruled out FDCT. Exact role of fascin in HS diagnosis has not been much described in the literature. Since fascin alone may be misleading for diagnosis, as in our case, a more definite FDC marker (CD21) should be used in conjuncture, to distinguish HS from FDCT. HS may also be morphologically confused with IDCT as both neoplasms have S-100 and CD68 positivity. Features like long dendritic cell processes, convulated nuclei, diffuse and stronger staining for S-100 and variable and often weaker staining for CD68 favor the diagnosis of IDCT.
Existing data of HS suggest that most of the cases present at a clinically advanced stage, follow an aggressive clinical course and have limited response to chemotherapy.  Only, a subset of cases presenting as clinically localized disease may have a favorable long-term outcome.
Tuberculosis is the most common infectious disease in the developing country, commonly affecting lungs. In the present case, patient presented with generalized lymphadenopathy and miliary deposits, and was found to have both TB and HS. This case highlights that sometimes, a patient may be harboring two different diseases. Not infrequently, in such case, diagnosis of one may delay detection of the other. Therefore, the close association and coexistence of the two must be recognized for the proper diagnosis and treatment of the patient. Literature has mentioned the association or coexistence of TB with Hodgkins and non-Hodgkins lymphoma (NHL). , However, no case report describing a coexistence of TB and HS has been published so far to the best of our knowledge.
Various hypotheses have been postulated for association of TB and lymphoma. TB is a chronic infectious disease whose presentation and reactivation is promoted by cell-mediated immunodeficiency, which is present in cases of lymphoma. Furthermore, the introduction of immunosuppressive drugs for lymphoma may worsen the clinical course of TB. Likewise, lymphomas are also related to immune deficiency and may be preceded by infectious diseases. Mycobacterial infection may escape the host's cellular response and establish an appropriate microenvironment for tumorigenesis by causing direct DNA damage, inhibiting apoptosis, perpetuating chronic inflammation coupled with enhanced angiogenesis.  However, in a case with simultaneous detection of both entities like ours, it may not be possible to comment on the cause and effect status.
| > Conclusion|| |
Since TB can coexist with hematolymphoid malignancies and have overlapping clinical presentation, the clinician should suspect coexisting pathology, in addition to multi-drug resistant TB, if a patient has persistent nodes post-AKT or vice versa. Therefore, a detailed clinical workup in conjunction with histological and microbiologic evaluation should be pursued to decrease the possibility of a diagnostic pitfall and a therapeutic mishap.
Association of TB with Hodgkins and NHL is well-known. Hereby, we describe the first case of coexistence of TB and HS emphasizing the fact that a patient may be harboring coexistent malignancy/lymphoma, sometimes rare ones like HS along with TB. Furthermore, fascin positivity is insufficient in itself to differentiate HS from FDCT as highlighted by this case. Therefore, thorough histological evaluation and a comprehensive IHC panel including S-100, CD68 fascin as well as CD21 may be required for the same.
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[Figure 1], [Figure 2], [Figure 3]