Large-cell diffuse lymphoma of B-cell phenotype

A 39-year-old male without known allergies or toxic habits, and with a history of arterial hypertension, hypercholesterolemia and dilated myocardiopathy subjected to heart transplantation 10 years before (with immunosuppressive treatment since then) presented with a tumor in the right maxillary gingival region.
The lesion had been present for the past three months and was described as painful.

Exploration revealed an upper maxillary tumor extending from 1.1 to 1.4, and bulging on the palatal side. The mucosa appeared slightly erythematous but intact.
The computed tomography informed of a lytic lesion affecting the right medial-lateral portion of the maxilla, with rupture of both cortical layers.
A large soft-tissue component was noted, measuring about 26 x 19 mm, displacing the dental structures and affecting the nasal septum and wall of the maxillary sinus.

The biopsy indicated high-grade lymphoma.

 

DISCUSSION

The first diagnosis to be considered in the presence of a palatal swelling is infection – mainly an abscess of dental origin, in view of the proximity of the dental apexes. This etiology was discarded, however, since no dental pathology was noted either clinically or radiologically. Moreover, the manifestations were suggestive of a process with a lesser inflammatory-infectious component.

In this same context, we had to consider the possible presence of a cyst located in the maxilla and which could cause swelling secondary to overinfection – related or not to the teeth. Computed tomography subsequently indicated a more aggressive lesion, due to destruction of the cortical layers.

Another possible diagnosis was a salivary gland neoplasm. These tumors represent 3% of all head and neck neoplasms, and minor salivary gland tumors in turn account for 10-15% of all salivary gland neoplasms (1). They are more common in women, with a proportion of 1.2:1 to 1.9:1 over males (2). In the palatal region the usual location is the junction between the soft and hard palate, on one side of the midline, and corresponding to the distribution of the mucosal glands in the palate. The classification of salivary gland tumors is subject to constant revision, though it is known that the smaller the gland the greater the risk of lesion malignancy. In this sense, 10% of parotid gland tumors are malignant, versus 30% of all submandibular gland tumors, and 50% of the intraoral salivary gland tumors.
Neoplasms of the palatal salivary glands are divided into benign tumors, locally aggressive tumors, and malignant tumors with metastatic potential.
The proportion of malignant palatal salivary gland tumors is 50%.
The most common locally palatal tumor is pleomorphic adenoma, while the most frequent malignancies include mucoepidermoid carcinoma, cystic adenoid carcinoma, or low-grade polymorphic adenocarcinomas.
Clinically, the lesions are characterized by a smooth tumor, with an intact overlying mucosa, and scant mobility in response to palpation. Secondary ulceration may develop due to intrinsic tumor growth or trauma (3).
The differential diagnosis includes gingival lesions of inflammatory origin (pyogenic granuloma, etc.) that may appear in the gingival tissue associated to some local irritative factor. In the absence of such a factor, we must consider giant cell lesions or a peripheral odontogenic tumor (peripheral odontogenic fibroma, peripheral ameloblastoma, etc.) which, although infrequent, are also possible. The histological study of the lesion provides an orientation (4).

Finally, another diagnosis to be considered is lymphoma – as confirmed by biopsy in our patient (specifically, large-cell diffuse lymphoma of B-cell phenotype).

Malignant lymphoproliferative processes are the most important leukocyte disorders. In lymphoid neoplasms, the phenotype of the tumor cells is similar to that of a given differentiation stage of normal lymphocytes. In this sense, some neoplasms exhibit precursor forms or earlier differentiation cell forms, while others express as mature differentiated or peripheral cells.
Among the lymphoid neoplasms, a distinction can be made between lymphomas and leukemias – the former corresponding to isolated tumor masses, and the latter to diffuse tumors of the bone marrow compartment.

The histological classification of lymphomas has been a source of frustration for many years for both clinicians and pathologists. In 1994 the journal Blood published a classification of lymphoid cell neoplastic processes proposed by the International Lymphoma Study Group, and referred to as the REAL Classification.
This classification does not propose new disease entities but rather classifies the real disorders seen in daily practice (5), based on morphological, immunological and genetic techniques (6).

These observations have been adopted in the latest modification of the World Health Organization, which acknowledges three categories according to the morphology and cell lineage involved: B cell lymphomas, T cell and natural killer (NK) cell lymphomas, and Hodgkin lymphomas – with differences in terms of the clinical and histological characteristics, and approaches to treatment (7).

The origin of non-Hodgkin lymphomas (NHLs) is usually unknown, though some subtypes have been related to infections (Epstein Barr virus, EBV) – as in the case of Burkitt’s lymphoma – while others are associated with intrinsic or acquired immune suppression, as in the case of transplant patients. Indeed, organ transplantation is the factor most clearly related to the development of lymphoma (as in our patient, who underwent a heart transplant 10 years previously).

Another possible origin of such tumors involves genetic alterations, though the NHL genome is quite stable (8).

Clinically, affected patients can present general symptoms such as weight loss, fever, nocturnal perspiration, etc., or localized tumor lesions in lymph nodes (less than 25% of all NHLs) or outside the lymph nodes (i.e., extranodal forms)(9). In the oral cavity, the principal manifestation of lymphoma is swelling, principally in the region of the soft palate. This symptom is very common among tumors developing in this region – as a result of which the differential diagnostic range is considerable 10).

Large-cell diffuse lymphoma of B-cell phenotype is the most frequent NHL.
As in our patient, the clinical expression consists of rapidly-growing tumors commonly associated with general symptoms.

Histochemical study shows the tumor B cells to express CD19, CD20, CD22 and CD10 (11). Our patient exhibited positivity to CD79, CD20 and bc12, with a Ki-67 proliferation index of 70-75%. Large-cell diffuse lymphoma of B-cell phenotype was diagnosed.

The prognosis is related to the specific biology of each type of lymphoma, and to the clinical characteristics of the patient (12).
Large cell diffuse lymphoma can be treated successfully with chemotherapy either alone or in combination with radiotherapy (13).

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