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 Sj?gren'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.     

Follicular lymphoma frequently originates in the salivary gland

The aim of the present study was to examine the clinicopathological presentations of follicular lymphomas (FL) of the salivary glands, as compared to mucosa-associated lymphoid tissue (MALT) lymphomas. A total of 27 primary salivary gland lymphomas were examined: 6 FL (five, grade 1; one, grade 2); 19 MALT lymphomas; and two diffuse large B-cell lymphomas. The FL patients ranged in age from 24 to 73 years, with a mean of 49 years, which was younger than that of MALT patients (mean: 64 years; P < 0.05). Four of the six FL arose from the submandibular gland, which was the origin of only five out of a total of 19 MALT lymphomas. One FL patient was in clinical stage (CS) IE, two in CS IIE, and two in CS III and IV. As regards the MALT lymphoma patients, 13 (68%) were in CS IE and five (26%) in CS IIE. None of the FL patients had clinical diagnosis of autoimmune disease but eight MALT lymphoma patients had autoimmune disease. The present study found a relatively high incidence of FL in the salivary glands. The observed differences in age of onset, background of autoimmune disease, and lesion site suggests that the pathogenesis of FL may differ from that of MALT lymphoma.     

Modulation of B cell maturation and migration to the thymus of SJL mice. B cell migration to the thymus.

The direct linkage of the B cell maturation process and infiltration of the thymus with mature B cells was studied in SJL mice. Phenotypically and functionally, B cells in the thymus of old SJL mice are mature B cells; IgM+, IgD+, Ly-1-, and evince a high proliferative response to lipopolysaccharide and a low one to dextran sulphate. Memory B cells can be found in the thymus of mice immunized with T-dependent or T-independent antigens. Chronic depletion and B cell maturation arrest induced by fractionated total lymphoid irradiation or by neonatal splenectomy eliminate B cells from the thymus and block their migration from the periphery to the thymus. When examined in adoptive transfer experiments, thymus B cells were found to possess a normal migration pattern and homing receptors; their migration pattern did not differ from that of lymph node or splenic B cells. It is evident, therefore, that the large number of normal functioning B cells in the thymus of SJL mice reflects a massive infiltration of the thymus by mature B cells from the periphery due to thymus dysfunction rather than to an abnormal in situ differentiation of intrathymic B cell precursors.     

Monocytoid B cell lymphoma.

The clinical, light microscopic, ultrastructural, immunocytochemical and cytogenetic features of a case of monocytoid B cell lymphoma were investigated. The tumour initially affected the cervical and supraclavicular nodes, but 33 months later affected the left parotid salivary gland. The patient had subclinical Sjögren''s syndrome. The neoplastic cells showed characteristic morphological features and had peri- and interfollicular distribution in the node. Immunocytochemically the tumour cells were L26, 4KB5, MB2, CD19, CD20, CD22 and IgM/kappa positive. Prominent plasmablastic plasmacytoid differentiation was present in the recurrent tumour, suggesting an origin from post-follicular B cells. The lymphoma cells showed unusual cytogenetic abnormalities.     

Osteoclastlike giant cell tumor of the salivary gland

Giant cell tumor of the salivary gland is extremely rare, with only 15 cases published in the English literature. The tumor characteristically contains a mixture of multinucleated giant cells, resembling osteoclasts of bone, and neoplastic mononuclear cells. In about half of the reported cases, there is an associated carcinomatous component. We are reporting an additional case of giant cell tumor of the parotid gland that was initially misinterpreted as an extraosseous osteosarcoma in the biopsy specimen. The histologic and immunohistochemical findings as well as a review of the literature with discussion of the histogenesis of this unusual neoplasm are presented.     

Primary T cell lymphoma of salivary gland: a report of a case and review of the literature

Lymphoma of the salivary gland accounts for 5% of cases of extranodal lymphoma and 10% of malignant salivary gland tumours. Most primary salivary gland lymphomas are B marginal zone lymphomas arising on a background of sialadenitis associated with autoimmune disorders such as Sjorgen's syndrome. Primary T cell lymphoma of the salivary gland is rare. This report describes a case of primary T cell lymphoma arising in the parotid gland of an elderly white man, which was notable for its striking resemblance to a B cell extranodal marginal zone lymphoma. Immunohistochemistry and gene rearrangement studies confirmed the clonal T cell nature of the tumour. There was no molecular evidence of Epstein-Barr virus (EBV) infection of neoplastic or surroundings cells. Only 14 cases of primary T cell lymphoma of the salivary glands have been recorded in the literature, most being from the Orient and having extremely variable prognosis. Those with a T/natural killer cell phenotype are associated with EBV infection. This case highlights the fact that T cell lymphoma in the salivary gland can mimic closely the morphological features of B cell extranodal marginal zone lymphoma.     

Primary carcinomas of the thymus gland.

Carcinomas of the thymus are now well recognized as distinctive but rare entities, and several clinicopathologic variants of such neoplasms have been described. These include keratinizing squamous cell carcinoma, nonkeratinizing squamous cell carcinoma, lymphoepithelioma-like carcinoma, neuroendocrine carcinoma, adenosquamous carcinoma, mucoepidermoid carcinoma, clear-cell carcinoma, papillary adenocarcinoma, adenocarcinoma not otherwise specified, basaloid carcinoma, and sarcomatoid carcinoma. The application of electron microscopy, immunohistology, and other adjunctive pathological techniques is effective in refining the differential diagnosis between primary thymic carcinoma (PTC) and several other histological simulators. However, the distinction between PTC and carcinomas that involve the thymic region by metastasis from other sites is a difficult one, and ultimately must be predicated on detailed clinical and radiographic information. Well-differentiated squamous carcinoma, low-grade mucoepidermoid carcinoma, and basaloid carcinoma of the thymus usually are associated with a favorable prognosis, but other variants are aggressive and require multimodality treatment approaches.     

Immunohistochemical localization of vitamin B12 R-binder in salivary gland tumors. Implications for cell differentiation

Vitamin B12 R-binder, a specific binding protein for vitamin B12, was studied immunohistochemically in normal and 106 neoplastic salivary gland tissues with a monoclonal antibody against vitamin B12 R-binder (R-binder). In normal salivary glands, R-binder localization was restricted to the ductal systems and to mucous acinar cells; serous acinar cells, myoepithelial cells and stromal connective tissues were consistently negative. Among salivary gland tumors, R-binder was present in 87% of pleomorphic adenomas, 100% of monomorphic adenomas, and 40% of adenoid cystic carcinomas; positivity was observed only on luminal surfaces of small ductular elements, indicating that the components closely related to ductal differentiation were rather small in population. R-binder could be detected both in lacunar and non-lacunar cells within chondroid areas of pleomorphic adenomas, suggesting the possibility that chondroid regions arise from metaplastic changes in ductal epithelial cells. In mucoepidermoid tumors, mucous cells and focal squamous cells exhibited cytoplasmic staining. The staining pattern for R-binder in epithelial components of adenolymphomas showed close similarities to those found in normal large excretory ducts. Two acinic cell tumors and one case each of myoepithelioma and malignant myoepithelioma exhibited negative reactivity for R-binder, showing that these neoplasms are solely composed of tumor cells without the characteristics of ductular differentiation. The immunohistochemical examination of salivary gland tumors, employing a monoclonal anti-R-binder antibody, may have some implications for cellular heterogeneity and differentiation in various tumors.     

Myoepithelial cell activation in the submaxillary salivary gland

1. Pressure in the duct of the submaxillary gland of the cat was recorded under chloralose anaesthesia. Single pulses applied to the parasympathetic nerve caused a pressure rise.2. Salivation was just detectable in about half of the animals when an open tube was connected to the duct and single pulses applied to the nerve. Applying a back pressure of 1-4 mm Hg renders the duct less distensible and under these circumstances secretion of 1-3 mul. fluid was always seen. An alternative method of detecting salivation based on the pressure record itself also showed that salivation occurred in response to the stimulus and that salivation was responsible for the pressure rise observed.3. Single pulses applied to the cervical sympathetic trunk produced a small fall in pressure. In a short series of pulses this was followed by a slow rise which then slowly decayed. It was tentatively concluded that the initial fall was secondary to the accompanying vasoconstriction but the subsequent effects were due to myoepithelial cell contraction.4. Close arterial injection of bradykinin caused a pressure rise which could best be explained by myoepithelial cell contraction.5. It is concluded that the myoepithelial cells of the submaxillary gland of the cat do not receive a parasympathetic motor innervation but it is probable that they are innervated by the sympathetic nervous system and contract in the presence of bradykinin.     

Myoepithelial cell markers in salivary gland neoplasms

We compared the immunoexpression of 5 myoepithelial cell (MEC) markers (alpha-smooth-muscle actin, calponin, h-caldesmon, vimentin, and S-100-protein) using 16 pleomorphic adenomas (PA), 15 adenoid cystic carcinomas (ACC), and 3 epithelial-myoepithelial carcinomas (EMC) of salivary glands. The alpha-smooth-muscle actin was useful for identification of MECs, especially in cribriform and tubular ACC, followed by EMC. Calponin was similar to alpha-smooth-muscle actin, except for polygonal and plasmacytoid cells of PA and for solid ACC, which showed alpha-smooth-muscle actin negative and calponin positive. H-caldesmon was negative. Vimentin immunostained all MEC types, and was negative in luminal cells. S-100 protein was expressed both in the nuclei and cytoplasm of MECs and luminal cells, especially in PA. The best way to identify MEC is using alpha-smooth-muscle actin or calponin, plus vimentin, since in tumors MECs are hardly ever fully differentiated.     

B cell signet-ring cell lymphoma of bone marrow.

A case of signet-ring cell lymphoma affecting the bone marrow and diagnosed by bone marrow trephine biopsy is reported. Normal marrow was replaced totally by cells with large central vacuoles, many of which displaced the nucleus to the periphery of the cell, imparting a signet-ring appearance. Initially, the favoured morphological diagnosis was metastatic signet-ring adenocarcinoma, but on immunocytochemistry the tumour cells were strongly positive for CD45 (leucocyte common antigen) and the B cell marker CD20 (L26). Electron microscopy revealed electron-lucent vacuoles with no discernable internal structure. The tumour was classified as a high grade centroblastic lymphoma using the upgraded Kiel classification. Despite chemotherapeutic treatment, the patient died during an episode of septicaemic shock within two months of presentation.     

"Clear cell" oncocytoma of salivary gland

For the most part, clear cell neoplasms of the salivary glands are adenocarcinomas of at least low-grade malignant potential. However, a rare benign clear cell tumor of major salivary glands can be distinguished as a histologic variant of oncocytoma and oncocytosis. Ten such cases have been identified in the files of the Armed Forces Institute of Pathology (Washington, DC). Eight patients were women, and nine of the lesions involved the parotid gland. All of the patients were middle-aged or older adults. The light-microscopic morphology and the phosphotungstic acid-hematoxylin (PTAH), PAS, and mucicarmine staining patterns were consistent with oncocytoma and oncocytosis. Transitions from typical eosinophilic oncocytes to clear cells were evident. Electron microscopy and histochemistry demonstrated that the clear cytoplasm seen by light microscopy was primarily due to artifact and intracytoplasmic glycogen. Mitochondria were the preponderant cytoplasmic organelles. Two patients were known to have experienced recurrent lesions.     

Immunohistochemical characterization of basal cell adenomas of the salivary gland

Seven cases of basal cell adenomas of the salivary gland were analyzed by immunohistochemical methods with a broad panel of routinely used antibodies. Histologically the epithelial elements were classified as tubuloglandular, trabecular and solid patterns. The authors' results indicated the following: 1) The duct lining cells of tubuloglandular and trabecular patterns have distinct epithelial features with cytokeratins (KL 1, PKK 1, *PKK 2 and PKK 3), alpha-one-antichymotrypsin (alpha 1-ACT), carcinoembryonic antigen (CEA) and S-100 alpha subunit positivity. 2) The basaloid cells in the trabecular and solid patterns expressed two immunophenotypes: one had actin, neuron-specific enolase (NSE), S-100 protein and S-100 beta subunit patterns typical of myoepithelial cells in normal glands. The other basaloid cells had vimentin and S-100 protein patterns. The former cell type could be found in 4 of 7 cases and the latter was found in 7 cases. This represents a minor participation of the myoepithelial cells in the basal cell adenoma. 3) The basement membrane and stromal connective tissue around the neoplastic cells were positive for alpha-one-antitrypsin (alpha 1-AT). This antibody is a good marker in identifying the basement membrane-like material.     

Low-grade B cell lymphoma of mucosa-associated lymphoid tissue in the thymus of a patient with rheumatoid arthritis

The majority of thymlc lymphomas are either lymphoblastic lymphoma, large B cell lymphoma or Hodgkin's disease, and other types of non-Hodgkin lymphoma are rare. A case of low-grade B cell lymphoma of mucosa-associated lymphoid tissue (MALT) In the thymus is reported. A 55-year-old Japanese female with a history of rheumatoid arthritis (RA) complained of back pain. A mediastinal tumor was identified by computerized tomography and magnetic resonance imaging, and the thymus was resected through median sternotomy. The solid and nodular tumor had several small satellite extensions and was completely confined to within the thymus. Hlstologically, monotonous medium-sized centrocyte-like cells occupied the medulla of the thymus and Infiltrated Hassan's corpuscles (lymphoepithellal lesions). Immunohistochemically, tumor cells were positive for CD20 and CD79a. IgA and kappa light chain restriction were also found in plasmacytoid cells in the tumor. Clonal rearrangement of the immunoglobulin heavy chain gene was demonstrated by polymerase chain reaction. This case was diagnosed as MALT-type low-grade B cell lymphoma In the thymus. This is the first report of low-grade B cell lymphoma In the thymus associated with RA. As autoimmune diseases are known to be associated with lymphoid neoplasms, It is suggested that the RA played an Important role in the development of malignant lymphoma in this case.