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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 6  |  Issue : 1  |  Page : 45-50

Cytomorphology of lymphadenopathy with a report on patterns of tuberculous lymphadenitis in a resource-limited setting


1 Department of Pathology, Indira Gandhi Government General Hospital and Post Graduate Institute, Puducherry, India
2 Department of Radiology, Indira Gandhi Government General Hospital and Post Graduate Institute, Puducherry, India

Date of Submission17-Mar-2020
Date of Decision16-Apr-2020
Date of Acceptance08-May-2020
Date of Web Publication20-Jul-2020

Correspondence Address:
Bakiarathana Anand
20, First Floor, Thirumurugan Street, Kamaraj Nagar, Puducherry - 605 011
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrsm.jcrsm_16_20

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  Abstract 


Context: Lymphadenopathy is one of most common clinical presentations, for which fine-needle aspiration (FNA) is indicated as the first-line investigation since it is a reliable, rapid, simple, cost-effective procedure done in the outpatient department.
Aims: The study was performed to assess the various cytomorphological patterns of the lymph node aspirates in patients presenting with peripheral lymphadenopathy.
Subjects and Methods: The prospective study included 81 patients with complaints of peripheral lymphadenopathy on whom FNA was done in the Department of Pathology at our hospital. The smears were analyzed and categorized according to their cytomorphological patterns.
Results: Of 81 patients, 30 were male and 51 were female. The male:female ratio was 1:1.7. The age of the patients ranged from 3 to 83 years, with a mean age of 35.2 years. Reactive lymphadenitis (48.15%) was the most common lesion followed by tuberculous lymphadenitis (33.33%). Acid–fast bacilli (AFB) positivity was noted in 13 out of 27 cases (48.15%) with tuberculous lymphadenitis. The cases of tuberculous lymphadenitis were further divided into three groups based on cytomorphology, of which Group 2 lesions (epithelioid granulomas with necrosis) were most common and Group 1 lesions (epithelioid granulomas without necrosis) were least reported. Group 3 lesions (necrosis without epithelioid granulomas) were all positive for AFB. There were nine cases (11.11%) of acute suppurative lymphadenitis and six cases (7.41%) of metastatic squamous cell carcinoma to the lymph nodes.
Conclusions: FNA is an ideal tool which can be used as a basic investigation for the evaluation of lymphadenopathy. Reactive lymphadenitis followed by tuberculosis was the major cause of lymph node enlargement in our setup. Epithelioid granulomas with or without necrosis and/or AFB positivity on the cytological smears and with associated clinical symptoms should be considered as tuberculosis in our clinical setup unless proven otherwise.

Keywords: Cytomorphological patterns, fine-needle aspiration, lymphadenopathy, reactive lymphadenitis, tuberculosis


How to cite this article:
Anand B, Mariaselvam A. Cytomorphology of lymphadenopathy with a report on patterns of tuberculous lymphadenitis in a resource-limited setting. J Curr Res Sci Med 2020;6:45-50

How to cite this URL:
Anand B, Mariaselvam A. Cytomorphology of lymphadenopathy with a report on patterns of tuberculous lymphadenitis in a resource-limited setting. J Curr Res Sci Med [serial online] 2020 [cited 2020 Aug 7];6:45-50. Available from: http://www.jcrsmed.org/text.asp?2020/6/1/45/290242




  Introduction Top


Lymphadenopathy is the most common clinical presentation with variable etiologies, for which patients seek medical attention. It may be an incidental finding and/or primary or secondary manifestation of underlying diseases, which may be neoplastic or nonneoplastic. The morphological changes depend on the inciting stimulus and the intensity of the response.[1]

Fine-needle aspiration (FNA) serves as an important tool in the evaluation of peripheral lymphadenopathy, and it can be used as a safe alternative to excision biopsy. It is indicated as a first line of investigation in patients since it is a reliable, rapid, simple, cost-effective procedure done in the outpatient department.[2],[3] Cytomorphological study of the smears is used to determine whether lymphadenopathy is due to reactive hyperplasia, infection, metastatic malignancy, or malignant lymphoma.[4]

The study was performed to assess the various cytomorphological patterns of the lymph node aspirates in patients presenting with peripheral lymphadenopathy.


  Subjects and Methods Top


This prospective study was conducted in the Department of Pathology in a government facility with limited resources from July 2019 to January 2020. The study included 81 patients of all age groups and both sexes who underwent FNA for palpable peripheral lymphadenopathy, either single or multiple, after obtaining informed consent. Ultrasound-guided FNA was done for deep-seated nodes and lesions measuring<1 cm.

A brief clinical history followed by physical examination was done and the findings were noted. FNA was performed under aseptic precautions using 22–24 gauge needle attached to 10 ml syringe. The aspirated material was smeared on to the glass slides. The smears were then fixed in 95% ethyl alcohol and stained with hematoxylin and eosin stain. Giemsa stain was done on air-dried smears. Ziehl–Neelsen (ZN) staining for acid–fast bacilli (AFB) was done whenever required. In cases where fluid was aspirated, the fluid was centrifuged and smears were made from the sediment, followed by the above mentioned staining methods. The cytological diagnosis for each case was made based on the cytomorphological patterns and available clinical information.

The diagnoses were categorized broadly into reactive lymphadenitis, tuberculous lymphadenitis, acute suppurative lymphadenitis, metastatic malignancy, and lymphoma. The cases of tuberculous lymphadenitis were further divided into three groups on the basis of cytomorphological patterns: Group 1 – epithelioid granulomas without necrosis, Group 2 – epithelioid granulomas with necrosis, and Group 3 – necrosis without epithelioid granulomas.


  Results Top


During the study period, a total of 81 patients presented with peripheral lymphadenopathy, of which 30 were males and 51 were females [Table 1]. The male:female ratio was 1:1.7. The age of the patients ranged from 3 to 83 years, with a mean age of 35.2 years. The maximum incidence of cases was seen in the age group of 11–20 years [Table 2].
Table 1: Sex distribution of patients with lymphadenopathy

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Table 2: Age distribution of patients with lymphadenopathy

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Cervical lymph nodes (72.83%) were more commonly involved followed by axillary lymph nodes (9.88%). Generalized lymphadenopathy and inguinal lymph nodes were rarely involved contributing to 1.23% each, respectively [Table 3].
Table 3: Site of lymphadenopathy

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Reactive lymphadenitis (48.15%) was the most common lesion followed by tuberculous lymphadenitis (33.33%). There were nine cases (11.11%) of acute suppurative lymphadenitis which was negative on AFB staining [Figure 1] and six cases (7.41%) of metastatic malignancy [Table 4]. The cases of metastatic malignancy in our study were mainly squamous cell carcinoma which involved the cervical and supraclavicular lymph nodes [Table 3] and [Figure 2].
Figure 1: Acute suppurative lymphadenitis – Smear showing scattered degenerated polymorphs in a necrotic background (Giemsa stain, ×100)

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Table 4: Diagnosis of aspirated lymph nodes

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Figure 2: Metastatic squamous cell carcinoma to lymph node – Highly cellular smear with sheets of malignant cells (H and E, ×100)

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Patients with tuberculous lymphadenitis most frequently presented with cervical lymphadenopathy [Table 3]. AFB positivity was noted in 13 out of 27 cases (48.15%) with tuberculous lymphadenitis. Based on the cytomorphological patterns, tuberculous lymphadenitis was further divided into three groups. Group 1 had three cases which were all AFB negative. Group 2 had 19 cases out of which eight were AFB positive. Group 3 had five cases which were all positive for AFB on ZN staining [Table 5] and [Figure 3].
Table 5: Cytomorphological patterns of tuberculous lymphadenopathy

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Figure 3: (a) Cytomorphological patterns of tuberculous lymphadenopathy. Group 1: Epithelioid granulomas without necrosis (Giemsa stain, ×100). (b) Epithelioid granulomas with necrosis (Giemsa stain, ×100). (c) Acid–fast bacilli positivity in Group 2 lesion (Ziehl–Neelsen stain for acid–fast bacilli, Oil immersion). (d) Group 3: Necrosis without epithelioid granulomas (Giemsa stain, ×100). (e) Acid–fast bacilli positivity in Group 3 lesion (Ziehl–Neelsen stain for acid–fast bacilli, Oil immersion)

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  Discussion Top


FNA is a simple, rapid, and minimally invasive diagnostic technique. It aids in early diagnosis and planning appropriate treatment for the patients. The knowledge of pattern of lymphadenopathy in a given geographical area is essential for making a confident and definite diagnosis or suspecting a disease.[5]

FNA of the lymph node is of great diagnostic value in lymphadenitis, lymphomas, and metastatic carcinoma. In developing countries like India, tuberculosis, acute upper respiratory tract infections, and suppurative lymphadenitis are some of the common causes of lymphadenopathy. It has been stated that any significant lymph node enlargement not subsiding or remaining static in size for more than 2 weeks after conventional antibiotics needs to be investigated thoroughly.[2],[6]

Female preponderance was noted in our study which was similar to a study by Badge et al.[7] Most of the patients belonged to the second and third decades of life which was also the case in the following studies.[7],[8]

Majority of the patients presented with cervical lymphadenopathy similar to the following studies.[8],[9],[10],[11] Reactive lymphadenitis was the most common lesion in our study which was in accordance with studies by Vimal et al., Biradar and Masur, and Ahmad et al.[2],[4],[12]

Tuberculous lymphadenitis was the second most common lesion in our study. The highest incidence of tuberculous lymphadenitis was seen in the second decade which was similar to the following studies.[4],[13],[14] Tuberculous lymphadenitis is the most common manifestation of extrapulmonary tuberculosis and occurs due to lymphatic spread from a primary focus. It commonly involves the cervical group of lymph nodes which is attributed to the rich lymphatic supply of the region, which was also a similar finding in our study.[13] The cytomorphological patterns in tuberculosis are varied and can be divided into three groups [Table 5].

In India, tuberculosis is most common compared to other granulomatous diseases; hence, the presence of granulomas is highly suggestive of tuberculous lymphadenitis and should be started on antituberculous treatment. In our study, of 27 cases, three cases showed epithelioid granulomas without necrosis and all were negative for AFB [Table 5]. Other possibilities of nonnecrotizing epithelioid granulomas were ruled out based on additional clinical history and examination findings. History of recent travel, any injury, pet exposure, abdominal pain, diarrhea, loss of appetite, malaise, joint pains, weight loss, drug history, and prior surgery were obtained. Examination of general build and nourishment of the patient, presence of any skin lesions, loss of sensation, and assessment for palpable splenomegaly were done in addition to routine clinical examination. Cervical lymph node was involved in two cases followed by supraclavicular lymphadenopathy in one patient. In Group 1 lesions, the AFB positivity is usually very low, and in cases negative for AFB, other possibilities such as sarcoidosis must be considered in the differential diagnosis. However, in underdeveloped and developing countries like India where tuberculosis is very common, based on patient history and clinical features, Group 1 lesions must be considered as tuberculous lymphadenitis unless proven otherwise.[15]

Nineteen out of 27 cases showed epithelioid granulomas with necrosis (Group 2), of which eight were AFB positive [Table 5]. Tuberculosis was confirmed in these cases by positive sputum microscopy. AFB positivity rate is usually high in the presence of necrotic material in the background, which is in accordance with the other studies.[16] This could be due to the immunocompromised state or inadequate cell-mediated response.

Of 27 cases, five showed necrosis without epithelioid granulomas (Group 3) and all were positive for AFB [Table 5]. Group 3 lesions with 100% AFB positivity were also noted in a study by Badge et al.;[7] AFB positivity was most commonly found in those smears in which there was only caseous necrosis present.[17],[18] These lesions are degenerated granulomas which show a positive reaction for the tuberculous antigen. Das et al. stated that foci of necrosis were associated with marked proliferation of tubercle bacilli and infiltration of polymorphs, whereas lymphocytes, epithelioid cells, and multinucleated giant cells are likely to have some role in limiting the proliferation of AFB.[3],[19] When proliferation of bacilli in a lymph node is unchecked, the lymph node becomes necrotic and turns into an abscess. Hence, FNA from a tubercular abscess contains more AFBs than early tuberculous lesions of the lymph nodes. The chances of finding AFB are greater when pus or caseous material is aspirated. The aspiration of caseous material is almost always indicative of tuberculosis and warrants an active search for AFB.[20] The typical necrotic background comprising eosinophilic granular material containing nuclear debris was described as “tubercular diathesis.” The cases which lack these characteristic finding and that which shows scattered epithelioid cells with or without granuloma or only necrotic material were diagnosed as tuberculous lymphadenitis when tubercular diathesis was seen in the smears even though AFB was absent on ZN staining.[21] Excision biopsy of the tuberculous lymph nodes is considered dangerous as it can lead to fistula formation and spread of the disease.

It has been stated that the number of AFB in the smear corresponds to the immune status of the patient. There must be 10,000–100,000 organisms/ml of the sample to detect AFB in an FNA smear.[22] AFB positivity in smears of tuberculous lymphadenitis varied between 40.6% and 56.4%. AFB positivity by ZN staining in our study was 48.15%. The detection of AFB was more frequent in the smears containing necrotic material alone than in those with granulomas. These findings had been observed in other studies too.[2]

Acute suppurative lymphadenitis was noted in nine patients of which seven of them presented with cervical lymphadenopathy [Table 3]. All these cases were negative on AFB staining. Acute suppurative lymphadenitis is often confused with caseous necrotic material with marked polymorphonuclear infiltration in tuberculosis. A careful search for the presence of epithelioid histiocytes should be made in such cases. The neutrophilic infiltrate could be due to the secondary immune response to the necrotic infiltrate.[2]

In our study, metastatic malignancy was mainly metastatic squamous cell carcinoma which involved the supraclavicular and cervical lymph nodes equally [Table 3]. Squamous cell carcinoma was the most common lesion to metastasize to lymph nodes, which was in concordance with the following studies.[2],[17],[23] No patient was diagnosed of lymphoma during the conduct of our study.


  Conclusions Top


FNA is an easy and inexpensive technique done to aid the early diagnosis of lymph node aspirates. It is an ideal tool that can be used as a basic investigation for lymphadenopathy in resource-limited settings. It is the safest alternative to excision biopsy of lymph nodes, especially in tuberculous lymphadenitis, which leads to fistula formation. Cervical lymph node enlargement was the frequent presentation of patients for FNA. Reactive lymphadenitis was the most common lesion in patients with palpable peripheral lymphadenopathy followed by tuberculous lymphadenitis. Epithelioid granulomas with or without necrosis and/or AFB positivity on cytological smears and with associated clinical symptoms should be considered as tuberculosis in our clinical setup unless proven otherwise. FNA also helps in diagnosing neoplastic and metastatic lesions and gives further clue regarding the origin of the primary tumor.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Acknowledgement

The authors would like to thank the Departments of Pathology, Radiology and General Surgery for their support and guidance.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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