Myoepithelial Sialadenitis Research Articles

Literature Review of Sebaceous and Non-Sebaceous Lymphadenoma

Lymphadenoma of the salivary gland is a rare form of tumor that can be branched into Sebaceous Lymphadenoma (SLA) and Non-Sebaceous Lymphadenoma (NSLA). It is painless, hyperdense, shiny yellowish/brownish unicystic or multicystic mass which is encapsulated and well defined having lymphocytic and/or lymphoid follicles background present with or without sebaceous differentiation. Both SLA and NSLA are predominantly located in parotids with occasional case appearing in minor salivary glands and has <100 and <50 reported cases respectively in English literature. We have attempted to compile reported case studies on SLA and NSLA and tried to make analysis on the basis of findings. Our analysis revealed that both SLA and NSLA are often non-malignant in nature but feature of malignancy cannot be completely ruled out. Data also found that SLA and NSLA has a significant gender bias towards males but NSLA is more likely to appear at an early age as compared to SLA which often emerge after the 5th decade of life. Further, differential diagnosis should be considered to distinguish SLA and NSLA from Warthin’s tumor, pleomorphic adenoma, mucoepidermoid carcinoma, cystadenoma, lymphoepithelial cysts, myoepithelial sialadenitis, malignant lymphoma and metastatic adenocarcinoma of lymph node. This review discusses various techniques used in the past studies that can be helpful in making differential diagnosis.

Benign Lymphoepithelial Lesion of Parotid Gland and Secondary Amyloidosis as Concurrent Manifestations in Sjögren's Syndrome.

Benign Lymphoepithelial Lesion of Parotid Gland and Secondary Amyloidosis as Concurrent Manifestations in Sjögren's Syndrome.

SAT0205 Blys up-regulation and salivary clonal B-cell expansion characterize sjögren’s syndrome-related lymphoproliferative disorders and correlate with the new ESSDAI score

BackgroundPrimary Sjögren’s syndrome (SS) is characterized by an increased risk of lymphoma in patients with prelymphomatous manifestations (i.e., myoepithelial sialadenitis (MESA) or mixed cryoglobulinemia). Increased levels of B-lymphocyte stimulator (BLyS)...

BLyS upregulation in Sjogren's syndrome associated with lymphoproliferative disorders, higher ESSDAI score and B-cell clonal expansion in the salivary glands

Primary SS is characterized by an increased risk of lymphoma in patients with prelymphomatous manifestations (i.e. myoepithelial sialadenitis or mixed cryoglobulinaemia). Serum B-lymphocyte stimulator (s-BLyS) levels in SS-related B-cell lymphoproliferative disorders were studied by integrating the results with the disease activity score and with molecular analyses of B-cell expansion in the salivary glands. Seventy-six primary SS patients (with or without lymphoma or prelymphomatous manifestations), 56 HCV-related cryoglobulinaemic vasculitis patients and 55 controls were studied. s-BLyS and molecular analyses of B-cell expansion in the salivary gland tissues were performed. Patients with SS and persistent parotid swelling underwent parotid biopsy. s-BLyS differed between SS subgroups, higher levels being documented in patients with lymphoma or prelymphomatous manifestations vs SS without [1.85 (0.45-4.12) ng/ml vs 1.12 (0.56-1.98) ng/ml; P < 0.0001]. s-BLyS levels significantly correlated with the European League Against Rheumatism (EULAR) SS disease activity index (r = 0.62, P < 0.0001, Spearman's test). Clonal B-cell expansion in the salivary glands, but not polyclonal B-cell expansion, was associated with higher s-BLyS levels [1.98 (0.45-4.12) ng/ml vs 1.15 (0.56-3.25) ng/ml; P = 0.013)]. Higher s-BLyS levels and tissue clonal B-cell expansion characterize SS with B-cell lymphoproliferative disorders, even at prelymphomatous stages. This subgroup of SS patients showed the highest EULAR SS disease activity index scores. This represents a biologic rationale for targeting both clonal B-cell expansion and s-BLyS overproduction in SS.

Cryoglobulinaemia related to Sjogren's syndrome or HCV infection: differences based on the pattern of bone marrow involvement, lymphoma evolution and laboratory tests after parotidectomy

The relationship of cryoglobulinaemia with lymphoproliferation of mucosa-associated lymphoid tissue (MALT) as risk factors for lymphoma evolution in SS remains to be clarified. The different biologic background of SS-related cryoglobulinaemia as compared with cryoglobulinaemia linked to HCV infection was clarified by different clinical and biologic approaches. B-cell clonal expansion was analysed in the bone marrow of 27 consecutive cases with primary SS and mixed cryoglobulinaemia, HCV unrelated, in comparison with 55 HCV-related patients with cryoglobulinaemic vasculitis (CV) without SS. The results were related to the possible occurrence and localization of B-cell lymphoma in the single case. Secondly, the prevalence of mixed cryoglobulinaemia was investigated in 41 unselected patients with primary SS showing either parotid myoepithelial sialadenitis (MESA) or a frank B-cell non-Hodgkin's lymphoma. Thirdly, the levels of serum cryoglobulins and RF were followed in one patient with primary SS, CV and parotid B-cell lymphoma of MALT after bilateral subtotal parotidectomy. A polyclonal pattern of B expansion in the bone marrow was significantly more frequent in SS-related (19/27 cases) than in HCV-related cryoglobulinaemia (19/55) (P = 0.003). Cryoglobulins were positive in a fraction of patients with SS and malignant lymphoma or with parotid MESA (13/18 and 7/23, respectively), whereas MALT involvement by the lymphoproliferative disorder was the rule. Finally, the levels of serum cryoglobulins and RF markedly decreased in the SS patient undergoing bilateral subtotal parotidectomy. Lymphoproliferation of MALT appears as the biologic background of cryoglobulinaemia in SS, differently from HCV-related cryoglobulinaemia.

Primary non‐hodgkin's lymphomas of the major salivary glands

The clinical course of primary salivary gland lymphomas has received little attention. We retrospectively assessed 20 patients with previously untreated non-Hodgkin's lymphomas (NHLs) and histologically confirmed as having parenchymal involvement of the salivary glands. The clinical presentation, therapy, and outcomes were compared between the 12 patients with mucosa-associated lymphoid tissue (MALT) lymphomas and the 8 patients with other NHLs. At diagnosis, the 12 patients with MALT lymphoma had a greater mean age and longer duration than did the 8 patients with other NHLs (P < 0.05). Eight of the 12 MALT lymphoma patients had recurrent episodes of salivary gland swelling and 5 had myoepithelial sialadenitis, Sjögren syndrome, or gastric MALT lymphoma; these were not observed in the 8 other NHL patients. Compared with the latter group, the MALT lymphoma group had significantly greater five-year relapse-free (37.5% vs. 91.7%, P < 0.05) and disease-free (35.0% vs. 90.9%, P < 0.05) survival rates. However, two MALT lymphoma patients with high-grade transformation had recurrences beyond the head and neck region. Understanding the distinct clinical presentation and course of primary salivary gland lymphomas may help guide the proper diagnosis and management of patients with these tumors.

Genetic alterations underlying the pathogenesis of MALT lymphoma.

Extranodal marginal zone B-cell lymphoma is a discrete clinicopathologic entity arising in mucosaassociated lymphoid tissue (MALT), characterised by unique pathogenic, histologic and clinical features. MALT B-cell lymphoma occurs more frequently in organs, such as stomach, salivary glands, or thyroid, which acquire lymphoid tissue only after chronic phlogistic events. This occurs in response to either infectious conditions such as Helicobacter pyloriassociated chronic gastritis, or autoimmune processes like myo-epithelial sialadenitis and Hashimoto's thyroiditis. Within these prolonged lymphoid reactive proliferations, an abnormal B cell clone arises and replaces the normal population, giving rise to the MALT lymphoma. Clinical studies have shown that gastric MALT lymphoma can regress after anti-H. pylori antibiotic treatment, even if it is still not known whether antibiotics alone might induce de®nitive cure of the lymphoma. The molecular events underlying MALT lymphoma pathogenesis have become clearer during these last years and, at least for gastric lymphoma, a model can be drawn (Figure 1). Two distinct pathways seem to occur. MALT lymphoma might develop through a series of genetic lesions underlying the progression from a H. pylori-dependent lymphoma, with the presence of H. pylori strain-speci®c T cells necessary for the growth of lymphoma cells, to a H. pyloriindependent lesion. In contrast, the occurrence of the translocation t(11;18) would give rise to a MALT lymphoma, already H. pylori-independent. t(11;18)(q21;q21): API2-MALT1 fusion protein

Value of minor salivary gland biopsy in diagnosing Sjögren's syndrome.

Minor salivary gland biopsy is suggested for diagnosing Sjögren's syndrome in patients with clinical signs of sicca syndrome. This biopsy is mainly examined on the basis of the semiquantitative morphologic criteria without taking into account the detection of characteristic myoepithelial sialadenitis (MESA). The role of minor salivary gland biopsy in the diagnosis of Sjögren's syndrome as a possible detection method for MESA was examined in a retrospective study. Minor salivary gland biopsies were obtained from 32 patients between 1986 and 1996. Twenty-two patients fulfilled the criteria for primary and 10 patients for secondary Sjögren's syndrome based on the catalogue of the European Study Group on Diagnostic Criteria for Sjögren's Syndrome. The histopathologic assessment was based on the histomorphologic MESA criteria, that is, parenchymatrophy, interstitial lymphocytic cell infiltration, and myoepithelial cell islands. The histopathologic assessment revealed normal minor salivary glands in 37.5% of the cases and chronic sialadenitis in 59.4% of the patients. Only one female patient (3.1%) had changes characteristic of MESA. Minor salivary gland biospy is therefore an unsuitable method for detecting MESA if the pathomorphologic correlative of MESA is used to confirm the diagnosis of Sjögren's syndrome.

Extranodal marginal-zone B-cell lymphoma of the salivary gland.

Primary non-Hodgkin's lymphoma of the salivary gland is an uncommon tumor that most often occurs in the parotid gland. The most common subtype is marginal-zone B-cell lymphoma, extranodal, mucosa-associated lymphoid tissue type. This subtype has recently been included in the Revised European-American Classification of Lymphoid Neoplasms, as well as in the upcoming World Health Organization classification of hematopoietic and lymphoid neoplasms. This low-grade lymphoma usually arises in a background of benign lymphoepithelial lesion or myoepithelial sialadenitis that is associated with the autoimmune disease Sjögren's syndrome. It occasionally develops in patients who do not have a history of autoimmune disease. When mucosa-associated lymphoid tissue lymphoma occurs in the salivary gland, as in other extranodal sites such as the stomach, it is usually an indolent neoplasm that tends to remain localized for long periods of time, even without treatment. Eventually, however, the tumor may disseminate or transform to a higher grade. The histologic distinction of myoepithelial sialadenitis from low-grade B-cell mucosa-associated lymphoid tissue lymphoma can be a difficult diagnostic challenge and many of these lesions continue to be ambiguously diagnosed as "pseudolymphoma." Immunophenotypic or flow cytometric analysis may be useful in showing an aberrant phenotype or immunoglobulin light-chain restriction, which helps to support a diagnosis of malignant lymphoma in most cases. Molecular genetic analysis for immunoglobulin gene rearrangements also may be useful in showing monoclonality, although the exact significance of this finding in some cases remains controversial.

Chemokines and cell trafficking in Sjögren's syndrome.

Sjögren's syndrome is a chronic inflammatory condition affecting exocrine glands, manifested clinically as dry eyes and dry mouth. It arises secondary to systemic immune-mediated diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), scleroderma or 'primary' Sjögren's syndrome. Histologically it is characterized by peri-ductal aggregates of CD4 T lymphocytes, the frequent occurrence of ectopic germinal centres and, in some patients, B-cell infiltration of ductal epithelium (myoepithelial sialadenitis). This latter lesion is the precursor for the development of low grade (MALT) B-cell lymphoma. The identification over recent years of chemokines and their receptors enables us to address the specific processes involved in the migration of inflammatory cells into exocrine glands, the development of their secondary structures and patterns of retention within the glands and potentially the subsequent transformation of B cells into mucosa associated lymphoid tissue (MALT) lymphoma.

Pathological features of lymphoid proliferations of the salivary glands: lymphoepithelial sialadenitis versus low-grade B-cell lymphoma of the malt type.

Lymphoid proliferations of the salivary glands can be either reactive or neoplastic. Reactive lesions include the lymphoepithelial sialadenitis (LESA; also known as myoepithelial sialadenitis [MESA]) of Sjogren's syndrome. Lymphomas of the salivary glands are predominantly B-cell type and include extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type. The spectrum of histopathologic features of LESA/MESA includes 1) "fully benign lymphoid infiltrate," with or without an associated lymphoid follicular structure, without immunoglobulin (Ig) light chain restriction in B-cells, and without any features of aggressive behavior, and 2) "lymphoproliferative lesions," with or without areas of Ig light chain restriction in B-cells, with the usual presence of centrocyte-like cells. A more or less pronounced lymphoepithelial aggressiveness may be present without definite evidence of malignancy. B-cell clones are detected in over 50% of cases of LESA/MESA by molecular genetic methods, but this does not correlate with morphological or clinical evidence of overt lymphoma. On the other hand, "marginal zone B-cell lymphoma of the MALT type" of the salivary glands produces a dense lymphoid infiltrate diffusely involving the gland, with obliteration of acini. The centrocyte-like cells form broad "halos" around the epithelial cell nests and broad strands between lymphoepithelial lesions, often linking together several lymphoepithelial lesions. Further, lymphoma cells express monotypic surface Ig, and in the majority of the cases, the plasma cells are also monoclonal. In conclusion, the diagnosis of LESA/MESA versus marginal zone B-cell lymphoma of the MALT type still relies on the evaluation of morphological features. It seems that molecular genetic analysis has little or no practical role in the clinical diagnosis of salivary gland lymphoma in a setting of LESA/MESA and Sjögren's syndrome.

Epstein-Barr virus status and the histopathological changes of parotid gland lymphoid infiltrates in HIV-positive children

This study examined the EBV status and the morphology in parotid glands of a large cohort of HIV-positive pediatric patients. Nineteen children with vertically acquired HIV infection, ranging in age from three months to seven years and two months, were analyzed. Seventeen patients were assessed for serological evidence of EBV infection; nine showed evidence of past infection, one each re-activation and current infection and six did not have serological evidence of EBV. Immunohistochemistry and in situ hybridization for EBER 1 and 2 were performed on formalin-fixed, paraffin-embedded tissue. Fourteen of the 19 cases were classified as severe or established myoepithelial sialadenitis (MESA) and five were regarded as having mild MESA. The majority of intraepithelial lymphocytes were of B-cell lineage, while the pericystic infiltrate contained CD8-positive T-lymphocytes. p24 immunohistochemistry for HIV showed positive follicular dendritic cells, lymphoid cells and macrophages. Ten of 14 cases were positive for EBER 1 and 2. These included cases that were serologically negative for EBV. This study confirms that the morphology and immunophenotype of pediatric HIV-associated parotid lesions are similar to those seen in adults. Ten of 14 cases with evidence of EBV within the lymphoid infiltrate showed the same morphology and immunophenotype as cases in which EBV was not detected either by serology or by in situ hybridization. These findings indicate that EBV is not uniformly found in either the tissue or serum of these patients, and may not have a pathogenetic role in HIV-associated lymphoepithelial lesions in the pediatric age group.

The value of PCR technique in fine needle aspiration biopsy of salivary gland for diagnosis of low-grade B-cell lymphoma.

In fine needle aspiration biopsy (FNAB) of salivary gland delineation of low-grade B-cell lymphoma from benign lymphoid lesions of myoepithelial sialadenitis (MESA) may be very difficult by means of cytomorphological criteria alone. To improve cytodiagnosis PCR technique was applied on routinely stained smears to determine clonal status by amplifying the third complementarity-determining region (CDR3) of the hypervariable domain of the immunoglobulin heavy chain. Twelve cases diagnosed cytologically as suspicious of low-grade B-NHL with following histology of B-NHL (n = 5) or MESA (n = 7) were analyzed. The CDR3-IgH PCR produced distinct bands in 10/12 cases. The PCR products were analyzed with Genescan software on the DNA sequencer, which demonstrated monoclonal bands in all NHLs and in one case of MESA. The results indicate that PCR technique may be helpful in improving cytodiagnostic accuracy for recognition of low-grade B-NHL of salivary gland.

Clonal Salivary Gland Infiltrates Associated With Myoepithelial Sialadenitis (Sjögren's Syndrome) Begin as Nonmalignant Antigen-Selected Expansions

Myoepithelial sialadenitis (MESA) is the reactive salivary gland lymphoid infiltrate that occurs in patients with Sjogren's syndrome. Although it is well established that mucosa-associated lymphoid tissue (MALT)-type lymphomas may develop from MESA, the issue of whether monoclonal B-cell populations in early MESA-associated lesions represent MALT lymphomas or more benign types of expansions has been very controversial. In addition, it is unknown whether antigen stimulation plays a role in the development or growth of MESA-associated clones. To investigate these issues, we have analyzed the Ig VH genes used by MESA-associated clones in sequential biopsies obtained from contralateral sites of seven different patients. In three cases, single clones were identified in the follow-up biopsies that were distinct from the single clones identified in the initial specimens, whereas in three other cases, the same clone was identified in both the initial and subsequent specimens. In the remaining case, two clones were identified in the second biopsy specimen, one of which was distinct from the initial clone. Of the 11 distinct clones identified in the 14 specimens that were analyzed, 8 were derived from a V1-69 VH gene segment, whereas the other 3 were derived from a V3-7 VH gene segment. In addition, the MESA clones also showed conserved amino acids sequence motifs in their third complementarity-determining regions (CDR3), some of which were encoded by N nucleotides. The marked VH gene restriction along with the similar CDR3 sequences suggests that MESA-associated clones even from different patients may bind the same or similar antigens and are selected for clonal expansion on that basis. The high rates of ongoing VH gene mutation observed in some of the cases futher suggest that the growth of early MESA clones is still dependent on antigen stimulation. In addition, our finding that different biopsies from the same patient may contain distinct clones indicates that some MESA-associated clones have not yet evolved to malignant lymphomas.

Clonal Salivary Gland Infiltrates Associated With Myoepithelial Sialadenitis (Sjögren's Syndrome) Begin as Nonmalignant Antigen-Selected Expansions

AbstractMyoepithelial sialadenitis (MESA) is the reactive salivary gland lymphoid infiltrate that occurs in patients with Sjögren's syndrome. Although it is well established that mucosa-associated lymphoid tissue (MALT)-type lymphomas may develop from MESA, the issue of whether monoclonal B-cell populations in early MESA-associated lesions represent MALT lymphomas or more benign types of expansions has been very controversial. In addition, it is unknown whether antigen stimulation plays a role in the development or growth of MESA-associated clones. To investigate these issues, we have analyzed the Ig VH genes used by MESA-associated clones in sequential biopsies obtained from contralateral sites of seven different patients. In three cases, single clones were identified in the follow-up biopsies that were distinct from the single clones identified in the initial specimens, whereas in three other cases, the same clone was identified in both the initial and subsequent specimens. In the remaining case, two clones were identified in the second biopsy specimen, one of which was distinct from the initial clone. Of the 11 distinct clones identified in the 14 specimens that were analyzed, 8 were derived from a V1-69 VH gene segment, whereas the other 3 were derived from a V3-7 VH gene segment. In addition, the MESA clones also showed conserved amino acids sequence motifs in their third complementarity-determining regions (CDR3), some of which were encoded by N nucleotides. The marked VH gene restriction along with the similar CDR3 sequences suggests that MESA-associated clones even from different patients may bind the same or similar antigens and are selected for clonal expansion on that basis. The high rates of ongoing VH gene mutation observed in some of the cases futher suggest that the growth of early MESA clones is still dependent on antigen stimulation. In addition, our finding that different biopsies from the same patient may contain distinct clones indicates that some MESA-associated clones have not yet evolved to malignant lymphomas.

B-cell lymphoma of MALT type: a review with special emphasis on diagnostic and management problems of low-grade gastric tumours.

B-cell lymphoma of MALT type: a review with special emphasis on diagnostic and management problems of low-grade gastric tumours.

Detection of the Apoptosis-suppressing Oncoprotein bcl-2 in Salivary Gland Lymphoma

The bcl-2 proto-oncogene encodes an inner mitochondrial membrane protein that blocks apoptosis and programmed cell death in human lymphoid tissue. In this study a monospecific anti-human bcl-2 antibody that is reactive in formalin-fixed tissues was used with an avidin-biotin complex immunoperoxidase method to evaluate 41 cases of lymphoproliferative disorders of the salivary gland. The study cases were 26 primary salivary gland lymphomas (including 21 B-cell lymphomas four T-cell lymphomas and one true histiocytic lymphoma) and 15 cases of myoepithelial sialadenitis. Bcl-2 expression is restricted to the mantle zone and interfollicular lymphocytes around reactive germinal centers of myoepithelial sialadenitis. Seventeen of the 21 B-cell lymphomas were positive for bcl-2, and were composed of mucosa-associated lymphoid tissue (MALT), centrocytic, centroblastic-centrocytic and centroblastic lymphomas. Noticeably, all 11 cases of MALT lymphoma were bcl-2 positive. In contrast, staining for bcl-2 was present in only one of four cases of T-cell lymphomas and was negative in one true histiocytic lymphoma. The expression of bcl-2 protein was also investigated in the ductal systems and epimyoepithelial islands of salivary glands from patients with malignant lymphoma and myoepithelial sialadenitis. While salivary ducts in eight of 15 cases of myoepithelial sialadenitis immunostained for bcl-2, epimyoepithelial islands showed bcl-2 expression in only five cases of myoepithelial sialadenitis. We found that ductal cells in the salivary gland from patients with primary non-Hodgkin's lymphomas expressed bcl-2 protein. It was of interest that epimyoepithelial islands in all cases of MALT lymphoma displayed bcl-2 expression whereas other subtypes of B-cell lymphoma, T-cell lymphoma and true histiocytic lymphoma were invariably negative. These results indicate that bcl-2 is expressed in a wide variety of non-Hodgkin's lymphomas, especially when all 11 cases of MALT lymphoma are bcl-2 positive. Epimyoepithelial islands in MALT lymphoma express this oncoprotein, and their ability to induce bcl-2 synthesis resulted in the prevention of apoptosis and prolonged cell survival. Furthermore, the expression of bcl-2 protein in the lymphoma cells may be responsible for the induction of bcl-2 expression in the adjacent epimyoepithelial islands through a lymphocyte chemical mediator.

Benign and malignant lymphoid lesions of the salivary glands

Infiltration of the salivary glands by lymphocytes poses two major diagnostic problems: first, differentiating malignant lymphoma from reactive processes and second, separating autoimmune sialadenitis, which may progress to lymphoma from lesions lacking this implication. Non-autoimmune infiltrates characterize obstructive and infective diseases, several non-infective conditions and reactions to certain epithelial neoplasms. Autoimmunity plays a still poorly understood part in the pathogenesis of myoepithelial sialadenitis (MESA), a pathological entity frequently manifested as the clinical condition Sjogren's syndrome. A proportion of MESA develop malignant lymphoma of mucosa-associated lymphoid tissue (MALT) type, and recent studies have allowed the early stages in the evolution to malignancy to be recognized. If possible, MALT lymphoma should also be distinguished from nodal lymphomas presenting in intraparotid lymph nodes which are biologically different and usually carry a worse prognosis. Salivary lymphoepithelial cystic lesions are a heterologous group including Warthin's tumour, benign lymphoepithelial cyst, MESA with dilated ducts, cystic lymphoid hyperplasia of AIDS, MALT lymphoma with dilated ducts, cystic mucoepidermoid carcinoma with a lymphocytic response, and cystic metastases in intraparotid lymph nodes.

The Spectrum of Mucosa-Associated Lymphoid Tissue Lesions in Pediatric Patients Infected With HIV:A Clinicopathologic Study of Six Cases

Mucosa-associated lymphoid tissue (MALT) lesions in nonimmunocompromised individuals include reactive lymphoid proliferations and both low- and high-grade lymphoid neoplasms. These lesions occur at extranodal mucosal sites, such as the gastrointestinal tract, bronchus, salivary gland, and other locations. The spectrum of MALT lesions in children with HIV infection had not been previously described. In this study, six cases that demonstrated the spectrum of MALT lesions in pediatric patients, aged 28 months to 23 years, who had HIV infection were described. Half the patients acquired the infection perinatally, and half acquired it by transfusion. Mucosal sites of involvement included the salivary gland (4 patients), bronchiolar mucosa (2 patients), and oropharyngeal mucosa (1 patient). One patient had lesions in lung and oropharynx sequentially; all others had involvement of solitary sites. The histologic diagnoses included myoepithelial sialadenitis (MESA), MESA with low-grade MALT lymphoma, typical low-grade MALT lymphoma, diffuse large cell lymphoma (DLCL), and atypical pulmonary lymphoid hyperplasia and lymphoid interstitial pneumonitis complex. The two cases of high-grade DLCL were confined to mucosal sites (tonsil and parotid); in one of these patients, a previous biopsy specimen showed a MALT lesion with low-grade features. In two cases, quantitation of the Epstein-Barr virus (EBV) genome by the polymerase chain reaction showed a very high copy number in peripheral blood mononuclear cells but a low copy number in the MALT lesion, which suggested that MALT lesions may not be directly associated with EBV infection. Two patients who had high-grade tumors (DLCL) were successfully treated with chemotherapy and radiation therapy. The remaining patients, all of whom had low-grade MALT lesions, received either corticosteroids or alpha-interferon or no specific therapy; in all patients, the lesions followed an indolent clinical course. Clinicians and pathologists should be alert to the possibility that MALT lesions, including MALT lymphomas, may be present in children who have AIDS.

Analysis of immunoglobulin heavy chain gene rearrangement in myoepithelial sialadenitis by polymerase chain reaction.

Myoepithelial sialadenitis (MESA) can often be difficult to distinguish from low grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). The authors have previously studied a series of 25 patients with MESA and identified histologic and immunologic features predictive of extrasalivary lymphoma (ESL). The authors have now analyzed formalin-fixed, paraffin-embedded salivary gland tissue from 21 of these patients (and 1 new patient) for immunoglobulin heavy chain (IgH) gene rearrangement by a semi-nested polymerase chain reaction (PCR) technique to compare monoclonality by IgH PCR with clinical outcome (median follow-up 6.7 years, range 3 months-19.4 years) and the paraffin section immunophenotype. The PCR technique employed consensus primers from variable (FR3A) and joining regions (LJH, VLJH) of the IgH gene. A monoclonal PCR product was detected in 16 of 28 specimens from 13 of 22 patients. By Fisher's exact test, a monoclonal PCR pattern did not correlate (P > .05) with development of ESL, broad strands of monocytoid B-cells, plasma cell light chain restriction by immunoperoxidase, or CD43 coexpression on monocytoid B cells by immunoperoxidase. This study suggests that the majority of MESA lesions harbor monoclonal B-cell populations and that clonality does not predict progression to clinically overt lymphoma. Acquired salivary gland MALT, in the form of MESA, may progress to a process that is clonal but not necessarily malignant. Extranodal lymphoma develops in a minority of patients with this lesion.