(i) Implementation of malignant lymphoma staging
Necessary diagnostic procedures.
(i) The specimen needs to meet the requirements for a diagnosis by an experienced pathologist.
(ii) Detailed history: record the presence or absence of symptoms, the presence and duration of fever, unexplained night sweats and the extent of night sweats, and the presence or absence of skin pruritus and weight loss.
③ Careful and comprehensive physical examination: detailed examination of superficial lymph nodes, including submandibular, retrooccipital, preauricular, cervical, upper and lower clavicle, axillary, supraclavicular, iliac fossa, inguinal, and lunar fossa lymph nodes; pharyngeal lymphatic ring must be examined; in the abdomen, note any enlargement of liver and spleen and any abdominal mass.
④ Necessary laboratory tests: blood routine, blood sedimentation, bone marrow aspiration or biopsy; serum alkaline phosphatase, lactate dehydrogenase; liver and kidney function tests.
⑤ X-ray examinations: frontal and lateral lung films, CT of chest or abdomen, bilateral lymphography of lower limbs.
Selective diagnostic steps.
① whole lung tomography for abnormalities in conventional lung films and enlarged mediastinal hilar lymph nodes.
②Bone scan.
③67Ga scan.
④hepatic biopsy.
⑤ lumbar puncture and cerebrospinal fluid examination.
Hodgkin’s disease without hilar lymph node enlargement is less likely to have pulmonary invasion. When there is hilar or mediastinal lymph node invasion, conventional lung films are negative, but whole lung tomography has parenchymal invasion in about 3.5%.
In non-Hodgkin’s lymphoma, 15%-25% have enlarged mediastinal lymph nodes and parenchymal invasion accounts for 3%-6%, commonly in the diffuse type. 8%-10% have pleural fluid, plasma chylous effusion or leakage fluid, but no malignant cells do not change the pathological stage, lung films are normal, and less than 2% have pulmonary infiltration on whole-lung tomography; whole-lung tomography should be performed when there is hilar or mediastinal lymph node enlargement.
Radionuclide bone scan is more sensitive than bone x-ray, and bone scan shows increased nuclide uptake in the lesion area, and diffuse histiocytic lymphoma often has bone infiltration.
(ii) Bone marrow examination
The elevated serum alkaline phosphatase often indicates bone marrow invasion. In non-Hodgkin’s lymphoma, the incidence of bone marrow invasion is related to the pathological subtype, and the incidence of bone marrow invasion in lymphocytic lymphoma can be as high as 40%-90%, while the incidence of diffuse histiocytic lymphoma is only 5%-15%. Due to the clinical importance of bone marrow examination and the focal nature of metastases, more than one puncture and/or biopsy is often required. For two or more positive bone marrow tests, a second biopsy increases the rate of positivity by 5-10%, and a bone marrow biopsy will result in a revised stage IV in 1/4 of the patients, mainly in stage III patients with poorly differentiated follicular lymphatic pathology and well differentiated diffuse lymphocytes. Only 37% of patients with bone marrow invasion have blood abnormalities, and 15% of non-Hodgkin’s lymphoma have malignant cells in the peripheral blood, mainly in poorly differentiated lymphocytic lymphoma.
(iii) Lymphography of the lower extremities
Most of the lower limb lymphography is used to find out whether the pelvic and para-aortic lymph nodes are invaded by the tumor. Lower limb lymphography is often used as a routine test in malignant lymphoma.
Lower extremity lymphography is used in malignant lymphoma for the following purposes.
① mainly for the staging of malignant lymphoma, and lymphangiography of the lower extremities is an important part of the clinical staging of lymphoma.
② To judge the efficacy of radiation therapy.
③ To detect disease recurrence.
Lymphography is currently the only diagnostic X-ray method that can observe the internal structure of lymph nodes. The contrast agent can be retained in the body wind for 9 months to 1 year, and the film can be repeated to observe the efficacy of treatment.
(iv) Staged dissection
Staged dissection includes.
(i) wedge-shaped excisional biopsy of the liver margin and needle aspiration biopsy of the deeper part of the liver.
② bone marrow biopsy.
③ splenectomy (including splenic hilar lymph nodes) and understanding of splenic involvement and biopsy of suspected lymph nodes in the para-aortic, celiac artery, splenic hilar and iliac fossa. Dissection helps to understand the extent of the lesion comprehensively and make the staging more correct so that a reasonable treatment plan can be formulated. In recent years, due to the widespread use of B-ultrasound and CT, dissection is performed only when the results of the exploration will change the treatment plan.
(V) CT examination
CT scan can detect lymph node groups that cannot be detected by lymph node imaging of the lower extremities, such as lymph nodes in the mesentery, behind the foot of the diaphragm, peripancreatic, hepatic hilar, abdominal artery, etc. CT can also detect lesions of organs, especially renal parenchymal lesions, which are more likely to detect direct extra-nodal invasion. However, CT scan also has limitations. Firstly, the size of lymph nodes is used to determine the presence or absence of lesions, and internal structures cannot be observed, so a portion of reactive hyperplasia is often misdiagnosed as positive as well; secondly, pelvic lymph nodes shown by CT are not as clear as lymph node imaging of lower extremities.
CT scan should be considered first if possible because non-Hodgkin’s lymphoma often invades lymph node areas and organs that cannot be visualized by lymphography, and CT has a high false-negative rate for spleen diagnosis. As for CT of the chest, it is sometimes beneficial for the diagnosis of the foot of the diaphragm, mediastinal lesions, and enlarged lymph nodes such as paratracheal, hilar, and para-aortic windows.
(vi) Ultrasound examination
Ultrasonography can detect lymph nodes >2 cm in diameter, but it cannot identify whether the enlarged lymph nodes are tumor invasion or reactive hyperplasia or chronic inflammation. Ultrasonography can detect enlarged liver and spleen and obvious tumor nodules in the liver and spleen, but when the liver and spleen are normal in size but have diffuse infiltration, it cannot confirm liver and spleen invasion.
(vii) Liver biopsy
Liver invasion is more common in non-Hodgkin’s lymphoma than in Hodgkin’s disease. In non-Hodgkin’s lymphoma, small lymphocytes and small lytic cells are more likely to have liver invasion than large lytic cells. Percutaneous liver puncture reveals liver invasion in about 20% of patients, and a negative liver puncture followed by laparoscopy can increase the positive rate by 10%. Laparoscopy allows for multiple needle aspiration biopsies under direct visualization. In addition, laparoscopy can also visualize lesions in the stomach, mesentery, spleen and splenic hilum, with fewer complications than dissection, and the diagnostic rate of liver invasion is no less than that of dissection.
(viii) 67Ga scan
The results of 67Ga scan are influenced by the anatomical site and pathology. Most reported 67Ga scans are highly sensitive for mediastinal lesions, with a sensitivity of 80%-95%, and for retroperitoneal lymph nodes, with a sensitivity of 10%-60%. 67Ga scans are valuable for the examination of histiocytic lymphomas, with 60%-80% of lymph node invasion being detected. The detection rate for better differentiated lymphocytic tumors is only 50%. Lymph nodes in the iliac fossa are difficult to detect because of 67Ga accumulation in the cecum and sigmoid colon.