Testicular lymphoma

　　One, Etiology

　　Some patients have a history of testicular trauma, orchitis, or spermatic filariasis. It is extremely rare for the testes to not descend completely. However, the exact etiology of the disease is still unclear to this day.

　　Two, Pathogenesis

　　The size of testicular lymphoma varies greatly, often involving the epididymis, spermatic cord, and seminal vesicle, but rarely the tunica vaginalis and scrotal skin. Testicular lymphoma has different structures, with the majority of reported cases having intermediate to high grade, and diffuse large cell lymphoma being the most common type. Inexperienced pathologists are prone to misdiagnose primary testicular lymphoma as seminoma, and if the patient is elderly, it should be considered whether it is a lymphoma. The extent of the disease is the most important factor in diagnosis. The presence of lymph node metastasis (disease stage 2), especially massive lymph node enlargement, often has a poor prognosis. Other diagnostic factors include the size of the primary tumor (greater than 9cm), the appearance of systemic symptoms, and age over 65 years.

　　1. Gross specimen:

　　The gross specimen of testicular tumor mainly invades the testicular body, usually covered by a complete tunica albuginea of the testis. The seminal vesicle and epididymis are generally invaded. Gross specimen sections show that the tumor structure is arranged uniformly, the testis is diffusely invaded, often呈nodular, can be multiple, or single. It is often accompanied by hemorrhage and necrosis, usually gray, light yellow, light red, and brown.

　　2. Microscopic findings:

　　Testicular lymphoma is almost always non-Hodgkin's lymphoma, with Hodgkin's lymphoma being extremely rare. In addition to a few patients with nodular lymphoma in their histological structure, all testicular lymphomas are diffuse. However, due to the lack of unified classification criteria in early cases, the terms used were not uniform, with the majority being reticulum cell sarcoma, followed by lymphocytic type lymphoma. Later, most clinical reports adopted the Rappaport classification. In a group of 170 patients classified by this method, diffuse histiocytic type accounted for 76%; low differentiation lymphocytic type accounted for 14%; diffuse mixed cell type accounted for 3%; and other types accounted for 7%. The diffuse histiocytic type lymphoma in the Rappaport classification is actually a group of diseases that are very complex in immunology and morphology, and this subtype is basically classified as a poor prognosis lymphoma. Paladugu et al. reported 20 cases of diffuse histiocytic type lymphoma, of which 19 were large non-bridging cell type, which has a poor prognosis and is insensitive to chemotherapy compared to large cell lymphoma. Using the international working group classification method, 3 series of 69 testicular lymphomas, 47 were moderately malignant, 21 were highly malignant, and only 1 was lowly malignant.

　　1. The combined central nervous system lesions are mainly meninges, epidural space, and brain substance. Turner et al. reported 30 cases of testicular lymphoma, with 9 cases of central nervous system invasion, including 5 cases of meningeal invasion, 2 cases of epidural, 1 case of brain substance, and 1 case of both epidural space and meninges. Read reported 51 cases of testicular lymphoma, with 9 cases of central nervous system invasion, which is related to histological subtypes. Lymphoblasts and diffuse undifferentiated types are the most common, followed by diffuse histiocytic type and diffuse poorly differentiated lymphoma.

　　2. The opportunity for combined pulmonary infiltration is also common. Sussman et al. reported 37 cases of patients, with 9 cases of lung invasion. Read reported 51 cases of testicular lymphoma, with 8 cases of lung invasion. The incidence of lung invasion in autopsy results reported by different authors ranges from 50% to 86%.

　　Most patients present with painless testicular enlargement, dragging, which may last for several weeks to several months, occasionally for several years. Some patients may have pain, with a hard texture and smooth or nodular surface of the testicle. In the late stage, it may be accompanied by systemic symptoms such as anemia, weight loss, loss of appetite, fever, skin, and damage to the tonsils and surrounding tissues. In the terminal stage of the disease, multi-organ dissemination often occurs, including lymph nodes, bone marrow, spleen, skin, central nervous system, and lungs. Some may develop lymphocytic leukemia.

　　1. Ban smoking and drinking:The primary measure to prevent laryngeal cancer is to quit smoking, as smoking is the king of spicy and hot, and alcohol is the most damp and hot. Smoking and drinking are extremely harmful to the throat.

　　2. Light diet:All spices such as ginger, pepper, mustard, garlic, and other spicy and hot foods will harm the mucous membrane of the throat. These spicy and fried foods should be avoided, and more fruits and vegetables rich in vitamin C should be eaten.

　　3. Strengthening exercise:Participating in physical exercises regularly is also one of the measures to prevent laryngeal cancer, enhancing the body's defense ability.

　　Pathological and histological examination confirms the diagnosis of lymphoma. Complete blood count, bone marrow, liver and kidney function, and serum biochemistry tests are necessary. Due to the high chance of meningeal invasion, lumbar puncture cerebrospinal fluid cytology examination is also very necessary. Abdominal CT and lymphangiography are essential for accurate staging. If liver invasion is suspected, percutaneous liver biopsy and laparoscopic liver biopsy should be performed.

　　In terms of diet, attention should be paid to reasonable nutrition, and food should be as diverse as possible. Eat more high-protein, vitamin-rich, trace element-rich, low animal fat, easily digestible foods, as well as fresh fruits and vegetables. Avoid eating too much salty and spicy food, and do not eat overheated, cold, expired, or deteriorated food. Pay attention to avoiding staying up late and participating in more physical exercises to enhance the body's defense ability.

　　First, treatment

　　1. The initial treatment methods include radical orchiectomy, and some localized diseases can be cured by simple orchiectomy. Primary testicular lymphoma is considered a fatal disease. The 5-year survival rate is 16% to 50%, with a median survival time of 12 to 24 months. In the past, cases of treatment failure at a distant stage were common. For stage I and II patients, postoperative radiotherapy of paraaortic lymph nodes (35 Gy) should be performed after radical orchiectomy. After comprehensive treatment, the cure rate is 40% to 50% for stage I and 20% to 30% for stage II. Post-peritoneal lymph node radiotherapy can improve and control the growth of post-peritoneal lymph nodes, but has little impact on long-term survival. Chemotherapy can be selected from CHOP, COP, and COMP regimens. According to literature reports, the best results were achieved by Connors and his colleagues using three cycles of CHOP chemotherapy in 15 stage I and II patients, along with inguinal radiotherapy for stage I patients and radiotherapy of the inguinal, pelvic, and paraaortic lymph nodes for stage II patients. They observed that within 4 years, 93% of the patients achieved complete remission.

　　2. There are many records of cases with failure after simple orchiectomy followed by radiotherapy. The disease mainly develops outside the lymph nodes, including uncommon sites such as the skin, pleura, Waldeyer's ring, lung, liver, spleen, bone, and bone marrow, and 30% of patients have lesions in the central nervous system, including the brain and meninges. Recurrence can occur within 1 to 2 years after the initial treatment, especially in the central nervous system. Another failure is that 5% to 35% of patients may develop contralateral testicular lesions. In summary, chemotherapy based on doxorubicin can improve the survival rate of local testicular lymphoma, and patients at stage I do not need radiotherapy to achieve very good efficacy. Regional lymph node radiotherapy is often used for stage I and II patients. Low-dose radiotherapy (25 to 30 Gy in 10 to 15 days) can exclude the risk of contralateral testicular involvement. This regimen is effective in elderly patients and is recommended for all patients with primary testicular lymphoma, but its preventive effect on the central nervous system is still controversial. Connors and his colleagues did not observe any cases of treating central nervous system lesions with comprehensive methods, while Moller and his colleagues observed that systemic chemotherapy cannot prevent recurrence. Intrathecal therapy is ineffective because brain parenchyma involvement was found in failed cases, and the prevention of intrathecal chemotherapy and cranial radiotherapy is usually considered to have significant toxicity and is harmful to the elderly body.

　　3. Local disease management: Each patient should undergo orchiectomy + high ligation of the spermatic cord. After definite diagnosis, for patients at stage IIE and IIE, radiotherapy or radiotherapy combined with chemotherapy should be adopted. It was previously believed that radical orchiectomy was the main treatment for localized testicular lymphoma, but the results show that even in very early cases, approximately 40% of patients still die from systemic dissemination after surgery. Postoperative radiotherapy cannot reduce distant dissemination. Although radiotherapy is the main treatment method for patients at stage IIE and IIE, more than 50% of patients will still relapse after radiotherapy. Currently, it is considered that postoperative combined chemotherapy for patients at stage IIE and IIE should be routine. For patients who cannot tolerate or refuse chemotherapy, radiotherapy should be chosen. The radiation field should include the pelvic, inguinal, and para-aortic lymph nodes.

　　Fourth, patients in stages III to IV should receive combined chemotherapy, but the treatment results in the early years were very poor, with only a few patients surviving for more than 2 years. The efficacy is related to the intensity of treatment. In recent years, the complete remission rate (CR) of advanced high-risk lymphoma patients treated with strong combined chemotherapy has reached 23% to 87%, with 2-year survival rates and potential cure rates of 22% to 92%. These drugs also produce similar results in patients with advanced testicular lymphoma.

　　Fifth, Central nervous system and contralateral testis, due to the high risk of invasion of the contralateral testis and central nervous system in patients with testicular lymphoma, prophylactic treatment of the central nervous system should be considered. Since the early 1950s, Christie Hospital has adopted the method of prophylactic irradiation of the contralateral testis for all patients with testicular lymphoma, and no recurrence of the contralateral testis has been found. Therefore, it is believed that prophylactic testicular irradiation is successful. As for whether routine prophylactic treatment of the central nervous system should be performed, further prospective randomized studies are needed to determine, but some authors have reported that prophylactic intrathecal administration of MTX can reduce the possibility of recurrence of the central nervous system.

　　Second, Prognosis

　　The prognosis of testicular tumors is very poor, with a median survival time of 9.5 to 12 months. There are reports on the treatment results of testicular lymphoma, with a total 5-year survival rate of 12% (62/517). Most patients die of systemic dissemination within 2 years of diagnosis. Gowing reported on 128 patients with testicular lymphoma, with a mortality rate of 62% within 2 years, usually occurring within half a year after diagnosis.

　　Prognosis is closely related to clinical staging, Read analyzed the 5-year survival rate of 52 patients in stage I and II E to be 40%. None of the patients in stages III to IV survived for more than 5 years. In addition, pathological subtypes are also important factors affecting prognosis.