are only 35% and 44%, respectively. emzl and other autoimmune diseases patients with an autoimmune disease other than hashimoto's thyroiditis also have an increased risk of developing an emzl in one or more tissue sites. for example, patients with systemic lupus erythematosus have a 7.5-fold increased risk of developing an emzl compared to the general population and at diagnosis of this development have a median age of 50 years and been diagnosed with systemic lupus erthyematosis for 6.7 to 17.8 years. patients with rheumatoid arthritis, immune thrombocytopenic purpura, and autoimmune hemolytic anemia are similarly susceptible to developing an emzl. while the exact reasons for these associations are unclear, it is generally considered that the chronic inflammation involved in each disease promotes the malignant behavior of b-cells and thereby the development of emzl. treatment of patients with an autoimmune disease complicated by emzl has usually involved the standard measures used to treat both the autoimmune disease and emzl. primary central nervous system primary emzl of the central nervous system is an extremely rare disorder. compared to other central nervous system lymphomas which are highly aggressive, primary emzl of the central nervous system is a non-aggressive, low-grade lymphoma. in a review of 70 published cases, the disease involved the proliferation of malignant marginal zone b-cells within the dura mater, i.e. thick membrane surrounding the brain and spinal cord, (56 cases), the brain or spinal parenchyma (6 cases), the brain's cavernous sinusn (4 cases), the brains choroid plexus (3 cases), inside brain (1 case), the cerebellopontine angle (2 cases), and the optic nerve (2 cases). patients (77% female; median age 55 years, ranging from 18 to 78 years) presented with various neurological signs and symptoms depending on the site of involvement. the most common presenting symptoms were headache (30 cases); seizures (22 cases); and visual changes (19 cases). less commonly, patients presented with paresthesias (i.e. abnormal skin sensations), motor deficits, and ataxias, memory failures, and dizziness. at the time of diagnosis, there was no evidence of emzl outside of the central nervous system. malignant cells were detected in the cerebrospinal fluid in 5 of the 19 cases tested for this. histologically, lesions in the disorder were typical of emzl in that they consisted of small to medium-sized b-cells that express cd19, cd20, and cd79a) but not cd10, cd23, or cyclin d1 marker proteins along with some plasma cells and a variable number of reactive t-cells. fifty percent of cases tested for trisomy of chromosome 3 were positive. treatment of localized disease consisted of surgery, radiotherapy, or a combination of both modalities whereas treatment of extensive central nervous system disease consisted of chemotherapy, including intrathecal chemotherapy, with or without surgery and/or radiotherapy. regardless of treatment regimen, primary central nervous system ezml has a good prognosis with complete response (cr) occurring in 77% of patients and 22% of patients alive with evidence of disease after 1–86 months of follow-up times. the values of systemic and intrathecal chemotherapy in treating the disease are unclear and require further study. primary breast primary emzl of the breast (also termed primary malt lymphoma of the breast) is an exceedingly rare disease. it usually presents as a palpable breast mass in an otherwise symptom-free patient. histopathological findings are typical for emzl: lesions consist of small- to medium-sized b cells, centrocyte-like b-cells, small lymphoid cells with some features of plasma cells or monocytes, and mature plasma cells with the lymphoid cells in these lesions expressing cd20 and cd79a but usually not cd10, cd43 or bcl6 marker proteins. moderate doses of local radiation therapy are recommended to treated localized emzl of the breast. this treatment has achieved overall survival rates of >90%. given these results and the high sensitivity of emzl to radiation therapy, mastectomy is not recommended and wide excision is not usually necessary to treat localized disease. for patients with disseminated disease, treatment options include watchful waiting and chemotherapy (typically employing a chop or chop-like regimen) with or without radiation therapy and/or excision. these approaches have attained complete disease remissions in 9 of 9 patients followed for 6–74 months and one death due to progressive disease in a patient followed for 107 months. other drugs used to treat the disease include rituximab, tamoxifen, and oxaliplatin. primary urinary tract primary urinary tract emzls of the urinary bladder and kidney are extremely rare but the most common forms of lymphoma that are found in these organs. they occur most commonly in middle aged females who have a history of chronic cystitis, i.e. inflammation of the bladder due to urinary tract infection or other causes. primary bladder presenting symptoms of primary bladder lymphoma include weight loss, fatigue, hematuria, dysuria, nocturia, urinary frequency, and pain in the abdomen and/or suprapubic area. however, this lymphoma commonly occurs as a disseminated disease involving other organs and tissues. radiological and cystoscopy examinations reveal one or more mucosal masses in, or diffuse thickening of, the bladder wall. the histopathology of these lesions is typical of emzl; they contain small lymphocytes some or many of which have plasma cell features with the malignant cells in these lesions typically expressing cd20 and pax-5 but not cd5 or cd10 marker proteins. the cells may also contain the t(11;18)(q21:q 21) translocation typical of ezml. treatment of primary bladder emzl depends on the extent of disease. localized disease should be confirmed using, e.g. positron emission tomography–computed tomography (i.e. pet/ct), magnetic resonance imaging (i.e. mri) of the pelvis area, and bone marrow examination. confirmed localized disease has been treated by surgery and radiotherapy with radiotherapy being the clearly preferred and most appropriate modality given this lymphoma's high sensitivity to radiation. however, surgical resection with resection of bladder tumor (i.e. turbt) may be the best treatment where fertility is of concern. disseminated and recurrent primary bladder emzl have been treated with systemic chemotherapy (usually a chop or chop + rituximab regimen. prognoses for treated localized and disseminated disease are good with long-term (e.g. up to 40 years) remissions reported for most patients with localized disease and (up to 10 years) for patients with disseminated disease. kidney kidney emzl (i.e. kidney malt lymphoma, renal emzl, or renal malt lymphoma) occurs primarily in individuals >50 years old but has been reported in individuals as young as 9 years. in slightly more than half of the reported cases, this lymphoma was localized to the kidney or detected in the kidney plus lymph nodes around the kidney, elsewhere in the retroperitonium, or along the abdominal aorta. these cases could therefore be regarded as primary kidney emzls. the remaining cases had widespread disease some of which appear related to primary salivary gland emzl, primary orbital emzl, helicobactor pylori-associated gastritis, systemic lupus erythematosus, or possibly an epstein–barr virus-associated lymphoproliferative disease, i.e. a lymphocyte-proliferating disease related to and thought to be caused by infection with this virus. patients may present with signs and symptoms of a kidney mass (e.g. low pack pain and/or abnormal kidney function as determined by elevation in serum creatinine). the best treatment for kidney emzl is unclear. reported cases have been subjected to nephrectomy and/or chemotherapy. primary gallbladder primary gallbladder emzl (i.e. extranodal marginal zone lymphoma of the gallbladder, primary malt lymphoma of the gall bladder) is an extremely rare disease with only 17 cases being reported in the literature as of 2017. presenting features in individuals (aged 31–84 years, median age 74, >60% females) with the disease are similar to those seen in other lymphomas and non-lymphomatous cancers of the gallbladder; these include pain in the upper right-side of the abdomen, nausea, vomiting, and in about two-thirds of cases, gallstoness. given these similarities as well as similarities in the laboratory, medical ultrasound, and x-ray findings of primary gallbladder emzl compared to other gallbladder cancers which account for >99% of bladder cancers, the diagnosis of primary gallbladder emzl has not yet been made pre-operatively. rather, its diagnosis has rested exclusively on examination of surgically removed gallbladders. the lesions in these gallbladders show infiltrates in the gland's submucosa that consist of small lymphocytes interspersed with lymphoepithelial lesions. the lymphocytes have marker protein profiles (e.g. cd20 and bcl-2 positive; cd5, cyclin d1 and cd10 negative) that are typical for emxl. cholecystectomy, i.e. surgical removal of the gallbladder, has produced remissions in all patients with only one recurrence over observation periods of 2 to 96 months. primary hepatic primary hepatic emzl (i.e. primary hepatic extranodal marginal zone b-cell lymphoma, primary hepatic mucosa-associated lymphoid tissue lymphoma, primary hepatic mucosa-associated lymphoma) is an extremely rare malignancy representing <3% of all primary lymphomas of the liver. only 47 cases of primary hepatic emzl were reported in the english literature as evaluated by a 2019 review. based on this review, individuals with primary hepatic emzl had concomitant liver disease ( principally hepatitis b viral hepatitis or hepatitis c viral hepatitis, less commonly, primary biliary cirrhosis or hepatocellular carcinoma, and, rarely, other liver diseases such as hepatitis a viral hepatitis. patients (median age 63 years, range 30–85 years) presented with no symptoms (~64% of cases) or symptoms (which may have been related to their other liver diseases) such as abdominal pain, generalized weakness, cough, elevations in their blood levels of liver enzymes, and/or evidence of one or more liver masses as detected by magnetic resonance imaging, computed tomography scans, or positron emission tomography. these presentations are virtually identical to those seen in other forms of liver cancer. accordingly, the diagnosis of primary hepatic emzl has been extremely hard to make without obtaining tissue by surgical methods. histological examination of involved liver tissues commonly showed diffuse infiltrations of small- to medium-sized atypical lymphocytes. these infiltrations, which may involve the liver's bile ducts, often contained lymphoepithelial lesions. immunohistochemistry testing of these tissues revealed lymphocytes that expressed cd20 and bcl-2 but not cd10 or cyclin d1. while optimal therapeutic strategies for this disease have not been established, primary hepatic emzl appears to be an indolent cancer. patients who underwent surgical resection with or without chemotherapy or rituximab treatment regimens and were observed over a median period of 31 months had mostly positive outcomes: 92% survived, 8% died of causes unrelated or only indirectly related to their cancer, and 11% had relapses. emzl associated with hepatitis c emzl occurs more frequently (~2.5-fold increased risk) in individuals who have hepatitis c virus-induced hepatitis. the lymphoma typically occurs 15–25 years (median times) after the viral infection and involves the skin (35% of cases), salivary glands (25%), orbital adnexa (15%) or, uncommonly, the stomach or other tissues. it is associated with type ii cryoglobulinemia, i.e. the circulation of an immune complex consisting of polyclonal igg, monoclonal igm, and hepatitis c viral rna. this immune complex causes signs and symptoms of vasculitis in 10% of cases. other signs and symptoms of the disorder include those associated with chronic hepatitis and the specific subtype of emzl. rarely emzl associated with hepatitis c virus infection presents as single or multiple soft, mobile sub-cutaneous nodules. this presentation occurs mainly in female (83% of cases) and elderly patients. patients with this disorder may have detectable levels of circulating hepatitis c virus. the histology of the lesions in emzl associated with hepatitis c virus infection is typical of emzl although the genomic abnormalities in the disorders malignant cells has not been well-defined beyond their expression of the t(14;18) chromosome translocation in a significant number of cases. treatment of this disease had relied on eradicating the virus using peginterferon-alfas, interferon-alpha-like drugs to mobilize the hosts' immune systems. this treatment cured the viral infection in ~50% and produced lymphoma remissions in <50% of cases. more recently, drugs (e.g. simeprevir, daclatasvir, sofosbuvir, and dasabuvir) that directly inhibit the virus's reproduction have cured the infection and achieved lymphoma responses in up to 100 and 73%, respectively, of patients with one year overall and progression-free survival rates of 98 and 75%, respectively. for patients whose lymphoma fails to respond to this therapy (~25% of cases), recommended treatments include rituximab or rituximab + a peginterferon-alfa. since chemotherapy regimens are highly toxic in patients with liver disease, they should be avoided, where possible, in treating emzl associated with hepatitis c virus infection. splenic marginal zone lymphoma main article: splenic marginal zone lymphoma splenic marginal zone lymphoma (smzl) is a low grade lymphoma in which malignant b-cells accumulate in the spleen, bone marrow, and, less