Patients with AIDS often have a combination of opportunistic infections and tumors, such as Mycobacterium bovis infection, Penicillium marneffei infection, cryptococcal infection, lymphoma, Kaposi’s sarcoma, etc. These opportunistic infections or tumors may manifest on the body surface as enlarged lymph nodes, rashes, local skin swellings, etc. The “gold standard” for the diagnosis of opportunistic infections and tumors is pathogenic culture, and the “gold standard” for the diagnosis of superficial tumors and localized masses is biopsy pathology. However, pathogenic culture takes a long time, and biopsy of surface masses is difficult for patients with AIDS because of their low immunity, difficult wound healing, and easy co-infection.
Fine Needle Aspiration (FNA) is a simpler and less contraindicated method for puncturing surface lymph nodes, rashes, and local skin swellings, and can be used as an alternative diagnostic method to histopathological testing. The method is less invasive, the wound heals easily, and the pathological tissues obtained can be cultured for opportunistic infection pathogens, and cytopathological examination can be performed, which is more helpful for the diagnosis of AIDS opportunistic infections and tumors.
In this study, we analyzed the accuracy, sensitivity, specificity, and negative/positive predictive values of needle aspiration cytology pathology of body surface lymph nodes and skin mucosal swellings in AIDS patients, as well as the common disease spectrum of AIDS needle aspiration cytology pathology.
Methods.
1. Materials: AIDS diagnostic criteria were referred to the 2006 AIDS Diagnostic Guidelines developed by the AIDS Group of the Chinese Medical Association’s Division of Infectious Diseases; we collected a total of 85 needle aspiration cytology pathology specimens from 69 AIDS patients from March 2009 to September 2011, and each patient signed an informed consent form before completing the puncture. Of these, 77 were lymph node specimens, 3 were arm swellings, 2 were breast swellings, and 1 each was a skin, oral mucosa, and scapular swelling specimen. All AIDS patients were cultured for opportunistic infection pathogens and treated according to the results of needle aspiration pathology and pathogen culture, and patients were followed up after treatment.
2. Method: The specimens were collected by a pathologist using a “friendly fine needle puncture device” (10 ml syringe with 0.7-0.8 mm outer diameter injection needle) after local sterilization and stabbing into the target site with a pen-held negative pressure needle aspiration specimen. The specimen is aspirated to complete 3-6 smears, fixed in 95% ethanol, and stained with HE and PAS; if the patient is diagnosed with lymphoma, immunohistochemical testing is performed.
3.Pathogenic culture, clinical treatment effect and follow-up observation: all AIDS patients were cultured for opportunistic infection pathogens and treated according to needle aspiration pathology and pathogenic culture results, and patients were followed up after treatment; the correctness of needle aspiration cytopathology results was judged according to pathogenic results, treatment effectiveness and follow-up.
4. Statistical analysis: The accuracy, sensitivity, specificity, negative predictive value, positive predictive value of needle aspiration cytopathology and its 95% confidence interval of these indicators were analyzed by using statistical analysis software SPSS12.0.
Results.
Analysis of the precision of needle aspiration pathology in patients with AIDS.
We performed 85 needle aspiration cytology biopsies in 69 patients with AIDS, mainly puncturing the enlarged lymph nodes of patients with AIDS, mainly the cervical lymph nodes, which accounted for 65 specimens, followed by inguinal, supraclavicular and axillary lymph nodes; a small number of needle aspiration biopsies of body surface masses, skin and mucosa were also performed.
The pathology reports of 85 biopsy specimens were completed independently by two pathologists in our pathology department, of which 51 specimens were found to be positive, i.e., those with opportunistic infections or tumors such as branchial mycobacteria, lymphoma cells, fungal infections or bacterial inflammation; 19 specimens were not found to be positive, only tissue hyperplasia was found; 5 specimens were suspected to be positive, therefore, the pathological diagnostic yield of needle aspiration biopsy ( The diagnostic yield of needle aspiration biopsy was 88.2%.
Using clinical pathogenic culture, clinical efficacy and follow-up as the diagnostic “gold standard”, and comparing with the results of needle aspiration cytopathology, we found that one of the positive and one of the suspicious positive specimens was a false positive; the other patients with suspicious and positive results were treated with opportunistic infection or anti-tumor therapy according to the pathological results, and their disease could be controlled. These pathological diagnoses were consistent with the clinical pathogenic culture, clinical outcome and follow-up results.
In addition, 10 out of 85 biopsy specimens were diagnosed unsatisfactorily, i.e., the pathological results were negative but inconsistent with the clinical pathogenic culture, clinical efficacy and follow-up results, and only 1 case was found to be negative by re-needle aspiration biopsy and clinical follow-up, and 9 cases were found to be false negative, i.e., 74 out of 85 biopsy specimens were diagnosed clearly, suggesting that the accuracy of the pathological diagnosis by needle aspiration biopsy was 87.1%.
Sensitivity refers to the percentage of specimens with actual disease that were correctly judged as having disease according to the diagnostic criteria of needle aspiration pathology, and this study showed that 54 specimens were diagnosed as true positive by needle aspiration pathology and 9 were false negative, suggesting a sensitivity of 85.7%.
Specificity refers to the percentage of specimens that are actually disease-free and are correctly judged as disease-free according to the diagnostic criteria of needle aspiration pathology.
The positive predictive value is how likely it is to have the disease when the pathology of needle aspiration biopsy is positive; we found 54 diagnostic positive specimens and 2 false positive specimens, with a positive predictive value of 96.4% (95% confidence interval 0.92-1.00); the negative predictive value is how likely it is not to have the disease when the pathology of needle aspiration biopsy is negative; we found 20 diagnostic negative specimens and 9 false We found 20 diagnostic negative specimens and 9 false negative specimens, with a negative predictive value of 69% (95% confidence interval of 0.52-0.86).
Disease spectrum and pathological features of needle aspiration pathology in patients with AIDS.
Pathological findings and final clinical follow-up revealed opportunistic infections as the main disease type in AIDS needle aspiration pathology, with lymph node tuberculosis being the most common, in 23 patients; Mycobacterium avium accounted for 6, suggesting that Mycobacterium avium is the main cause of lymph node enlargement in AIDS patients; lymph node tuberculosis showed microscopic signs of caseous necrosis and tuberculous granuloma with antacid staining (+) and long bacilli visible in phagocytes. Mycobacterium avium infection was seen as focal tissue hyperplasia with granulomatous lesions, and red short bacilli were seen in the cytoplasm on antacid staining.
In this study, two patients with lymph node infection with Cryptococcus spp. were found to have microscopically disrupted lymph node structure with granuloma structure, phagocytosis with large number of round budding spores, positive hematoxylin-eosin staining and PAS staining; the lymph node pathological structure and pathogenic findings were consistent. This study also found Penicillium marneffei infection in the lymph nodes of five patients, with rasping bodies visible in the lesions and transverse septa in the middle.
In addition, lymphoma is a common complication of AIDS, with diffuse large B lymphoma diagnosed in five patients and Burkitt’s lymphoma in four patients. Diffuse large B-cell lymphoma fine needle aspiration cytology revealed a single heterogeneous large lymphocyte, immunohistochemistry suggested tumor cells CK (-), Syn (-), CD20 (+), CD3 (-), hexonium silver (-), antacid (-).Burkitt lymphoma cytology pathology revealed proliferating active lymphocytes, mostly activated mother cells, fine chromatin, common nuclear schwannoma, immunohistochemical findings suggesting Bcl-6(+), CD10(+), CD20(+), CD3(-), Ki-67(+), Mum-1(-).
Discussion.
In our study, we found that the pathological accuracy, specificity and sensitivity of needle aspiration cytology biopsy of body surface lymph nodes, masses, skin and mucosa in patients with AIDS were high.Meera et al. reported that the specificity and sensitivity of needle aspiration cytopathology of body surface lymph nodes were 96% and 89.8%, respectively, in the Indian population; Sudarat et al. reported that the accuracy, specificity and sensitivity of needle aspiration cytopathology of breast masses in the Thai population were In our study, the accuracy, specificity and sensitivity of needle aspiration cytology biopsies of surface lymph nodes, masses, skin and mucosa of AIDS patients were 87.1%, 85.7% and 90.9%, respectively, which were similar to those reported overseas.
We found that among 85 needle aspiration pathology specimens, 75 had clear diagnostic results, so the diagnostic yield was 88.2%; in addition, 10 biopsy specimens had unsatisfactory diagnoses, i.e., negative pathology results, but inconsistent with the pathogenic results, clinical manifestations, treatment results and follow-up results. The pathological false negatives of needle aspiration biopsy were caused by the following factors: one possibility was the inexperience of the needle aspiration biopsy physician; secondly, the blind puncture technique was used, and ultrasound guidance was not used to position the puncture; thirdly, the diameter of the lymph node itself was less than 1.5 cm, which made the puncture difficult; fourthly, less tissue was obtained from each puncture, and for the same lymph node only one puncture was performed at a time. Fourth, the number of punctures was low, and only 1-2 punctures were performed each time for the same lymph node, which resulted in less positive tissue; some reports showed that at least 5-6 punctures, up to 10, were required to obtain a positive specimen for endoscopic ultrasound-guided needle aspiration biopsy, so increasing the number of punctures could improve the positive rate of needle aspiration cytopathology.
The positive predictive value is how likely it is to have the disease if the needle aspiration biopsy pathology is positive; the negative predictive value is how likely it is not to have the disease if the needle aspiration biopsy pathology is negative. We found that among 85 needle aspiration pathology specimens, there were only 2 false positive results, and the positive predictive value of pathology was 96.4%, suggesting that the positive predictive value of needle aspiration pathology in AIDS patients is high, and the pathology is reliable when the needle aspiration pathology is positive; however, we found 9 false negative results, and the negative predictive value of pathology was 69%, suggesting that the negative predictive value of needle aspiration pathology in AIDS patients is low when Patients with negative needle aspiration pathology results should be alerted to the appearance of false negatives and should improve needle aspiration biopsy pathology again, or even improve tissue biopsy to further clarify the diagnosis.
Our study shows that needle aspiration cytology in AIDS patients is mainly biopsy of body surface lymph nodes, mainly in the neck, supraclavicular, axillary and inguinal areas, and the pathological results are mainly branching bacilli infections, the common ones in China are Mycobacterium tuberculosis and Mycobacterium avium infections, we diagnosed 23 cases of lymph node tuberculosis and 6 cases of Mycobacterium avium infections in lymph nodes, both of which had positive pathological antacid staining, and the branching bacilli were intracellular. Mycobacterium tuberculosis showed long rod-shaped bacilli under intracellular staining microscopy, while Mycobacterium avium showed short rod-shaped bacilli under intracellular staining microscopy, which is important for differentiating Mycobacterium tuberculosis from Mycobacterium avium infection and guiding clinical treatment.
Cryptococcal infection is a common opportunistic infection in patients with AIDS, and in this study, two patients were found to have lymph node infection with Cryptococcus. Microscopic destruction of lymph node structure, granuloma structure, and phagocytosis with a large number of round budding spores were seen. Hematoxylin-eosin staining and PAS staining were helpful for diagnosis, but to confirm the diagnosis of cryptococcal infection, fungal culture or cryptococcal antigen detection was required.
In our study, Penicillium marneffei infection was found in the lymph nodes of 5 patients, and the lesions were seen to have a salami-like body with a central transverse septum; however, Penicillium marneffei is easily confused with Histoplasma capsulatum, which has budding spores and no salami-like morphology or transverse septum; in addition, fungal pathogenic culture helps to differentiate.
Our study showed 5 cases of diffuse large B lymphoma and 4 cases of Burkitt’s lymphoma by needle aspiration cytology pathology. The diagnosis of malignant lymphoma is extremely difficult and should be differentiated firstly between lymphoma or lymphatic reactive hyperplasia or lymphadenitis, and secondly between Hodgkin’s lymphoma and non-Hodgkin’s lymphoma. Diffuse large B lymphoma and Burkitt’s lymphoma are B-cell non-Hodgkin’s lymphoma, and the former is moderately malignant while the latter is highly malignant. Immunohistochemical tests for CD10 and Ki67 against B-cell lymphoma are helpful for differential diagnosis; the proportion of CD20 (+) and Ki67 positivity in diffuse large B lymphoma is 60-70%, and the proportion of CD10 (+) and Ki67 positivity in Burkitt’s lymphoma greater than 95%.
In conclusion, our study found that the pathological accuracy, specificity, sensitivity and positive predictive value of AIDS needle aspiration cytology biopsy are high, which is helpful for the diagnosis of AIDS opportunistic infections and tumors; however, the negative predictive value is low, and we should be alert to the occurrence of false-negative results.