Intraoral myeloid sarcoma presenting as toothache and gingival mass

Abstract

A female patient in her 70s with a medical history of myelodysplastic neoplasm presented to the outpatient department with a 4-month history of toothache, painful gingival swelling and loose teeth that required extractions. Intraoral examination revealed a swelling in the lower anterior portion of the mandible, which displaced her teeth. Incisional biopsy of the gingival lesion revealed dense aggregates of atypical round cells which stained positive for CD43, CD45, CD33 and myeloperoxidase, consistent with myeloid sarcoma. Subsequent bone marrow biopsy displayed hypercellular marrow with immature myeloid elements and 21% myeloblasts by flow cytometry, compatible with diagnosis of acute myeloid leukaemia (AML). The patient initially went into remission after treatment but later died of AML relapse after 18 months.

Background

Myeloid sarcoma (MS), also known as granulocytic sarcoma, myeloblastoma or chloroma, is a rare extramedullary malignant tumour consisting of myeloid cells with or without maturation, which efface the normal local tissue architecture.^1–3 It has a predilection for adults between 60 years and 70 years,⁴ and the tumour generally presents with a green colour due to expression of myeloperoxidase (MPO) in the tumour cells.^{4 5} MS may develop de novo or occur concurrently with acute myeloid leukaemia (AML), chronic myeloproliferative disorders or myelodysplastic neoplasm (MDS).^{1 6} When it predates leukaemia at which bone marrow (BM) aspiration and biopsy reveal no haematological disease, it is designated as a primary or isolated MS, and when associated with underlying haematological malignancy, it is referred to as secondary MS.⁷ Although MS can occur at any part of the body, it has been reported more often in the skin, soft tissues, bone and lymph node.^4–6 Oral cavity MS is extremely rare, and its exact prevalence is unclear due to its low incidence.⁸ To the best of our knowledge, there are only eight case reports of intraoral MS in patients with MDS in the English literature. We report a rare case of intraoral MS in a female patient in her 70s who initially presented with toothache and gingival mass, as an unfamiliar initial manifestation of MS.

Case presentation

A female patient in her 70s with a medical history of MDS presented to the outpatient clinic with a 4-month history of toothache and painful gingival swelling. The patient reported associated loose teeth that required three tooth extractions over the same period of time. Intraoral examination revealed a soft swollen gingival mass with irregular surfaces in the anterior portion of the mandible that displaced her teeth (figure 1).

Figure 1.

Intraoral lesion in the anterior region of the right mandible.

Investigations

At presentation, the patient was pancytopenic, with a haemoglobin concentration of 7.4 g/L, white blood cell count of 1.3×10⁹/L, platelet count of 65×10⁹/L and neutrophil count of 0.35×10⁹/L (28.4%). The previous complete blood count profile of the patient did not evolve to necessitate BM biopsy prior to the diagnosis of MS. Three months prior to the diagnosis of MS, haemoglobin was 8.3 g/L, white blood cell (WBC) count was 1.2×10⁹/L, and platelet count was 61×10⁹/L. One month prior to the diagnosis of MS, haemoglobin was 7.3 g/L; WBC count was 2.1×10⁹/L; and platelet count was 41×10⁹/L. Incisional biopsy of the gingival lesion was carried out under local anaesthesia. Histological section using H&E staining revealed diffuse infiltration of gingival connective tissue by sheets of poorly differentiated haematopoietic cells (figure 2) and dense aggregates of atypical round cells (figure 3). Immunohistochemical stains were strongly positive for CD33, CD43, CD45, Ki-67 and MPO, suggestive of MS (figures 4–6). Subsequent BM biopsy displayed hypercellular marrow with immature myeloid elements and 21% myeloblasts by flow cytometry compatible with diagnosis of AML (figures 7 and 8).

Figure 2.

Histological slide showing diffuse infiltration of gingival connective tissue by sheets of poorly differentiated haematopoietic cells.

Figure 3.

Histological slide showing dense aggregates of atypical round cells, H&E.

Figure 4.

Tumour cells showing strong positivity for CD43.

Figure 5.

Tumour cells showing strong positivity for Ki-67.

Figure 6.

Tumour cells showing strong positivity for MPO.

Figure 7.

Hypercellular bone marrow with immature myeloid elements.

Figure 8.

Bone marrow showing 21% myeloblasts by flow cytometry (acute myeloid leukaemia).

Differential diagnosis

Due to non-specific clinical manifestation of oral MS, it is important that clinicians keep a broad differential diagnosis. Clinically, the differential diagnoses for oral MS include odontogenic and periodontal infections, reactive gingivitis, drug-induced gingival hyperplasia, pyogenic granuloma, salivary gland tumours and acute leukaemic transformations of chronic myeloproliferative neoplasms (MPNs) or blast crisis of chronic myeloid leukaemia. In our patient, since there was no fever or purulence and because the lesion was unresponsive to periodontal therapy, infection was lower on the differential diagnosis list. Furthermore, early biopsy and correct diagnosis were made because of prior history of MDS.

Treatment

The patient received treatment regimen comprising venetoclax and azacitidine. Subsequent to her treatment, the patient developed febrile neutropenia and her hospital course was complicated by Staphylococcus aureus bacteraemia, which was treated with systemic antibiotics. She also received 4 units of packed red blood cells over the course of her treatment.

Outcome and follow-up

The patient initially went into remission after treatment; however, she later died of AML relapse after 18 months.

Discussion

MDSs are a group of haematological malignancies characterised by clonal haematopoiesis, one or more cytopenias (ie, anaemia, neutropenia and/or thrombocytopenia) and abnormal cellular maturation.³ The fifth edition of the WHO Classification of Hematolymphoid Tumours replaced the term ‘myelodysplastic syndrome’ with ‘MDS’ to underline their neoplastic nature and to harmonise their terminology with MPN.⁹ MDS shares clinical and pathological features with AML, but MDS has a lower percentage of blasts in peripheral blood and BM (by definition, <20%).^{1 3} WHO classification requires greater than 20% blasts in the blood or BM for diagnosis of AML except in leukaemias with certain genetic abnormalities, such as those with t(8;21), inv(16) or t(15;17), and MS, which are considered diagnostic of AML without regard to the blast count.^{2 3} MS is a solid, localised tumour composed of mature or immature cells of granulocytic lineage present at an anatomical site beyond the bone.¹⁰ The WHO classifies MS as a unique tissue-based manifestation of AML which may present de novo, as a relapse of AML, or as a transformation of prior MDS or MPN.⁹

The clinical presentation of MS depends on its location, and the presenting symptoms usually occur due to mass effect exerted by the tumour or organ dysfunction due to infiltration.¹⁰ Clinical presentations of oral MS are diverse and non-specific. The most commonly involved anatomical sites in the oral cavity are the gingiva (>65%), hard palate (20%), other mucosa (alveolar, buccal and lip) (10%), and tongue and salivary gland (5%).⁴ According to Wang et al, the most frequent clinical finding for both primary and secondary oral MSs are diffuse gingival swelling (50%) and localised swelling or mass (30%); ulcers are the rarest presentations. Our patient had a unilateral localised swelling, which is one of the the most common presentations.

Clinical diagnosis of MS is difficult, and definitive diagnosis can only be made with histological and immunohistochemical tests.⁶ Without history of haematological malignancy, patients with oral lesions can have initial misdiagnosis. Common initial diagnoses include periodontal disease and inflammatory or reactive lesions. In a literature review of oral MS cases conducted by Wang et al, the median time from initial presentation to correct diagnosis of primary MS was 4 months compared with 3 weeks for secondary MS.⁴ Pathological evaluation helps to rule out inflammatory and reactive hyperplasia, periodontal conditions, infections and malignancies. Immunohistochemical studies help in reaching a definitive diagnosis because myeloid cells react to antibodies against myeloid-associated antigens and enzymes such as lysozyme, MPO and chloroacetate esterase.^{6 10} CD43 and lysozyme are deemed as the most sensitive markers for MS based on reported 100% expression in a majority of case studies.¹⁰ Oral MS is an uncommon manifestation of AML, and it is seen in less than 1% of patients.^{11 12} However, in most patients with MS, AML develops in the next few months to years.¹⁰ Therefore, investigation and further follow-up for systemic haematological malignancy are essential.

The overall prognosis of patients with intraoral MS is poor and highly related to the clinical course of AML.^{6 13} The median overall survival reported from prior investigators ranged from 5 months to 40 months.^{14 15} Although there is no consensus on MS treatment, the current recommended treatment regimen for isolated MS or MS that is concurrent with AML is conventional AML protocol.^{10 16–18} Local treatment include radiotherapy, surgery or both.

Patient’s perspective.

Next of kin perspective (daughter)

We were optimistic. I wish we knew how bad it was and how poor the prognosis was. She was in excruciating pain and suffered from the treatment course. Furthermore, we were frustrated because she was not eligible for stem cell transplantation. Despite all this, we are proud of her for fighting hard.

Learning points.

• Myeloid sarcoma (MS) is encountered rarely in the oral cavity; the diagnosis depends on histological and immunohistochemical tests.

• All physicians and dental clinicians should keep the possibility of intraoral MS in mind and carefully examine patients with gingival swelling especially in patients with underlying haematological disease.

• Current treatment of MS includes chemotherapy, radiotherapy and surgery.

Ethics statements

Patient consent for publication

Consent obtained from next of kin.