Simultaneous Diagnosis of Myeloid Sarcoma of the Jaw and <i>Mycobacterium tuberculosis</i> Infection

doi:10.4236/jct.2013.46118

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Journal of Cancer Therapy, 2013, 4, 1049-1051

http://dx.doi.org/10.4236/jct.2013.46118 Published Online August 2013 (http://www.scirp.org/journal/jct) 1049

Simultaneous Diagnosis of Myeloid Sarcoma of the Jaw

and Mycobacterium tuberculosis Infection

Luís Arthur Flores Pelloso1,2, Sandra Serson Rohr1, Mihoko Yamamoto1,

Maria de Lourdes L. F. Chauffaille1

1Section of Hematology and Blood Transfusion, Department of Clinical and Experimental Oncology, Federal University of São

Paulo (UNIFESP-EPM), São Paulo, Brazil; 2PPD, Pharmaceutical Product Development, Inc., Pharmacovigilance, São Paulo, Brazil.

Email: [email protected]

Received May 15th, 2013; revised June 17th, 2013; accepted June 24th, 2013

tion License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly

cited.

ABSTRACT

Granulocytic or myeloid sarcoma (MS) is a rare neoplastic condition consisting of a tumor mass of myeloid blasts with

or without maturation occurring at an anatomical site other than the bone marrow the association between tuberculosis

and MS is extremely rare. A 21-year-old female patient presented cough, sore throat and a suppurative swollen gum for

10 days prior to hospital admissio n. Physical examination revealed moderate pallor and swollen inferior gum. CBC re-

vealed Hb 6.5 g/dL, hematocrit 18.4% MCV 97 fL MCH 34 pg, WBC 18.5  109/µL (1 My/3 Bt/69 Sg/1 Eo/0 Ba/20

Ly/6 Mo), Platelets 43  109/µL. The peripheral blood smear presented with 3% blast cells (type 1) and granulocytic

dysplasia. Bone marrow biopsy show ed 100% cellularity. 50% of cells were fr om granulocytic precursors, d iagnosis of

granulocytic sarcoma. The diagnosis of AML was established: granulocytic sarcoma with massive gum infiltration

(immature granulocytic cells) and 10% of blasts in bone marrow. The patient received induction chemotherapy (3 + 7

daunorubicin 90 mg/m2), and gum tissue culture was positive for Mycobacterium tuberculosis. Simultaneously, a qRT-

PCR test confirmed the same bacteria in the gum tissue. Patient treated with isoniazid, rifampicin, pyrazinamide and

ethambutol ciprofloxacin and amikacin). Remission was achieved and the patient was submitted for consolidation/ in-

tensification (HiDAC x3) schema and referred to allogeneic HSCT. After induction and full hematological recovery

there was no further evidence or recurrence of fever and lytic lesions. Currently patient is under CR and ling follow up

(48 mont hs) did not show recurrence of eit her AML or tuberculosi s .

Keywords: Myeloid Sarcoma; Mycobacterium tuberculosis; Granulocytic Sarcoma

1. Introduction

Granulocytic or myeloid sarcoma (MS) is a rare neo-

plastic condition consisting of a tumor mass of myeloid

blasts with or without maturation occurring at an ana-

tomical site other than the bone marrow [1]. MS may

develop as de novo or simultaneously to acute myeloid

leukemia (AML), myeloproliferative neoplasm (MPN) or

myelodysplastic syndrome (MDS) [1]. Hence, MS may

be the first manifestation of AML and precede it by months

or years, or equally represent the initial relapse manife-

station in a previously treated AML. The occurrence of

MS is quite rare. The male:female ratio is 1.2:1 and the

median age is 56 years (range 1 month - 89 years) [1].

The association between tuberculosis and hematolo-

gical neoplasms has been recognized for many years be-

cause of the T-cell immunodeficiency caused by the un-

derlying disease and/or its treatment. However, the diag-

nosis of tuberculosis may be problematic because the

immunodeficiency may attenuate or mitigate its symp-

toms and also symptoms and signs can be overlapped by

those from the hematologic malignancy [2].

The reported prevalence of tuberculosis in patients

with hematologic malignancies is between 0.72% and

2.6% [2]. Conversely, the diagnosis of a simultaneous

occurrence of a rare hematological neoplasm such as MS

and bone tuberculosis at in itial presentation and from the

same involved site seemed quite unusual and due to its

rarity and interest, we aimed to report this case [3-9].

2. Case Report

A 21-year-old female patient presented cough, sore

throat and a suppurative swollen gum for 10 days prior to

Simultaneous Diagnosis of Myeloid Sarcoma of the Jaw and Mycobacterium tuberculosis Infection

1050

hospital admission. Physical examination revealed mod-

erate pallor and swollen inferior gum. Past medical his-

tory included weight loss, fatigue, hypermenorrhea, pre-

vious use of iron salt for anemia and this subject denied

previous expo sure to chemical agents or pesticides. CBC

revealed Hb 6.5 g/dL, hematocrit 18.4% MCV 97 fL

MCH 34 pg, WBC 18.5  109/µL (1 My/3 Bt/69 Sg/ 1

Eo/0 Ba/20 Ly/6 Mo), Platelets 43  109/µL. The

peripheral blood smear presented with 3% blast cells

(type 1) and granulocytic dysplasia (hypogranular cells

and abnormal nuc lei condensation). Bone marrow aspira-

tion, although hemodiluted, was normocellular, G:E ratio

2.4:1 and there were 6.3% type 1 myeloid blast cells (no

Auer rods). Immunophenotyping from bone marrow re-

vealed 10% blast cells positive for CD34, HLA-DR,

CD-117, CD65dim, CD64dim and CD7. Bone marrow bi-

mopsy showed 100% cellularity, 50% of cells were from

granulocytic precursors, there was evident dysplastic

megakaryocytes and fibrosis grade 2. Immuhistochemis-

try studies were positive for lysozyme, MPO in granulo-

ncytic cells and LCA and CD34 in immature cells. Bone

marrow karyotype was unsuccessful due to absence of

metaphases.

Imaging studies revealed lytic jaw lesions not other

bone was involved (CT scans). Abdominal and thorax

CT scans were unremarkable. Bone scan showed increas-

ed uptake in jaw. Gum biopsy showed increased num-

ber of immature cells positive for LCA and MPO favor-

ing the diagnosis of granulocytic sarcoma.

Given the clinical picture and histological findings

thee diagnosis of AML was established: granulocytic sar-

coma with massive gum infiltration (immature granulo-

cytic cells) and 10% of blasts in bone marrow. The pa-

tient was assigned to receive intent of treatment therapy:

induction chemotherapy (3 + 7 cytarabine 100 mg/m2

D1-D7 and daunorub icin 90mg/m2 D1-D3), an d gum tis-

sue culture was positiv e for Mycobacterium tuberculosis.

No other pathogens were found in tissue culture. Simul-

taneously, a qRT-PCR test confirmed the same bacteria

in the gum tissue. Within two concomitant diagnosis tu-

berculosis and myeloid sarcoma in the same topography

the gum biopsy and bone marrow slides were reviewed

by hematology and pathology team both attempts in or-

der to look up and review for any evidence of tuberculo-

sis granuloma and granuloma-associated necrosis but

neither slides and tissue samples did not demonstrate any

of latter. Since jaw tuberculosis was established she was

treated with isoniazid, rifampicin, pyrazinamide and eth-

ambutol ciprofloxacin and amikacin). Curiously, when

tuberculosis reports were available patient was in nadir

after induction. We were concerned that patient could

develop milliary or disseminated tuberculosis but did not

occur.

Complete remission was achieved and the patient was

submitted for consolidation/intensification (HiDAC x3)

schema and referred to allogeneic HSCT. After induction

and full hematological recovery there was no further

evidence or recurrence of fever and lytic lesions. Cur-

rently patient is under CR and ling follow up (48 months)

did not show recurrence of ei t her AML or tu berc ul osi s.

3. Discussion

According to the 4th edition of the WHO classification

(2008), myeloid sarcoma is categorized into AML and

related precursor neoplasms as a distinct pathologic en-

tity [1]. Differential histological diagnosis at conven-

tional light microscopy are lymphoblastic lymphoma,

Burkitt’s or diffuse large B-cell lymphoma or tissue in-

filtration by a non-hematopoietic tumor. As this implies a

wrong treatment, the application of immunophenotyping,

immunohistochemistry is of paramount importance for

the lineage definition, differential diagnosis and specific

treatment.

This case presented several medical challenges. De-

spite the certainty of current MS in the jaw, bone marrow

was not massively infiltrated by abnormal blast cells. In

the present case dysplastic features were evident in bone

marrow and there were no other medical conditions that

could be related to such morphological abnormalities.

Moreover, MS usually occurs in patients with AML,

MDS, or MPN, but it may present as de novo or rarely

precede peripheral blood or bone marrow involvement,

posing a diagnostic challenge. Plus, the gingival/gum/jaw

anatomical site of MS was quite unusual and in addition

patient presented suppurative gum lesion on the same

anatomical site of the MS. This suppurative gum lesion

which was initially managed with large spectrum anti-

biotics and was found to be caused by tuberculosis. After

induction chemotherapy and proper tuberculostatic treat-

ment there were no clinical or radiological recurrence of

suppurative gum or other lesions elsewhere nor dissemi-

nated tuberculosis. Quite often patients who present

tuberculosis may suffer from other medical conditions

that are associated with poor health status, immunode-

ficiency, chronic conditions including but not limited to

chronic alcohol exposure, malnutrition, drug abuse or

other acquired immunodeficiency diseases which were

not found in this case. Systematic tuberculosis screening

was made after jaw culture was positive for M. tubercu-

losis and no other site was involved with mycobacterium

infection. Tuberculosis diagnosis was performed during

nadir and medical attention was given to assess and treat

any other additional infectious disease which did not

occur. To date the course of disseminated tuberculosis is

usually fatal in immunocompromised patients and the

current present case patient presented successful bone

marrow recovery, achieved complete remission and did

Simultaneous Diagnosis of Myeloid Sarcoma of the Jaw and Mycobacterium tuberculosis Infection

1051

not present any further infectious disease complications

throughout AML chemotherapy treatment [2-9].

In a previous survey, tuberculosis was detected in

2.6% (n = 24 in 129) in all hematological neoplasms in a

10-year period [1]. In this published series no tuber-

culosis wa s diagnosed in AML or MS only MD S (n = 2) .

The univariate analysis of that study identified several

factors associated with a high risk of tuberculosis: chro-

nic lymphocytic leukemia, malnutrition (OR 38.78, 95%

CI 2.35 - 639, p = 0.05), previous corticosteroid use and

use of fludarabine. In the case presented we could only

envision poor dental care but not any of the conditions

associated with a high risk tuberculosis.

According to a study published on Leukemia (2007)

[1], with 92 MSs so far evaluated there were no signi-

ficant differences in survivor incidence between the group

with de novo tumor and the one with concomitant or

those ones with a previous hematological disorder. In-

terestingly, all survivors achieved complete remission

following the first line of therapy. By con trast, only eight

out of sixty patients who deceased obtained complete

remission following the initial therapeutic approach. Six

out of seven survivors underwent allogeneic bone mar-

row transplant, the remaining one having received seve-

ral courses of conventional chemotherapy. Notably, ac-

cording to that study, the patients who died of disease

within the group of transplanted patients (two following

Autologous HSCT used as initial therapy and two who

received allogeneic HSCT as salvage therapy) experi-

enced prolonged survival (from 8 months to six years;

mean 41 months). By contrast, the mean survival of the

patients who underwent chemotherapy, imatinibmesylate,

surgery and radiotherapy were as follows: 7.1 months,

5.6 months, 36 days and 1 week respectively. The sur-

vival rates at 48 months of the patients who did and did

not undergo auto/allogeneic HSCT are 76% vs 0%; p =

0.0000. The clinical behavior and response to therapy

were not influenced by age, sex, anatomic site(s) involv-

ed, clinical presentation, previous clinical history, his-

tology type, phenotype and cytogenetic findings. These

data support the indication of bone marrow transplant as

a consolidation therapy. We concluded this patient had a

synchronous diagnosis of myeloid sarcoma and jaw tu-

berculosis.

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