Superficial and Deep-seated Tuberculous Lesions: Fine-Needle Aspiration Cytology Diagnosis of 574 Cases Dilip K. Das, M.D., Ph.D., Suresh Bhambhani, M.D., Jiwa N. Pant, Dlp./M.L.T., Suraj Parkash, Msc., N.S. Murthy, M.Sc., Suresh T. Hedau, M.Sc., Pushpa Sodhani, M.D., and Chandra S. Pant, M.D., v.S.M.

Over a period of 2 yr (1987-1988), FNA smears in 574 cases were found to have cytologic features suggestive of or consistent with tuberculous lesions. The age of the patients ranged from 6 mo to 75 ye, with a median of 24 yr. The male to female ratio was 2731301. Sites of FNA were superjcial lymph nodes (SLN) in 440 (76.7percent) cases, superjcial extranodal sites (SENS) in 50 (8.7 percent), both SLN and SENS in 7 (1.2%), the thoracic cavity in 16 (2.8%), and the abdominal cavity in 61 (10.6%). Cytologic features were described under 3 major cytologic patterns, i.e., type I: epithelioid granuloma without necrosis, type IL epithelioid granuloma with necrosis, type III: necrosis without epithelioid granuloma. Type I, II, and III reactions were observed in 181 (31.5%), 183 (31.9%), and 210 (36.6%) cases, respectively. The overall AFB positivity was 30.8%. The AFB positivitiesfor type I, II, and III cytologic reactions were 5.4%, 32.0%, and 48.5%. respectively. The AFB positivity was low (< 30.0%) in swellings of the body surface (23.8%) and abdominal organs (18.9%). High positivity (> 60.0%) was observed in lesions of the thorax (63.6%) and thyroid (62.5%). Diagn Cytopathol 1992;8:211215.

1992 Wiley-Liss, Inc.

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Key Words: Epithelioid granuloma; Necrosis; FNAC; Lymph node; Extranodal; Thorax; Abdomen; Ultrasonogram

Over the past 2 decades, there have been a number of publications exclusively on fine-needle aspiration (FNA) diagnosis of tuberculous lesions in general and in speand breast. cific sites such as the lung, lymph node, Attempts have been made to classify the fine-needle aspirate based on macroscopic appearance and microscopic features, and to correlate it with the acid-fast-bacilli (AFB)-positive rate.



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Received May 10, 1991. Accepted October 8, 1991. From the Institute of Cytology and Preventive Oncology (ICMR), New Delhi and Institute of Nuclear Medicine and Allied Sciences, Delhi, India. Address reprint requests to Dr. Dilip K. Das, M.D., Ph.D., Asst. Professor, Dept of Pathology, Faculty of Medicine, Kuwait University, PO Box 24923, Safat 13110, Kuwait. Cc,

1992 WILEY-LISS, INC

Over a period of 2 yr, 574 cases with FNA cytologic features suggestive of or consistent with tuberculosis were seen at the Institute of Cytology and Preventive Oncology (ICMR). We intend to describe the frequency with which the various superficial and deep-seated organs were involved by tuberculous lesion, the cytomorphological features, and the acid-fast-bacilli-positive rates.

Materials and Methods The 574 cases included in this study constituted 15.3 percent of a total of 3,742 cases subjected to FNAC during this period. The age of the patients ranged from 6 mo to 75 yr, with a median of 24 yr. A total of 59.8% of the patients were in the second or third decade. The male to female ratio was 273:301. FNA was done with a 20-ml plastic disposable syringe and 22- to 23-gauge disposable needles fitted with Franzen’s syringe handle. For the lesions in the thoracic and abdominal cavities, ultrasound-guided FNA was performed. The sites of FNA were superficial lesions in 497 (86.6 percent), the thoracic cavity in 16 (2.8 percent), and the abdominal cavity in 61 cases (10.6 percent). The air-dried smears were stained with the May-Griinwald-Giemsa (MGG) stain for routine cytodiagnosis. In a few cases wet-fixed smears were also stained with Papanicolaou stain. One of the smears was stained with Ziehl-Neelsen (Z-N) stain for AFB in 5 19 cases. The diagnostic criteria for tuberculosis were based on already described cytomorphological and microbiological features, as depicted in Table I. The cellular reactions observed in tuberculous lesions of various sites and the rate of AFB positivity were determined. Whenever required, the values were compared using the test to determine the significance in the difference between the variables.

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DAS ET AL Table I. Smears

Diagnostic Criteria for Tuberculous Lesions in FNAC

Cytologic feature

Ziehl Neelsen stain

Diagnostic label

A. Epithelioid cells t multinucleated giant cells & necrosis

a) AFB positive b) AFB negative

B. Necrotic material without epithelioid cells

a) AFB positive b) AFB negative

a) Tuberculous lesion b) Granulomatous lesion likely to be of tuberculous etiology; however, stain for AFB is negative a) Tuberculous lesion b) Repeat FNAC advised for cytomorphological study, Ziehl-Neelsen staining, and/or for culture of AFB

AFB = acid-fast bacilli; FNAC = fine-needle aspiration cytology.

Results The frequency of distribution, cellular reaction, and AFB positivity of the cases with involvement of superficial sites are shown in Tables I1 and 111. Table IV shows these features for cases with intra-thoracic, and intra-abdominal lesions. In 497 (86.6%) cases the superficial sites were the target of FNA. These included lymph nodes, extranodal locations, and both these sites in 440, 50, and 7 cases, respectively. Of the total 447 patients with superficial lymphnode involvement, 406 had lymph nodes in the head and neck region. Axillary and inguinal lymphadenopathy were present in 30 and 7 cases, respectively. In only 4 cases were 2 lymph-node groups the site of FNA. The superficial extranodal organs were the breast (12 cases), thyroid (8 cases), testis and epididymis (6 cases), and salivary gland (3 cases). Lesions on the body surface in the form of cold abscesses and sinuses were noticed in 22 and 6 cases, respectively. Tuberculous lesions were located in the thorax and abdominal cavities in 16 and 61 cases, respec-

tively. Of the thoracic sites, 14 were from the lungs and 2 were mediastinal lymph nodes. The abdominal sites included the abdominal lymph nodes (25 cases), gastrointestinal tract (GIT) (15 cases), liver (8 cases), kidney (3 cases), gall bladder (2 cases), pancreas (1 case), and other abdominal sites (5 cases). Both GIT and abdominal lymph nodes were aspirated in 2 cases. The cytologic features of tuberculous lesions were grouped under 3 major cytologic response types as follows: Type I: Epithelioid granuloma without necrosis (Fig. 1) Type 11: Epithelioid granuloma with necrosis Type 111: Necrosis without epithelioid granuloma that was either completely acellular (Fig. 2) or accompanied by polymorphonuclear infiltration (Fig. 3 A ) .

The site of FNA could sometimes be made out from the accompanying cells of the affected organs, i.e., bronchial cells and pulmonary macrophages in lesions of lung, hepatocytes in tuberculosis of liver, and ductular cells from breast lesions. The type I, 11, and I11 reactions were observed in 181 (31.5%), 183 (31.9%), and 210 (36.6%), respectively. Amongst the lymph-node aspirates, the type I, 11, and I11 reaction patterns were seen in decreasing order of frequency, i.e., 157, 149, and 141, respectively, whereas in case of superficial extranodal sites, there was an increasing order of frequency for these 3 reaction types, i.e., 9, 12, and 36, respectively. The type 111 reaction was very common in lesions of the breast and was overwhelmingly seen in aspirates from cold abscesses on the body surface. The aspirates from deep-seated lesions also showed the type I, 11, and I11 reaction in increasing order of frequency, i.e., 18,23, and 36, respectively. The type I11 reaction was very common feature in lung and liver aspirates. An inflammatory picture due to the presence of significant numbers of neutrophils in varying stages of degeneration was a prominent feature in aspirates from the breast (8 of 12 cases), thyroid (5 of 8 cases), swellings and sinuses on body surface (17 of 28 cases), and intestine (8 of 17 cases).

Table 11. FNA Cytodiagnosis of Tuberculous Lesions of Superficial Sites: Frequency of Distribution, Cytologic Patterns, and AFB Positivity AFB positivity Cellular reaction No. of No. f VE/ Site of' FNA case1 I II III no. tested (%I A. Superficial lymph nodes (SLN) B. Superficial extranodal sites (SENS) C. SLN SENS

+

440 50 7

154 9 ( -

149 10 1

137 31 6)"

12.51'401 11/45 5/7b

(31.2) (24.4) (71.4)

Total 497 163 160 174 141/45 3 (31.1) Cellular reaction type I: epithelioid granuloma without necrosis; 11: epithelioid granuloma with necrosis; 111: necrosis without epithelioid granuloma. "Overall cellular reactions. Individually lymph nodes showed type 1, 11, and 111 reactions in 3, 0, and 4 cases, respectively. Extranodal sites showed these reactions in 0, 2, and 5 cases, respectively. 'Overall AFB positivity. In lymph-node aspirates AFB was detected in 3/7 cases and in extranodal sites in 5/7 cases.

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FNAC DIAGNOSIS OF TUBERCULOSIS Table 111. Tuberculous Lesions of Superficial Extranodal Sites: Frequency of Distribution, Cytologic Patterns, and AFB Positivity AFB positivity

Site of FNA

Cellular reaction

No of cases

I

II

111

No. + VE/ no. tested

1 5 1

4/11 5/8 0/2 0/5 5/2 1 2/ 5

(36.4) (62.5)

16/52

(30.7)

Breast Thyroid Salivary gland Testis and epididymis Swellings on body surface Sinuses on body surface

12

3

8 3 6 22 6

-

2 3

-

8 3 1 4 17 3

Total

57

9

12

36

1 -

2 3

(%)

(0.0) (0.0)

(23.8) (40.0)

Cellular reaction type I: epithelioid granuloma without necrosis; 11: epithelioid granuloma with necrosis; 111: necrosis without epithelioid granuloma.

Table IV. Positivity

Tuberculous Lesions of Deep-seated Sites (Thorax and Abdomen): Frequency of Distribution, Cytologic Patterns, and AFB AFB positivity

No. of cases

Site of FNA

Cellular reaction

I

II

111

No. 4- VE/ no. tesred

(%)

(100.0)

A. Thoracic cavity Lungs Mediastinal LN B. Abdominal cavity Abdominal LN Abd. LN + GIT GIT Gall bladder Liver Kidney Other abdominal sites

14 2

1 1

7/11 2/2

25 2 15 3 8 3 5

7

6/22 1/2 1/14 0/2 0/7 0/2 2/4

(27.3) (50.0) (7.1)

Total

77

19/66

(28.8)

1

6 1 1

-

18

23

36

(63.6)

(0.0) (0.0) (0.0)

(50.0)

Type I: epithelioid granuloma without necrosis; 11: epithelioid granuloma with necrosis; 111: necrosis without epithelioid granuloma. GIT = gastrointestinal tract; Abd = abdomen; L N - = lymphnode.

Of the 519 cases, AFB was demonstrated in ZiehlNeelsen-stained smears in 160 (30.8%) cases. The numbers of cases with the type I, 11, and I11 reaction screened for AFB were 147, 172, and 200, respectively. AFB was detected in 8 (5.4%), 55 (32.0%), and 97 (48.5%), respectively, the difference between the above 3 groups being highly significant = 73.82, P < 0.001). The AFB positivity was 3 1.1% for superficial lesions and 28.8% for deep-seated lesions. Amongst the superficial lesions, the AFB positive rate was 31.2% for the lymph node and 24.4% for extranodal sites. There was a small group of 7 cases in which both lymph-node and extranodal sites were punctured. The rate of AFB positivity was 7 1.4% in this group. Amongst deep-seated lesions, AFB positivity was 69.2% for intrathoracic and 18.9% for intra-abdominal lesions. Not only were very few cases with type I reaction positive for AFB, but also very rare bacilli were observed in the positive Z-N-stained smears with the type I cellular reaction. In cases with the type I1 and I11 reactions, the concentration of bacilli showed a wide variation, starting

(x2

from rare bacillus to an overwhelming population of AFB (Fig. 3B).

Discussion Tuberculosis continues to be a major problem of public health interest in India. The prevalence of infection is of the order of about 40% in all age groups, and the mortality is 80-100/100,000, the highest tuberculosis death rate anywhere in the world. We have seen 574 cases in 2 yr, which is 15% of all cases sent for FNA during this period. From this, the magnitude of the problem in a hospital setup can also be appreciated. According to Baily,8 the incidence of infection is highest in individuals between the ages of 5 and 20 yr, and the prevalence is highest (about 70%) at the age of 35 yr. The above figures refer to pulmonary tuberculosis. Although most of our cases (97.6%) were a nonrespiratory type of tuberculosis, the age distribution also showed that the majority of the patients were young, i.e., nearly 60% were in the second and third decades.

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DAS ET AL.

Pig. 1. (A) FNA smear from a bowel mass in a 12-yr-old boy. The smear shows a group of epithelioid cells mixed with a few lymphocytes (MGG X 160). (B) FNA smear from the right supraclavicular lymph node in a 46-yr-old man. Typical Langhan’s giant cell seen along with epithelioid cells (MGG x400).

Unlike pulmonary tuberculosis, in which exfoliative cytology has been used extensively for cytodiagnosis, the nonrespiratory type of tuberculosis has been diagnosed mostly by FNA, as evident from recent reports. Exclusive studies on the utilization of FNA for the diagnosis of pulmonary tuberculosis are very few. 3,18 This may be due to the easy availability of exfoliated specimens from the respiratory tract for cytological and bacteriological studies, on the one hand, and the complications associated with FNAC of lung, on the other. We have resorted to FNA of lung only in those cases of pulmonary tuberculosis in which sputum was negative for AFB or when malignancy was a strong clinical possibility. Therefore, the frequency of pulmonary tuberculosis was only 2.4% of the 574 cases. 294-7,15-17

Fig. 2. FNA smear from right lung of an 1 I-mo-old baby. The smear shows acellular necrotic material. However, the stain for AFB was positive (MGG X 160).

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Diugnortic Cytoputhology, Vol 8, No 3

Fig. 3. (A) FN A smear from anterior mediastinal mass of a 50-yr-old female. The smear shows polymorphs, a film of liquified necrotic material in the background, and unstained areas representing AFB (MGG X640). (B) Ziehl-Neelsen stained smear of the case shown in Fig. 3A. Numerous acid-fast bacilli resembling the smears made from a culture are seen (Ziehl-Neelsen stain x 640).

The lymph nodes were the most common site of FNA amongst our cases, accounting for about 78% of all sites. Similar observations have also been made in earlier studies in which 81%-82% were in the lymph nodes. But unlike other studies, the present communication describes the tuberculous lesions of a large number of nonrespiratory extranodal sites. Amongst the superficial extranodal sites, swellings and sinuses on the body surface (28 cases), breast (12 cases), thyroid (8 cases), and testidepididymis (6 cases) were the common sites. In earlier studies, Nayar and Saxena’ have described the FNA diagnosis of 12 cases of tuberculous mastitis, and Ranjwanshi et al. encountered 7 cases of sinuses amongst their cases. For a long time, the thyroid has been considered to be an extremely rare site involved by tuberculosis. l9v2O So far, tuberculous thyroiditis constitutes an isolated case in large series of tuberculous lesions diagnosed by FNA. I s 2 To our knowledge, FNA diagnosis of such a large number of tuberculous lesions presenting as swellings on the body surface or as goiters (as observed in this study) has not been described earlier. Amongst the deep-seated lesions, abdominal lymph nodes (27 cases) were the most common site, followed by the GIT (17 cases), lungs (14 cases), and liver (8 cases). The rarer sites were the kidney, gall bladder, and pancreas. There was strong clinical suspicion of malignancy in some of these cases. The useful role of FNA in arriving at a quick diagnosis without resorting to thickneedle biopsy, laparoscopy, or exploratory laparotomy need not be over-emphasized. Diagnosis of tuberculous lesions depends upon the demonstration of epithelioid granuloma with or without necrosis. Other reactive components, such as lymphocytes, polymorphs, and Langhan’s giant cells, may or may not be present. This is true for both the histology and cytol-

FNAC DIAGNOSIS OF TUBERCULOSIS

ogy. Those cases in which FNA smears contain necrotic material without epithelioid granuloma have also been considered as tuberculous lesions since, interestingly, the rate of AFB positivity is the highest i,2,6in such cases. FNA smears have been proved to be very useful for the demonstration of AFB. i,2,4,6The overall AFB positivity observed in this study (30.8%) was lower than in earlier studies from this laboratory, 2*6wherein it was in the range of 45%-55%. The lower rate was largely due to an observation error, since thorough rescreening of 57 ZiehlNeelsen-stained smears, which were initially reported as negative, revealed AFB in 7 more cases. AFB positivity was low ( < 30%) in superficial lesions such as swellings on the body surface (23.8%), and in deep-seated lesions, such as those of the intra-abdominal organs as a whole (18.8%). On the other hand, high positivity (> 60%) was observed in the thyroid (62.5%) and in intrathoracic lesions (69.2%). It is known that AFB positivity is highest in caseous lesions, and the present study reconfirms this finding. In thyroid and thoracic lesions, there was evidence of caseation in 100% and 87.5% of cases, respectively, which is very high. However, the frequency of caseation was also reasonably high in swellings of the body surface (77.3%) and intra-abdominal lesions (73.8%). Therefore, development of caseation in a tuberculous lesion may not be the only factor responsible for the proliferation of tubercle bacilli. It is known that the tubercle bacilli do not proliferate in the center of closed caseous areas, yet they often multiply at an enormous rate if aeration is reestablished, as by a bronchus or blood vessel opening into the lesion. 2i But, how far aeration was reestablished in the caseous focii of our pulmonary tuberculosis cases and how much the high vascularity of thyroid contributed to the increased oxygen tension, and thereby to high AFB positivity, will remain a matter of conjecture. In the previous studies from our laboratory, the highest positive rate ( 280%) was encountered when necrosis was associated with neutrophilic infiltration. This could not be reconfirmed in the present study, wherein the highest AFB positivity (57.9%) was recorded in acellular necrotic material. Thus, the present study describes for the first time a large number of cases with tuberculous lesions of superficial as well as deep-seated organs diagnosed by fine-needle aspiration cytology, the cellular reaction observed in them, and the rate of AFB positivity. 29496

Acknowledgment The authors wish to thank Mrs. Alice Mathew and Mr. Sanjeev Kumar for their secretarial help in the preparation of this manuscript.

References 1 Bailey TM, Akhtar M, Ali MA. Fine needle aspiration biopsy in the diagnosis of tuberculosis. Acta Cytol 1985;29:732-6. 2. Rajwanshi A, Bhambhani S , Das DK. Fine needle aspiration cytology diagnosis of tuberculosis. Diagn Cytopathol 1987;3:13-6. 3. Dahlgren SE, Ekstrom P. Aspiration cytology in the diagnosis of pulmonary tuberculosis. Scand J Resp Dis 1972;53:196-201. 4. Metre MS, Jayaram G. Acid-fast bacilli in aspiration smears from tuberculous lymph nodes. An analysis of 255 cases. Acta Cytol 1987;31:17-9. 5 . Dandapat MC, Panda BK, Patra AK, Acharya N. Diagnosis of tubercular lymphadenitis by fine needle aspiration cytology. Ind J Tuberc 1987;34:13942. 6. Das DK, Pant JN, Chachra KL, Murthy NS, Satyanarayan L, Thankamma TC, Kakkar PK. Tuberculous lymphadenitis: Correlation of cellular components and necrosis in lymph node aspirate with A.F.B. positivity and bacillary count. Ind J Pathol Microbiol 1990; 31:l-10. 7. Nayar M, Saxena HMK. Tuberculosis of the breast: A cytomorphologic study of needle aspirates and nipple discharges. Acta Cytol 1984;28:325-8. 8. Bailey GVJ. Tuberculosis control in India: Current problems and possible solutions. Ind J Tuberc 1983;30:45-56. 9. Sivaraman S . Tuberculosis in India: The prospect. Ind J Tuberc I982;29:7 1-86. 10. Palva T, Saloheimo M. Observation on the cytologic pattern of bronchial aspirates in pulmonary tuberculosis. Acta Tuberc Scand 1955;31:278-88. 11. Nasiell M, Roger V, Nasiell K, Enstand I, Voge B, Bisther A. Cytologic findings indicating pulmonary tuberculosis. I. The diagnostic significance of epithelioid cells and Langhan’s giant cells found in sputum or bronchial secretions. Acta Cytol 1972;16:14651. 12. Roser V, Nasiell M, Nasiell K, Hjerpe A, Enstad I, Bisther A. Cytologic findings indicating pulmonary tuberculosis. 11. The occurrence in sputum of epithelioid cells and multinucleated giant cells in pulmonary tuberculosis, chronic nontuberculous lung disease and bronchogenic carcinoma. Acta Cytol 1972;16:538-41. 13. Verma K, Sandhyamani S , Pande JN. Cytologic diagnosis of pulmonary tuberculosis by bronchoalveolar lavage. Acta Cytol 1983;27: 21 1-2. 14. Tani EM, Schmitt FCL, Oliveira MLS, Gobetti SMP, Decarlis RMST. Pulmonary cytology in tuberculosis. Acta Cytol 1987;31: 460-3. 15. Patra AK, Nanda BK, Mohapatra BK, Panda AK. Diagnosis of lymphadenopathy by fine needle aspiration cytology. Ind J Pathol Microbiol 1983;26:273-8. 16. Tripathy SN, Mishra N, Patel NM, Samantray DK, Das BK, Mania RN. Place of aspiration biopsy in the diagnosis of lymphadenopathy. Ind J Tuberc 1985;32:13011. 17. Narang RK, Pradhan S, Singh RP, Chaturvedi S. Place of fine needle aspiration cytology in the diagnosis of lymphadenopathy. Ind Tuberc 1990;37:29-3 I. 18. Silverman JF, Marrow HG. Fine needle aspiration cytology of granulomatous diseases of the lung, including nontuberculous mycobacterium infection. Acta Cytol 1985;29:535-41. 19. Rankin FW, Graham AS. Tuberculosis of the thyroid gland. Ann Surg 1932;96:62548. 20. Levitt T. The status of lymphadenoid goitre. Hashimoto’s and Riedel’s diseases. Ann R Coll Surg 1952;10:369-404. 21 Milard M. Lung, pleura and mediastinum. In: Anderson, WAD ed. Pathology. 6th ed. St. Louis: C.V. Mosby, 1971:946.

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Superficial and deep-seated tuberculous lesions: fine-needle aspiration cytology diagnosis of 574 cases.

Over a period of 2 yr (1987-1988), FNA smears in 574 cases were found to have cytologic features suggestive of or consistent with tuberculous lesions...
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