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 Table of Contents  
LETTER TO THE EDITOR
Year : 2022  |  Volume : 14  |  Issue : 6  |  Page : 642-645

Synchronous oral squamous cell cand nodal tuberculosis: Need for consensus in treatment and management


Department of Oral Pathology and Microbiology, Saveetha Dental College and Hospitals, Chennai, Tamil Nadu, India

Date of Submission31-Jul-2022
Date of Acceptance28-Sep-2022
Date of Web Publication30-Dec-2022

Correspondence Address:
Dr. Deepak Pandiar
Department of Oral Pathology and Microbiology, Saveetha Dental College and Hospitals, Chennai, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jioh.jioh_169_22

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How to cite this article:
Ramasubramanian A, Ramani P, Pandiar D, P K R. Synchronous oral squamous cell cand nodal tuberculosis: Need for consensus in treatment and management. J Int Oral Health 2022;14:642-5

How to cite this URL:
Ramasubramanian A, Ramani P, Pandiar D, P K R. Synchronous oral squamous cell cand nodal tuberculosis: Need for consensus in treatment and management. J Int Oral Health [serial online] 2022 [cited 2023 Jan 31];14:642-5. Available from: https://www.jioh.org/text.asp?2022/14/6/642/366431



Oral squamous cell carcinoma (OSCC) is one of the most common malignancies with an annual incidence reaching over 300,000 cases and developing nations contribute to approximately 62% of the cases.[1] The most influential prognostic factor for OSCC is the regional node status as more than 40% of patients have node metastasis at the time of diagnosis. Also presence of nodal metastasis reduces the survival rate of patients to approximately 50%. Thus, treatment planning and management of neck nodal metastasis is a decisive factor for the prognosis of patients with OSCC. Further adding to the deluge that certain diseases like tuberculosis (TB) may be silently harbored by the patient and can have a profound effect when diagnosed in resected lymph nodes of these patients for the subsequent postsurgical treatment protocol and follow-up.

TB is still highly prevalent in Asian countries with nearly one-fourth of the global cases being reported in India.[2] With widespread awareness and anti-tubercular drugs, TB has been under control to a large extent but there is a resurgence of TB owing to drug resistance and immunosuppressive conditions, especially in patients with human immunodeficiency virus (HIV). It is estimated that one-quarter of humanity is infected with mycobacterium without symptomatic and microbiological evidence of disease which is clinically considered as latent TB.[3]

The prevalence of extra-pulmonary TB has been reported to be approximately 15%–20% of all the cases of TB in endemic countries and in this more than 50% of cases have been reported in immunocompromised patients.

Head and neck TB may be reflected as 0.60% as comorbidity with malignancy.[2] Tuberculous granulomas that arise in lymph nodes are in many aspects different from granulomas that form in the lungs. It has been demonstrated by scientists that lymph node granulomas form in the T- and B-cell regions of the lymph node characteristically lack B-cell-rich tertiary lymphoid features that are seen in the periphery of a lung granuloma. Also lymphocyte cuff regions found in lung granulomas are also less frequently encountered in lymph node granulomas. These findings retain the fact that varied differences between lymph node and lung granulomas could be attributed to the poor mycobacterium-killing potential of lymph nodes. It has also been observed that these tuberculous lymph nodes showed enormous remodeling and studded with dendritic cells and macrophages with relatively stable T-cell proportions but the number of B cells was markedly reduced when compared to nonspecific reactive lymph nodes.[4]

It has been thus observed that lymph nodes can play a major role in the reactivation of latent TB caused by immunosuppression. Lymph nodes could be the niche for reactivation of latent TB with chances of dissemination to the lungs and other organs.[5] Several authors have suggested that in an immuno-compromised state like malignancy or HIV, depletion of CD4 cells, or neutralization of tumor necrosis factor can begin in the lymph nodes and can be seen in positron emission tomography computed tomography by viewing the metabolic activity of lymph nodes.[6]

Tuberculous granulomas present as caseating granulomas with low oxygen resource that is characterized by dead macrophages and Langhans giant cells surrounded by fibroblasts with varying amounts of other inflammatory cells. The latent TB granulomas are fibrotic lesions and are predominantly made up of fibroblasts with minimal macrophages. When the patient goes into an immuno-compromised condition like malignancy there is a tendency for these granulomas to liquefy and the bacteria are released from degraded granuloma to reactivate the TB. Mycobacterium tuberculosis (Mtb) under-treated and controlled conditions in granuloma can get reactivated when availability of nutrients, re-oxygenation, and immune compromisation of the host which can lead to activation of different sets of genes that are required for the re-growth of the bacilli.[7] During reactivation, Mtb expresses Clp protease gene Regulator (ClpgR) and its inducible genes Clp proteases. Clp proteases maintain the protein levels, discard unwarranted proteins and help the bacteria to shift to the metabolic phase.[8] It also expresses five resuscitation-promoting factors and universal stress proteins that are essential for the lysis and reactivation of bacteria.

In addition to the well-known increased TB risk in patients with malignant disorders that is secondary to the immuno-suppressive effects of some of the therapies including steroids, chemotherapeutic drugs, or any other immune dysfunction especially in advancing age especially poorly controlled diabetes mellitus. We have observed incidental finding of tuberculous lymph nodes in only nine cases of OSCC over a period of 15 years signifying that it is a rare event [Table 1]. [Figure 1] shows histopathological features of gingiva-buccal OSCC with concomitant multiple tuberculous nodes in level III (Case 3).
Table 1: Clinicopathological profile of nine cases of oral squamous cell carcinoma with concomitant tubercular lymphadenitis

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Figure 1: Photomicrograph of H&E stained section from Case 3 showing (A) moderately differentiated squamous cell carcinoma and (B–D) multiple granulomas with Langhans type giant cells mixed with epitheloid cells in lymph nodes

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We can have two ways of looking into the scenario when we report tuberculous lymph nodes. One is that as the source of reactivation has been removed during the neck dissection, the possibility of dissemination gets reduced in these patients. However, we would be ignorant of the fact that the head and neck carcinoma has already initiated the reactivation sequence before the removal of the affected lymph nodes. There is evidence of the onset of active TB during head and neck carcinoma treatment when active pulmonary TB was not observed at the start of the treatment. So once we report tuberculous lymph nodes in excised nodes it mandates to go for Interferon gamma radio-assay (IGRA) as it is more accurate than tuberculin sensitivity test (TST) and has a better sensitivity in immuno-suppressed patients but cannot distinguish latent or active TB.[9] Polymerase chain reaction provides a sensitivity of 45%–75% and specificity of 97.3%–100% in samples of cervical tuberculous lymphadenopathies.[10]

There are no proper guidelines on the approach for the treatment of head and neck carcinoma with TB lymph nodes. But in a ground situation, once a patient has a histopathological report of tuberculous granuloma in lymph nodes, all necessary investigations as mentioned above would act as a useful tool to assess disease. Generally, then the treatment for TB is given priority. But the treatment plan gets jeopardized as to whether to suspend treatment of head and neck carcinoma, which may alter the prognosis for the patient as following surgery use of out-patient chemotherapy and maybe radiotherapy, becomes restricted. Also, several novel maintenance drug therapies due to regular steroid use and/or reduced immunity due to long-term maintenance chemotherapy are an ideal setting for the dissemination of TB.[11] The situation especially in patients who are harboring latent TB and when not in the immediate plan for neck dissection but proceeded by other treatment options is very critical as the patient is posed at another big threat of TB reactivation.[12]

There are limited guidelines for patients with head and neck carcinoma. Considering the reemergence of TB and especially in endemic countries like India where the burden of head and neck carcinoma is also very high, assessment of TB onset risks in patients with head and neck cancer should be mandated as a part of treatment planning for the patients reporting with head and neck carcinoma and optimal management methods. It has been reported by an Indian group that 42% of patients with head and neck cancer had evidence of TB at the time of diagnosis.[13] Therefore as part of the initial treatment planning protocol, it is recommended to perform IGRA test and sputum examination in all patients with head and neck carcinoma or at least in an immune modified state like in diabetes mellitus and mainly patients treated in out-patient radiotherapy and chemotherapy. Also since all patients undergo imaging of neck nodes disproportionate to the size of the primary tumor should raise the suspicion of a secondary cause, especially TB.[14] Some centers have given prophylactic isoniazid regimes for high-risk patients and those who have undergone screening before the commencement of head and neck cancer treatment.[11] It has been a struggle for the patients of those who have been diagnosed with tuberculous lymph nodes after neck dissection as it poses the treating physician a bigger challenge to counter two deadly diseases at the same time. It is time to develop a consensus protocol when treatment planning is initiated for head and neck cancers so that there is better evidence-based decision-making that ultimately the patient and society are benefited.

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Acknowledgement

Not applicable.

Financial support and sponsorship

There was no funding involved with this project.

Conflicts of interest

There are no conflicts of interest.

Authors contributions

AR: Conceptualization and collection of the data; PR: drafted the manuscript; DP: preparation of tables and figures, literature search, guarantor and editing of manuscript; RPK: editing and review.

Ethical policy and institutional review board statement

The manuscript includes the data from the archival medical records of the institute with no additional psychological, physical and financial burden for the patient.

Patient declaration of consent

Further, the informed and written consents were taken from the patients at the time of admission for treatment. The patients were aware that their identity shall not be revealed.

Data availability statement

Not applicable.



 
  References Top

1.
Anand R, Pandiar D, Kamboj M Financial burden of oral squamous cell carcinoma in India. Oral Oncol 2020;103:104528.  Back to cited text no. 1
    
2.
Libshitz HI, Pannu HK, Elting LS, Cooksley CD Tuberculosis in cancer patients: An update. J Thorac Imaging 1997;12:41-6.  Back to cited text no. 2
    
3.
Matsuo M Development of active tuberculosis during treatment of head and neck carcinoma: A case series. J Med Case Rep 2019;13:162.  Back to cited text no. 3
    
4.
Lin PL, Ford CB, Coleman MT, Myers AJ, Gawande R, Ioerger T, et al. Sterilization of granulomas is common in active and latent tuberculosis despite within-host variability in bacterial killing. Nat Med 2014;20:75-9.  Back to cited text no. 4
    
5.
Young DB, Gideon HP, Wilkinson RJ Eliminating latent tuberculosis. Trends Microbiol 2009;17:183-8.  Back to cited text no. 5
    
6.
Schöder H, Yeung HW, Gonen M, Kraus D, Larson SM Head and neck cancer: Clinical usefulness and accuracy of PET/CT image fusion. Radiology 2004;231:65-72.  Back to cited text no. 6
    
7.
Lin PL, Rodgers M, Smith L, Bigbee M, Myers A, Bigbee C, et al. Quantitative comparison of active and latent tuberculosis in the cynomolgus macaque model. Infect Immun 2009;77:4631-42.  Back to cited text no. 7
    
8.
Biketov S, Potapov V, Ganina E, Downing K, Kana BD, Kaprelyants A The role of resuscitation promoting factors in pathogenesis and reactivation of mycobacterium tuberculosis during intra-peritoneal infection in mice. BMC Infect Dis 2007;7:146.  Back to cited text no. 8
    
9.
Sarda AK, Bal S, Singh MK, Kapur MM Fine needle aspiration cytology as a preliminary diagnostic procedure for asymptomatic cervical lymphadenopathy. J Assoc Physicians India 1990;38:203-5.  Back to cited text no. 9
    
10.
Jha BC, Dass A, Nagarkar NM, Gupta R, Singhal S Cervical tuberculous lymphadenopathy: Changing clinical pattern and concepts in management. Postgrad Med J 2001;77:185-7.  Back to cited text no. 10
    
11.
Kamboj M, Sepkowitz KA The risk of tuberculosis in patients with cancer. Clin Infect Dis 2006;42:1592-5.  Back to cited text no. 11
    
12.
Kaplan MH, Armstrong D, Rosen P Tuberculosis complicating neoplastic disease. A review of 201 cases. Cancer 1974;33:850-8.  Back to cited text no. 12
    
13.
Kumar RR, Shafiulla M, Sridhar H Association of tuberculosis with malignancy at Kimio–an oncology centre. Indian J Pathol Microbiol 1999;42:339-43.  Back to cited text no. 13
    
14.
Chaturvedi P, Pai PS, Chaukar DA, Deshpande MS, Rangarajan V, Purandare N, et al. Extensive tubercular neck lymphadenopathy in a man with early-stage tongue cancer. Nat Clin Pract Oncol 2007;4:726-8.  Back to cited text no. 14
    


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