Although as a group NHL is the second most common malignancy presenting within the head and neck region, involvement of the head and neck by MCL is unusual and the primary presentation of MCL within the oral cavity is rare.3,4,6-16
To our knowledge, this is the largest reviewed series of MCL arising within the oral cavity that has been reported in the English literature. The pathologic and demographic findings of our 2 patients are generally consistent with those of the 7 previously reported cases.
MCL is an uncommonly encountered B-cell neoplasm characterized by small to medium-sized lymphoid cells.1-3
Antiquated diagnostic terminologies of this entity include intermediate lymphocytic lymphoma, centrocytic lymphoma and mantle zone lymphoma.2,17,18
In 1992, Banks et al.
introduced the term mantle cell lymphoma that was subsequently adopted by the WHO in 2001 and is currently the favored nomenclature.1,2
Despite recent data showing an increase in the incidence of MCL to 0.55/100,000/yr persons, it remains one of the least common B-cell malignancies. Depending on the study, MCLs accounts for between 6 and 10% of all B-cell lymphomas.3,19
Although the majority of MCLs occur in lymph nodes, many patients have extranodal involvement with the spleen, gastrointestinal tract and Waldeyer’s ring being the most commonly affected sites.3,19
The typical microscopic appearance of extra-nodal MCL is that of a monomorphic lymphocytic infiltrate that destroys the native architecture, and organizes itself in solid sheets or in vague nodules. Small, hyalinized vessels frequently support this malignant infiltrate. Cells are small to medium-sized and nuclei are oval to round with typically inconspicuous nuclei. In this setting, the typical immunophenotype for MCL is a B-cell lymphoma expressing CD20 antigen, co-expressing CD5 and CD43 and negative CD23 antigen expression.2
The chromosomal translocation t(11; 14) (q13; q32), which results in the juxtaposition of the cyclin D1 (bcl-1) gene locus to the Ig heavy chain promoter, is a characteristic, but not universal, molecular feature of this lymphoma subtype.20
This translocation results in the characteristic overexpression of CCND1 protein, a driver of G1/S progression.
The primary entities in the differential diagnosis include marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), and follicular lymphoma (FL). MZL is relatively more common in the oral cavity particularly in the setting of autoimmune exocrinopathy sharing some microscopic similarities with MCL.21
However, MZL is characterized by small to medium-sized neoplastic cells that are CD20+ but negative for CCND1 and CD5. SLL is a neoplastic proliferation of non-activated, mature-appearing small lymphocytes. Like MCL, it is typically CD5 positive; however, it lacks CCND1 expression. The finally FL, composed of follicular center B lymphocytes, shows positive staining for CD10 but fails to express CD5, CD43 or CCND1.2
Both the blastoid-variant MCL (BV-MCL) and the pleomorphic variant MCL (PV-MCL) are aggressive MCL subtypes. Although some believe these entities represent variants along the same spectrum, the WHO has recognized these two as distinct subtypes.2
BV-MCL is characterized by cells that resemble lymphoblasts with unusually high mitotic rates (>= 20-30/10hpf). Unlike conventional MCL, extra copies of the CCND1 gene characterize BV-MCL and the proliferation rate, as can be assessed by the expression of Ki67 antigen, is in excess of 50%.22,23
This variant more commonly affects older patients and has a shorter response duration after first-line therapy.23
PV-MCL, similar to BV-MCL, is histologically unique with large, pleomorphic cells that have round to oval nuclear contours, pale cytoplasm and with, at least some cells having, prominent nucleoli.2
Similar to previously published cases, our series of oral cavity MCL occurred more commonly in older men.5, 24-26
The finding of a mass, which may or may not be ulcerated, is the most common oral manifestation of NHLs.9,27
Eight of the 9 patients in this series presented with a mass. Treatment provided to these patients varied from combination chemotherapy to chemotherapy and radiotherapy to observation. Typically, MCL has a relentless clinically aggressive course that is resistant to therapy and a mean survival of only 3 years.2,28,29
In keeping with the previously published poor prognosis for MCL, 4 of 9 patients were dead of disease at a mean of 21 months.
We conclude that although NHL is the second most common malignancy to affect the head and neck, MCL of the oral cavity is a very uncommon diagnosis. In keeping with other NHLs, most oral MCLs occur in an elderly male population and have a possible predilection for the palate. The microscopic diagnosis can be challenging given its similar appearance to other small cell lymphomas requiring a comprehensive immunohistochemical panel for the accurate diagnosis. Like MCL occurring in other sites in the body, the prognosis and outcome of oral MCL appears to be poor.