Indian Journal of Pathology and Microbiology

: 2016  |  Volume : 59  |  Issue : 3  |  Page : 271--272

Combination of laboratory diagnostic tests for cutaneous tuberculosis

Ling-Juan Zhang 
 Department of Dermatology, School of Medicine, University of California, San Diego, California 92121, USA

Correspondence Address:
Dr. Ling-Juan Zhang
Department of Dermatology, School of Medicine, University of California, San Diego, California 92121

How to cite this article:
Zhang LJ. Combination of laboratory diagnostic tests for cutaneous tuberculosis.Indian J Pathol Microbiol 2016;59:271-272

How to cite this URL:
Zhang LJ. Combination of laboratory diagnostic tests for cutaneous tuberculosis. Indian J Pathol Microbiol [serial online] 2016 [cited 2022 Oct 5 ];59:271-272
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Tuberculosis (TB), a disease caused by Mycobacterium tuberculosis infection, is affecting approximately one-third of the world's population, with ~9 million new cases being reported every year.[1] While lung is the primary target of TB, it can also manifest to other organs as an extrapulmonary disease in ~10% of all TB cases. Cutaneous TB (CTB), TB of the skin, is the least common form of extrapulmonary TB (EPTB), comprising only ~2% of all EPTB manifestations.[2]

Diagnosis of CTB is challenging because most diagnostic methods have lower specificity and sensitivity rates for cutaneous presentation, compared to the pulmonary and other extrapulmonary forms.[3] In addition, in CTB, atypical clinical presentation often stimulates other inflammatory and neoplastic conditions, which are not uncommon, so histopathology may not be elucidative and conclusive. Therefore, multiple techniques need to be performed so that the sum of positive elements can create the basis for CTB diagnosis.

In a new study published in IJPM, the authors aimed to evaluate diagnostic laboratory tests available for CTB by performing various diagnostic laboratory tests. Tests that they performed include histopathological diagnosis, acid-fast Bacilli (AFB) staining, growth of mycobacteria in culture, and polymerase chain reaction (PCR) for mycobacteria-specific gene region. They have collected 26 skin biopsy specimens which were clinically suspected cases of CTB and 11 of those were diagnosed as CTB after microbiological evaluations or the ones negative for microbes but confirmed as CTB by histopathological evaluation. Within these 11 confirmed CTB specimens, ten samples (90.90%) were confirmed as CTB by histopathological confirmation and five samples (41%) showed positive growth of M. tuberculosis complex (MTBC) in culture media. Of the 11 samples, six samples were analyzed by PCR method to detect MTBC and two samples (33.33%) gave positive results. However, all the 11 patients diagnosed as CTB by bacteriological and/or histopathological evaluation gave negative results for the AFB staining test.

Results from this study suggest that although culture is still the “gold standard” for TB diagnosis,[4] other methods including histopathological evaluation and PCR method need to be combined with culture method for the diagnosis of CTB. They have shown that only 41% of confirmed CTB specimens gave positive growth of the mycobacteria, and all of those samples with negative MTBC growth in culture were confirmed as CTB by histopathological evaluation. Only one of out of 11 samples were not confirmed as CTB by histopathological evaluation, but this sample showed positive growth in culture and was thus diagnosed as CTB. The two skin specimens that gave a positive signal in the PCR were also positive for growth in culture and were confirmed as CTB by histopathological evaluation, validating the diagnosis of these two samples as CTB. However, the major drawback for the conventional method to culture mycobacteria is that the culture takes 4–6 weeks due to the slow growth rate of the organism. Newer rapid-culture technique involving radiometric culture media not only can shorten the culture time to 3–7 days but also can increase the sensitivity from 25% to 75% for CTB.[5]

The failure of microscopic observation of AFB in all smears suggests that although AFB staining method is simple and quick and requires minimal skills and equipment, its major drawback is its low and variable sensitivity and it cannot distinguish M. tuberculosis and nontuberculous bacteria. In consistent with their results, studies published by other groups show that <10% of all CTB cases were positive for AFB, and in another study, no AFB could be confirmed on routine examination of 100 CTB cases.[6],[7] Compared to AFB staining, PCR method is more sensitive and reliable and it can be used in the routine diagnostic algorithm when conventional methods fail to identify MTBC. It has been demonstrated that AFB detection limit is >104Bacilli per slide whereas the PCR methods gave satisfactory results as few as 100 bacteria per sample in a few hours.[8] In this study, ~33% of confirmed CTB specimens yielded positive signal by PCR method and other groups show that the overall sensitivity of PCR for smear negative specimens ranged from 25% to 72% in different studies. Variation of the sensitivity of PCR method may be explained by loss of DNA during extraction, presence of PCR inhibitors, and different fixatives used and variable fixation time because fixatives have been reported to diminish the PCR signal. This study used conventional PCR, but real-time PCR will be needed to quantify the number of MTBC per sample.

In summary, this study suggests that histopathology testing and isolation of M. tuberculosis in culture of skin specimens or by PCR are the best diagnostic tool for the detection and diagnosis of CTB. Their results from histopathology and bacteriology correlate and are complementary to each other, indicating that performing these two tests will increase the establishment of the diagnosis of CTB.


1Manych M. Tuberculosis – Information report DZK 2015. Pneumologie 2015;69:449.
2van Zyl L, du Plessis J, Viljoen J. Cutaneous tuberculosis overview and current treatment regimens. Tuberculosis (Edinb) 2015;95:629-38.
3Santos JB, Figueiredo AR, Ferraz CE, Oliveira MH, Silva PG, Medeiros VL. Cutaneous tuberculosis: Diagnosis, histopathology and treatment – Part II. An Bras Dermatol 2014;89:545-55.
4Eichbaum Q, Rubin EJ. Tuberculosis. Advances in laboratory diagnosis and drug susceptibility testing. Am J Clin Pathol 2002;118 Suppl:S3-17.
5Aggarwal P, Singal A, Bhattacharya SN, Mishra K. Comparison of the radiometric BACTEC 460 TB culture system and Löwenstein-Jensen medium for the isolation of mycobacteria in cutaneous tuberculosis and their drug susceptibility pattern. Int J Dermatol 2008;47:681-7.
6Gopinathan R, Pandit D, Joshi J, Jerajani H, Mathur M. Clinical and morphological variants of cutaneous tuberculosis and its relation to Mycobacterium species. Indian J Med Microbiol 2001;19:193-6.
7Ramesh V, Misra RS, Jain RK. Secondary tuberculosis of the skin. Clinical features and problems in laboratory diagnosis. Int J Dermatol 1987;26:578-81.
8Ruiz-Manzano J, Blanquer R, Calpe JL, Caminero JA, Caylà J, Domínguez JA, et al. Diagnosis and treatment of tuberculosis. Arch Bronconeumol 2008;44:551-66.