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  Table of Contents  
Year : 2021  |  Volume : 58  |  Issue : 3  |  Page : 473-475

Not just the tip of the iceberg: Commentary on Numb Chin syndrome

1 Department of Internal Medicine, Division of Adult Clinical Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
2 Division of Hematology and Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, United States of America

Date of Submission05-Jul-2020
Date of Decision07-Jul-2020
Date of Acceptance14-Dec-2020
Date of Web Publication02-Jul-2021

Correspondence Address:
Kamal Kant Sahu
Division of Hematology and Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah
United States of America
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijc.IJC_737_20

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How to cite this article:
Jandial A, Sahu KK. Not just the tip of the iceberg: Commentary on Numb Chin syndrome. Indian J Cancer 2021;58:473-5

How to cite this URL:
Jandial A, Sahu KK. Not just the tip of the iceberg: Commentary on Numb Chin syndrome. Indian J Cancer [serial online] 2021 [cited 2021 Oct 28];58:473-5. Available from: https://www.indianjcancer.com/text.asp?2021/58/3/473/320443

Two interesting cases of numb chin syndrome (NCS) in the setting of diffuse large B-cell lymphoma (DLBCL) have been published in this issue of IJC.[1],[2] NCS is a pure sensory neuropathy involving the mental nerve that manifests as numbness and tingling of the chin, lower lip, adjacent gingiva and buccal mucosa.[3] Considering limited published literature and clinical diversity, pursuing a one-size-fits-all investigative strategy for NCS is impracticable. These two cases highlight the perennial relevance of paying close attention to subtle yet vital clinical clues like NCS in routine practice. Likewise, they lay emphasis on embracing personalized approach to investigate such patients.

NCS was first described by Charles Bell in a case of metastatic breast cancer.[4] As per literature, dental procedures (e.g., molar extraction) are the commonest cause of NCS.[5] In patients with oro-dental causes, the involvement of inferior alveolar nerve trunk by the local extension of the inflammatory process compromises its function.[6] A systematic review on malignant NCS cases published until 2007 suggested that NCS as the initial presentation of malignancy vis-a-vis first sign of relapse was seen in nearly 27.7% and 37.7% cases, respectively. Breast cancer, hematological neoplasms (lymphomas and acute leukemias), and prostatic cancer were identified as the commonest causes of malignant NCS.[7]

The development of NCS in any patient can have major connotations. Firstly, it mandates exclusion of local oro-dental pathologies (dental infection, trauma, etc.,), before embarking on the quest for any systemic disorder.[5] Secondly, one should consider both benign and malignant disorders as differential diagnoses for NCS.[3],[7] In the absence of a dental cause, the likelihood of solid and hemato-lymphoid malignancies increases.[8] Determination of the nature of the underlying disease is indispensable for treatment and prognostication. Thirdly, among the cancer patients, NCS can be the first manifestation of the disease or a harbinger of recurrence.[7] Exploring previous clinical details can provide valuable leads in this regard. Fourthly, it can present as a solitary finding or as a part of disseminated disease with other signs and symptoms. Evaluation with appropriate imaging techniques for disease foci elsewhere in the body is necessary. The accessible sites can be targeted for histological diagnosis. Lastly, NCS is often considered an ominous sign in patients with recurrence of malignancy. Herein, it suggests advanced underlying disease and poor prognosis despite treatment. These patients are usually candidates for palliative care with mean survival of less than 1 year.[9]

Understanding of the local anatomy is essential to appreciate the potential sites where various pathologies can engage the inferior alveolar nerve along its course. A protracted and tortuous course of the nerve through the mandible, presence of vascular hematopoietic marrow and sluggish blood flow in the vicinity are the factors that render inferior alveolar nerve and its branches vulnerable.[10] Although the NCS diagnosis is conventionally clinical, radiological investigations are generally required for exact anatomical localization of disease focus. Theoretically, a lesion anywhere along the course of the trigeminal nerve can give rise to NCS – mandible (most common), base of skull, leptomeningeal space and, rarely axial central nervous system lesions. Other cranial nerve palsies and areflexia shall indicate skull base and leptomeningeal localization, respectively. Cerebrospinal fluid (CSF) examination is crucial to identify leptomeningeal deposits from metastatic tumors.[5]

The advancement in the field of radiodiagnosis and imaging has revolutionized the strategies to evaluate patients with occult malignancies. Previously, many patients with NCS used to remain undiagnosed despite dedicated work up.[3] But now a paradigm shift has taken place in the utilization of imaging techniques. The simple modalities like panoramic dental radiographs and bone scintigraphy can identify mandibular bony lesions with only limited detail on neural involvement. Contemporarily, the cross-sectional imaging with computed tomography (CT) of face and base of skull is the usual first choice in these settings. Magnetic resonance imaging (MRI) with gadolinium-enhancement can unveil perineural involvement, adjacent soft tissue lesions and leptomeningeal spread. However, mandibular details are generally not captured when MRI is performed as per routine protocol.[11] The functional imaging techniques like FDG-PET scan can identify hypermetabolic disease foci at baseline as well as on follow-up; however, due to poor spatial localization, it needs to be supplemented with other cross-sectional techniques like CT or MRI for clear lesion localization. The authors in case 1 have discussed the utility of magnetic resonance (MR) neurography using gadolinium-enhanced 3D SPACE STIR sequence technique, a novel approach to visualize small peripheral nerves. Given its high spatial resolution and soft tissue contrast, MR neurography has been in use since 1992 for the delineation of peripheral nerves which have complex anatomical courses. It has shown utility in depicting the roots and small branches of the brachial plexus and lumbosacral plexus.[12] The complex route that inferior alveolar nerve traverses through mandible makes MR neurography a suitable tool for its visualization. Nevertheless, it is important to understand that achievement of clinico-radiological correlation may not be possible in all such cases. In the context of NCS, apart from direct infiltration and mechanical compression, neural damage caused by microscopic deposition of malignant cells and immune-mediated injury may still remain covert despite high-resolution imaging.[13] Overall, it is likely that refinement in imaging techniques will assist the clinicians in better responding to diagnostic challenges posed by cancer patients with elusive clinical features like NCS and other similar syndromes.[14] Attempts to achieve clinico-radiological correlation in such scenarios will bolster the practice of evidence-based medicine and useful in follow-up of such patients.

To sum up, NCS represents a rare complication that can arise from local (dental) or systemic disorders, requiring prompt and detailed evaluation. In the absence of dental infection or trauma, the clinical value of NCS as an indicator of underlying malignancy is crucial. Like the metaphor 'tip of the iceberg', NCS can be a subtle presentation of sinister underlying disease. Like overlooking an iceberg, the underestimation of a dangerous entity like NCS can be catastrophic. It is the responsibility of the treating clinicians that they keep a high-index of suspicion and take utmost care while investigating such patients. A pragmatic approach, incorporating recent imaging techniques, customized to the patient profile can avoid unnecessary delays in the diagnosis and treatment.

  References Top

Jain A, Sankhe S. Numb chin syndrome secondary to infiltration of inferior alveolar nerve as a presentation of relapse in treated testicular lymphoma—diagnosis on PET/CT and MR neurography. Indian J Cancer [this issue - case report].  Back to cited text no. 1
Kudva A, Vineetha R, Gunashekhar S, Kudva R, Kumar M. Mental nerve paresthesia in non-Hodgkin lymphoma: A subtle sign of occult malignancy. Indian J Cancer [this issue - letter to the Editor].  Back to cited text no. 2
Lossos A, Siegal T. Numb chin syndrome in cancer patients: Etiology, response to treatment, and prognostic significance. Neurology 1992;42:1181-4.  Back to cited text no. 3
Jain A, Rajpal S, Sachdeva MUS, Malhotra P. Numb chin syndrome as a presenting symptom of diffuse large B-cell lymphoma with secondary myelofibrosis. BMJ Case Rep 2018:bcr2017221245. doi: 10.1136/bcr-2017-221245.  Back to cited text no. 4
Smith RM, Hassan A, Robertson CE. Numb Chin Syndrome. Curr Pain Headache Rep 2015; 19:44.  Back to cited text no. 5
Kalladka M, Proter N, Benoliel R, Czerninski R, Eliav E. Mental nerve neuropathy: Patient characteristics and neurosensory changes. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;106:364-70.  Back to cited text no. 6
Galan Gil S, Penarrocha Diago M, Penarrocha Diago M. Malignant mental nerve neuropathy: Systematic review. Med Oral Patol Oral Cir Bucal 2008;13: E616-21.  Back to cited text no. 7
Colella G, Giudice A, Siniscalchi G, Falcone U, Guastafierro S. Chin numbness: A symptom that should not be underestimated: A review of 12 cases. Am J Med Sci 2009;337:407-10.  Back to cited text no. 8
Lata J, Kumar P. Numb chin syndrome: A case report and review of the literature. Indian J Dent Res 2010;21:135-7.  Back to cited text no. 9
[PUBMED]  [Full text]  
Nambiar KR, Anoop TM, Haridas L, Daniel S. Numb Chin Syndrome as the initial manifestation of breast carcinoma. Indian J Surg Oncol 2018;9:391-3.  Back to cited text no. 10
Kim TW, Park JW, Kim JS. A pitfall of brain MRI in evaluation of numb chin syndrome: Mandibular MRI should be included to localize lesions. J Neurol Sci 2014;345:265-6.  Back to cited text no. 11
Zhang Y, Kong X, Zhao Q, Liu X, Gu Y, Xu L. Enhanced MR neurography of the lumbosacral plexus with robust vascular suppression and improved delineation of its small branches. Eur J Radiol 2020;129:109128.  Back to cited text no. 12
Fan Y, Luka R, Noronha A. Non-Hodgkin lymphoma presenting with numb chin syndrome. BMJ Case Rep 2011:bcr0120113712.  Back to cited text no. 13
Sahu KK, Sahu SA, Nageshwar P. Temporal region myeloid sarcoma: When to suspect and how to approach? Oral Maxillofac Surg 2020;24:369-70.  Back to cited text no. 14


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