Extra Pulmonary Tuberculosis as an initial presentation in Acute Myeloid

Leukemia: A rare entity

Dr Shahzad Sarwar Resident Oncology department Aga Khan

University Hospital Karachi. shahzadsajjad99@gmail.com
Dr M Sajjad Sarwar Resident Pulmonology department Aga Khan
University Hospital Karachi. sajjadshahzad99@gmail.com
Dr Salman Naseem Adil Professor Hematology /Pathology Department
Aga Khan University Hospital Karachi. salman.adil@aku.edu
ABSTRACT

Presenting with respiratory symptoms is frequent in acute myeloid leukemia

patients and the cause is multifactorial. Infectious etiology is the commonest, but
among them extra pulmonary tuberculosis with wide mediastinum is extremely
rare. Tuberculosis is rarely the initial presentation of AML.It can occur during the
course of chemotherapy and post stem cell transplant. Here we describe a case of
45 year old male presented with wide mediastinum and high WBC count. Biopsy
of mediastinal nodal mass revealed tuberculosis while bone marrow aspiration and
flow cytometry were consistent with AML M2. Successfully treated with anti
tuberculosis therapy for 6 months and chemotherapy followed by allogenic stem
cell transplant for AML.
INTRODUCTION

Tuberculosis can occur in hematological malignancies, results in significant

mortality and morbidity. In acute myeloid leukemia it usually presents during the
course of chemotherapy or after allogenic stem cell transplant (1). Persistent fever
with pan culture negative while acute leukemia in remission is the common
scenario noted. Initial presentation with mediastinal lymphadenopathy causing
wide mediastinum is very rare.

Lymphadenopathy is a feature of acute lymphoblastic leukemia (ALL) but rare in

AML. Leukemic infiltration (especially in AML M4, AML M5 variants),
tuberculosis and lymphoma are among the strongest differential in a patient of
acute myeloid leukemia presenting with wide mediastinum due to
lymphadenopathy(2). Definite diagnosis requires biopsy of lymph node. Biopsy
can be challenging in presence of low platelet count and bleeding diathesis.
Presence of necrotic lymph nodes on CT scan support tuberculous
lymphadenopathy instead of lymphoma.

Treatment with anti tuberculous therapy for 6-9 months is the standard treatment
modality. Response is monitored with disappearance of the clinical symptoms and
resolution of the lymphadenopathy. The anti tuberculous therapy should be started
concomitantly with the chemotherapy.
CASE REPORT

A 45 year old male presented with 6 week history of fever, dry cough and weight
loss . The symptoms began with low grade intermittent fever and dry cough that
was associated with anorexia and unquantified weight loss. He had no history of
contact with tuberculous patient. On examination he looked pale while systemic
examination was unremarkable.

Blood counts revealed hemoglobin 7.6 mg/dl, WBC 146 x 109 /L and platelets were
11 x 109 /L. Peripheral blood smear showed 78% blast cells and thrombocytopenia.
On biochemical analysis glucose 108 mg/dl, Urea 15mg/dl, creatinine 1.2 mg/dl,
LDH 2901I.U/L. Bone marrow aspiration and flow cytometry were consistent with
acute myeloid leukemia with maturation to WHO classification. Conventional
bone marrow cytogenetic showed normal karyotyping and PCR for FLT 3 ITD &
NPM-1 were not detected.

Posterioanterior view chest x ray showed well defined suprahilar paratracheal mass
causing wide mediastinum. CT scan chest with i.v contrast showed generalized
lymphadenopathy with large conglomerate lymph nodal mass in the right para
tracheal region 9.5 x 8 cm in size.

CT guided biopsy of mediatinal lymph node was done which showed effacement
of lymph node architecture by extensive necrosis and multiple well-formed
granulomas composed of epitheloid histocytes and multinucleated giant cells
necrosis consistent with tuberculosis.

Patient was started on four drug regime for pulmonary tuberculosis that included
isoniazid, rifampicin, pyrazinamide and ethambutol (intensive phase of treatment)
followed by a continuation phase of 4 months with isoniazid and rifampicin.
Patients responded well and complete resolution of symptoms and
lymphadenopathy occurred after few weeks (Figure 1 &2). Anti-tuberculosis
therapy stopped after 6 months. No therapy related complication observed during
the course of treatment.

He received induction with standard chemotherapy with daunorubicin and

cytarabine (3+7 protocol). Day 28 bone marrow showed complete remission.
Consolidation was done with high dose cytosar x 3 cycles followed by allogenic
stem cell transplant.

DISCUSSION

Tuberculosis is a serious and can be life-threatening in patient with hematological

malignancies. It predominantly affects males as compare to females. Mishra et al
found that relative risk of developing tuberculosis in acute leukemia is 23 as
compare to general population(3). Chen et al also found that patients with acute
myeloid leukemia had a significantly higher incidence of TB disease then other
subtypes of hematological malignancies (2.87% vs 1.21% p=0.002)(4).

Tuberculosis can occur during the course of disease of after post stem cell
transplant. Febrile illness with the primary disease in remission is usually noted
(5). In the setting of AML presentation with wide mediastinum is rarely noted.
Biopsy of lymph node is necessary to diagnose and differentiate from the AML
infiltration, tuberculosis and lymphoma. Biopsy can be challenging in the presence
of low platelet count and bleeding diathesis. CT appearance of tuberculous
lymphadenitis is variable depending on the degree of caseous necrosis. Initially
enlarged lymphnodes attenuate similar to muscles and eventually central caseation
develops causing central low density (6-7).

Anti TB drugs should be started promptly along with standard induction

chemotherapy protocol. Usually 6 months duration is adequate for treatment of
tuberculous lymphadenitis (8). These drugs have several side effects which
commonly include elevation of liver enzymes, agranulocytosis, nausea,
hyperurecemia (9-10). A successful outcome noted in up to 90% of individuals.
Sometime empiric anti TB drugs is needed if clinical and radiological findings are
strongly suggestive of TB infection especially in endemic areas (11).

In AML most of the patients responded well to anti TB drugs but fatal results can
be there if not diagnosed and treated promptly. Regular follow up should be carried
out for reactivation. In our patient, he remained well for 9 month follow up.
Prompt diagnosis and treatment is required because delay in treatment or treating
leukemia only can lead to fetal dissemination of tuberculosis especially in
immunocompromised patients.

CONCLUSION

AML patient rarely present with wide mediastinum due to lymphadenopathy.

Biopsy should be considered to for definite diagnosis rather then presuming AML
infiltration especially in areas where tuberculosis is endemic.
Figure 1: PA erect view showing well defined suprahilar mass.

Figure 2 : PA erect view post anti TB treatment showed

complete resolution of mediastinal mass.

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