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March 2018-Final Diagnosis and Discussion

The overall morphologic, immunophenotypic and molecular study results are consistent with the diagnosis of extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma).

Discussion (Slide show appears at the end of references)

MALT lymphoma is a low-grade B cell neoplasm of the salivary glands, with the most frequent localization in the parotid gland.  The head-and-neck and often general surgical pathologists play an important role in recognition and subtyping of these lesions.  Lymphoepithelial sialadenitis is believed to be a precursor lesion for salivary gland MALT lymphoma.1  Most patients are in the 55-65 years range with a significant female predilection (F:M = 9:1).2 Interestingly, one of the largest series reported to date, by Troch et al, identified that in 17 of their 21 patients with unilateral parotid MALT lymphoma the lesion involved the left parotid gland.3

Patients usually present with painless enlarging masses typically without B symptoms. Histopathology, supplemented by immunohistochemistry and often molecular pathology, is needed for definitive establishment of diagnosis.  MALT lymphoma of the parotid gland has an indolent clinical course, usually without disseminated disease and most patients can be followed without active treatment.  Infrequent transformation into higher grade lymphomas may require additional therapy; therefore, clinical followup is necessary.

Grossly, the tumors are white-tan firm irregular (non-circumscribed) nodules. Occasionally, interspersed cysts, formed by ectatic ducts, can be noted.

Histologically, the lymphoid infiltrate is represented by confluent sheets with multifocal periductal and centrifugal spread that effaces glandular architecture. So called collars of lymphoid cells surrounding obliterated ducts often have monocytoid appearance. Plasma cell differentiation occurs in 30% of cases. The epimyoepithelial islands consist of ducts that have undergone hyperplasia and frequently show luminal obliteration. The islands frequently contain hyaline material, which is derived from basement membrane. In addition, the islands are infiltrated by both B and T cells. Halos of monocytoid and centrocyte-like B cells surround, progressively invade and destroy the epimyoepithelial islands or “lymphoepithelial islands”3. Colonization of reactive germinal follicles by neoplastic B cells is frequently present. A few large cells are commonly present, and infrequently they can be numerous and form focal aggregates.

Immunohistochemical studies reveal that the lymphoma cells express B cells markers such as CD20 and PAX5. Co-expression of CD43 can aid in the diagnosis of lymphoma as can the demonstration of immunoglobulin light chain restriction by immunophenotypic work-up.    MALT lymphoma1 cells are typically negative for CD10, CD5, BCL6, CD23, and cyclin D1.  In these tumors, neoplastic cells colonizing reactive follicles often show BCL2 positivity as demonstrated in this case (Figure 4). A small subset of MALT lymphoma (<4% of cases) that express CD5 may be associated with a more aggressive behavior.4 Remnants of the epithelial islands can be readily highlighted with keratin immunohistochemistry.

Molecular studies usually detect rearrangement of immunoglobulin heavy and light chains as well as somatic hypermutation of variable regions. Trisomy 3 and 18 are not uncommon in MALT lymphomas, but rather non-specific. The recurrent translocation in salivary gland MALT lymphoma is t(14;18)(q32;q21) involving IgH on chr. 14 and MALT1 on chr. 18. Inactivating mutations, deletions, and promoter hypermethylation of the TNFAIP3 gene (aka A20) have been described by Chanhudet et al in translocation-negative salivary gland lymphomas.5 

Differential diagnosis includes other low grade B-cell lymphomas, myoepithelial sialadenitis and IgG4 related disease (Mikulicz’ disease). Nodular tumors may be confused with follicular lymphoma but neoplastic lymphocytes of this entity are typically positive for CD10 and BCL-6, which were negative in this case. The histologic distinction of myoepithelial sialadenitis from MALToma can be a difficult diagnostic challenge6 and ancillary studies are necessary to exclude clonal lymphoid proliferation. Mikulicz' disease affecting the salivary and lacrimal glands, distinguished by often elevated levels of serum IgG4, infiltration of IgG4+ plasma cells into target tissues, and diffuse swelling, mass formation or fibrosis of affected organs.7

In conclusion, MALT lymphoma of parotid gland is an indolent lymphoid neoplasm, which most often is initially encountered by head and neck or general surgical pathologists. The diagnosis of the parotid gland MALT lymphoma requires, in addition to morphologic examination, extensive diagnostic ancillary workup. Clinical followup is necessary to evaluate for disease dissemination and due to the rare transformation into aggressive lymphoma.  It is important to recognize this entity and be aware of necessary diagnostic modalities to establish the diagnosis, including immunohistochemistry and molecular studies.

A brief clinical followup: The patient remained asymptomatic and visited the oncologist shortly after the diagnosis was established. The oncologist recommended PET imaging to assess dissemination of the disease.  There was no evidence of disease elsewhere by imaging. At a 6-month followup appointment, the patient remained asymptomatic and was cleared to spend cold winter months in Florida.

References

1.        El-Naggar AK, et al WHO Classification of Head and Neck Tumors. Tumors of salivary glands. Hematolymphoid tumours. Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) by Cheuk W and Ott G. 4th ed.  Lyon, 2017. 201-202

2.        Troch M et al. Clinicopathological aspects of mucosa-associated lymphoid tissue (MALT) lymphoma of the parotid gland: a retrospective single-center analysis of 28 cases. Head Neck. 2011; 33(6):763-7.

3.        Thompson, LD. Head and Neck Pathology: A Volume in Foundations in Diagnostic Pathology Series. 1st ed. Churchill Livingstone, 2006.

4.        Wenzel C, et al. CD5 expression in a lymphoma of the mucosa-associated lymphoid tissue (MALT)-type as a marker for early dissemination and aggressive clinical behavior. Leuk Lymphoma. 2001. 42:823-9. PMID  12712477.

5.        Chanudet E, et al. A20 deletion is associated with copy number gain at the TNFA/B/C locus and occurs preferentially in translocation negative MALT lymphoma of the ocular adnexa and salivary glands. J Pathol. 2009. 217: 420-30. PMID 19006194.

6.        Abbondanzo SL. Extranodal marginal-zone B-cell lymphoma of the salivary gland. Ann Diagn Pathol. 2001 Aug;5(4):246-54. Review. PMID:  11510008

7.        Liu AC, et al. Non-Hodgkin's lymphoma mimicking Mikulicz disease: a case report. 2016 Dec 18;48(6):1074-1076. PMID: 27987516


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