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  Table of Contents  
Year : 2021  |  Volume : 58  |  Issue : 3  |  Page : 437-440

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

Department of Radiology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India

Date of Submission20-Apr-2020
Date of Decision03-May-2020
Date of Acceptance20-Jun-2020
Date of Web Publication02-Jul-2021

Correspondence Address:
Shilpa Sankhe
Department of Radiology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijc.IJC_364_20

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 » Abstract 

Numb chin syndrome (NCS) is a rare presentation of primary or recurrent malignant neoplasms among other non-neoplastic causes. The syndrome is characterized by altered sensations in the distribution of the mental nerve and presents with pain and paresthesias along the distribution of the inferior alveolar nerve and its branches. The primary diagnosis is indicated while following up patients through positron emission tomography/computed tomography (PET/CT) when a hypermetabolic focus is seen in the vicinity of the angle of the mandible. Further anatomical localization is performed using magnetic resonance (MR) neurography and postcontrast MR imaging, which demonstrates neural involvement. We hereby describe a case of a 56-year-old man, a treated case of DLBCL (diffuse large B-cell lymphoma), presenting with NCS and diagnosed with perineural invasion through PET/CT and further MR evaluation. To our knowledge, there are no other reports in the literature describing the MR neurography appearance of the inferior alveolar nerve in NCS. We hereby stress on the use of MR neurography followed by postcontrast 3D sequences with multiplanar reformatting for adequate lesion detection.

Keywords: Inferior alveolar nerve, neurography, numb chin syndrome, perineural

How to cite this article:
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 2021;58:437-40

How to cite this URL:
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 [serial online] 2021 [cited 2022 May 17];58:437-40. Available from:

 » Introduction Top

Numb chin syndrome (NCS) refers to symptoms of numbness and paresthesias in the distribution of the mental nerve. In the absence of dental symptoms, this is considered indicative of a malignant neoplasm. In a few cases that have been reported, NCS was the first presentation of an underlying neoplasm, whereas others stated it as a symptom of relapse.[1] The role of positron emission tomography/computed tomography (PET/CT) has broadened in the recent years, due to widespread availability and better experience with use. PET offers a functional component to the diagnosis, by indirectly evaluating the amount of glucose uptake, which serves as marker of tumor proliferation. The fusion of PET with CT offers greater anatomic accuracy. Magnetic resonance imaging (MRI) adds to the available information by better anatomic localization, as it has a greater spatial resolution.

In the case that we present, NCS was a symptom of relapse of disease, in a known treated case of diffuse large B-cell lymphoma (DLBCL). The diagnosis was made on PET/CT followed by magnetic resonance (MR) neurography of the inferior alveolar nerve (IAN) along with 3D postcontrast imaging.

 » Case Report Top

A 56-year-old man presented with complaints of numbness, tingling sensation, and pain in the left side of jaw for 2 months. He also had numbness in the left lower lip and chin region. There was no history of any surgery or tooth extraction. The patient was not diabetic. He was a treated case of testicular lymphoma. The first PET/CT done for the staging of the disease 1.5 years back had shown widespread dissemination of the disease, with the involvement of bilateral testes, myocardium, peritoneal deposits and mesenteric lymph nodes, lung, and renal cortex. B symptoms were present at the time of initial diagnosis in the form of significant weight loss of 12 kg over a period of 3 months and fever with night sweats for 2 months. The stage of the disease at the time of the initial diagnosis was Stage IVBX. Serum lactate dehydrogenase (LDH) at the time of initial diagnosis was 220 IU/L (reference value of 110–190 IU/L). Bone marrow examination and cerebrospinal fluid (CSF) examination at that time were negative for malignant infiltration. The patient was given four cycles of chemotherapy (EPOCH Regimen—etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride). Orchiectomy was not performed in our patient as there was bilateral testicular and systemic spread of the disease. An interim PET/CT done a year back revealed complete metabolic resolution of the disease with no new lesions. The patient further went on to receive two cycles of chemotherapy (EPOCH) followed by radiotherapy to testes. Six months later, the patient presented to the hospital with complaints of headache and backache. A repeat PET/CT was performed to look for recurrent disease. The scan showed [Figure 1]a and [Figure 1]b focal FDG (18-fluorodeoxyglucose) uptake in the soft tissue anterior to the left submandibular gland. The lesion measured 1 cm in the short axis and had a standardized uptake value (SUV max) of 12.71. No lytic lesion or obvious inferior alveolar canal widening was seen on the CT counterpart. Apart from this, multiple other lesions were also seen in both adrenal glands and paravertebral region. The patient was then referred to radiology for the exact localization of the lesion. In the meanwhile, new symptoms of numbness and pain in the left side of jaw appeared, raising a red flag for IAN involvement by the disease.

MRI of the maxillofacial region was then performed, along with a neurography of the left IAN. The T2 SPACE MR neurography sequence showed a hyperintense soft tissue [Figure 2]a adjacent to the inferior alveolar foramen on the left side. Multiplanar reconstruction (MPR) in the axis of the IAN showed thickening of the left IAN with adjacent soft tissue. T2 SPACE MPR image of the right IAN was done for comparison [Figure 2]b. Contrast study was performed using 8 ml of gadolinium DTPA and postcontrast 3D VIBE (volume interpolated breath-hold examination). MPR images showed an abnormal thickened and enhancing left IAN with adjacent soft tissue [Figure 2]c. The normal right IAN has been shown for comparison [Figure 2]d.
Figure 1: Axial FDG PET (18-fluorodeoxyglucose Positron Emission Tomography) (a) and fused PET/CT (Positron Emission Tomography/Computed Tomography) (b) images of the neck showing increased uptake in soft tissue adjacent to ramus of mandible on the left side (blue arrow). SUVmax (maximum standardized Uptake Value) measured 12.71. The normal physiological uptake of the palatine tonsil is marked with an asterisk (*)

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Figure 2: MRI neurography T2 SPACE on the left side (a) shows thickening and hyperintensity along the left IAN (green arrow). The normal right IAN (b) is shown for comparison (green arrow). Reformatted GRE postcontrast VIBE sequences on the left side (c) show thickening and enhancement of the left IAN (black arrow) with associated soft tissue adjacent to the proximal inferior alveolar canal. The normal right IAN (d) has been shown for comparison (black arrow)

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On combining the clinical, PET/CT, and MRI findings, a diagnosis of NCS secondary to lymphomatous perineural spread in a treated case of DLBCL of testis, suggestive of tumor relapse was made. Serum LDH at this point in the disease was 160 IU/L. CSF examination was negative for malignant cells. The patient was offered an autologous stem-cell transplantation but declined due to financial constraints and was then started on salvage chemotherapy with oral lenalidomide and dexamethasone. The patient is on regular follow-up at the time this case report is being written.

 » Discussion Top

NCS, also known as mental nerve neuropathy, represents a collection of symptoms of paresthesias, sensory loss, and rarely pain along the distribution of the mental nerve. Mental nerve is a termination of the IAN, which innervates the skin of the chin, oral mucosa, and lower lip on each side.[2] NCS is more commonly unilateral,[3] with no specific side predilection although bilateral NCS as an entity has also been described.[4] It is a clinical manifestation of malignant disease or its recurrence in almost 47% of the cases.[5] Certain tumors of the head and neck region use nerves as a conduit for their spread, which increases the risk of recurrent and metastatic disease. Perineural invasion is a histologic term, which cannot be deciphered on currently available imaging modalities, whereas perineural spread refers to the dissemination of the tumor along a nerve which can be detected on imaging.[6] Common nerves involved in the perineural spread include the trigeminal and facial nerves. Apart from the head and neck neoplasms that may locally extend to the nerve and spread along them, breast cancer and lymphoma are the most frequently associated malignant neoplasms.[7] Other conditions that may cause symptoms of NCS include benign and malignant neoplasms of the inferior alveolar/mandibular nerves, bone tumors (osteosarcoma), and systemic infiltrative disorders like sarcoidosis, amyloidosis, and non-Hodgkin lymphoma (NHL).[8] Nearly 40% of all NHLs are extranodal, the most common histologic subtype being DLBCL. Common sites of involvement in DLBCL are the Waldeyer ring, but it can also involve the bone and soft tissue of the jaw.[9] A few rare case reports[10],[11] describe NCS as the first manifestation of relapse of DLBCL, which was the case with our patient.

Imaging modalities for the evaluation of NCS include PET/CT for detection, followed by MRI for better anatomic localization. Focal or linear increased FDG uptake along the V2 division of the trigeminal nerve or medial surface of the mandible, asymmetric activity in the masticator space, foramen ovale, and Meckel's cave are indicators of perineural spread of disease. In head and neck tumors, PET/CT is 95–96% sensitive and 60–72% specific for detection of recurrence.[12] In our case, the patient presented with pain and paresthesias in the left lower lip, angle of mouth, and chin. Pain is an uncommon presentation of NCS[13] and presumably arises due to tumor compression of the sensory fibers.

When correlating FDG PET/CT features with MR imaging, there is a need to look for direct and indirect signs. Direct signs include prominence, irregularity, and asymmetric enhancement of the nerve. Indirect signs include signs of denervation muscle injury. In our case, unilateral soft tissue with enhancement and thickening was seen along the IAN. Since the IAN gives no motor branches once within the mandibular canal, no motor involvement was expected, which was also the case in our patient.

According to a systematic review of sixteen studies and 136 cases by Galan Gil et al.,[7] the mean age for patients with malignant causes of NCS was 47.8 years, with a propensity for females and unilateral involvement. Our patient was a 56-year-old man with unilateral symptoms. According to a study by Vadell et al., NCS was the first sign of neoplastic relapse in 100% of his cases.[14]

The pathophysiology of NCS in cancer patients is largely unknown. Metastasis to bone marrow and infiltration of the jaw and then the nerve may be a mechanism in hematological malignancies and breast cancer. Direct perineural invasion is common in squamous cell carcinomas, lymphoma, and tumors of the IAN.[1] Another described mechanism is ischemia and subsequent nerve damage secondary to inflammation caused by the malignancy.

Pitfalls in imaging include the insensitivity of PET/CT to detect active lesions smaller than 1 cm in size in absence of significantly increased FDG uptake. Small nerve branches, which may be involved by tumor, may not be picked up on PET/CT due to this reason.[15]

In summary, the diagnosis of NCS is essentially clinical. Imaging is helpful in confirming the diagnosis and exact localization and appropriate treatment planning. PET/CT followed by MR neurography and contrast MR studies is helpful for detection and localization of the lesion, as well as the distribution of the disease.

3D postcontrast study with isotropic voxel (VIBE in our case) and further multiplanar reconstruction along the associated nerve pathways helps to successfully demonstrate perineural invasion.

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.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


 » References Top

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. 1
Laurencet FM, Anchisi S, Tullen E, Dietrich PY. Mental neuropathy: Report of five cases and review of the literature. Crit Rev Oncol Hematol 2000;34:71-9.  Back to cited text no. 2
Colella G, Giudice A, Falcone U, Siniscalchi G, 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. 3
Algahtani H, Shirah B, Bassuni W, Adas R. Bilateral numb chin syndrome as the initial presentation of Burkitt's lymphoma/leukemia: A report of two cases and review of the literature. Case Rep Hematol 2016;2016:3791045.  Back to cited text no. 4
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. 5
Ginsberg LE. Imaging of perineural tumor spread in head and neck cancer. Semin Ultrasound CT MR 1999;20:175-86.  Back to cited text no. 6
Galán SG, Peñarrocha MD. Malignant mental nerve neuropathy: Systematic review. Med Oral Patol Oral Cir Bucal 2008;13:16-21.  Back to cited text no. 7
Turner-Iannacci A, Mozaffari E, Stoopler ET. Mental nerve neuropathy: Case report and review. CJEM 2003;5:259-62.  Back to cited text no. 8
Triantafillidou K, Dimitrakopoulos J, Iordanidis F, Gkagkalis A. Extranodal non-Hodgkin lymphomas of the oral cavity and maxillofacial region: A clinical study of 58 cases and review of the literature. J Oral Maxillofac Surg 2012;70:2776-85.  Back to cited text no. 9
Balamurugan N, Arathisenthil SV, Senthilkumaran S, Thirumalaikolundusubramanian P. Numb chin syndrome: A harbinger of tumor progression or relapse. Am J Emerg Med 2017;35:805.e1-e2.  Back to cited text no. 10
Barrett AP. Selective anesthesias of the inferior alveolar nerve in leukemia and lymphoma. J Maxillofac Oral Surg 1985;43:992-4.  Back to cited text no. 11
Wong RJ, Lin DT, Schoder H, Patel SG, Gonen M, Wolden S, et al. Diagnostic and prognostic value of [(18)F] fluorodeoxyglucose positron emission tomography for recurrent head and neck squamous cell carcinoma. J Clin Oncol 2002;20:4199-208.  Back to cited text no. 12
Massey EW, Moore J, Schold SC. Mental neuropathy from systemic cancer. Neurology 1981;31:1277-81.  Back to cited text no. 13
Vadell CN, de Bes Tusquets IT, Roquer JG, Corominas JT, Nogué MA, Gil MG, et al. Neuropathy of the chin associated with neoplasms. Presentation of 5 cases and a review of the literature. Arch Neurobiol (Madr) 1989;52:17-22.  Back to cited text no. 14
Fukui MB, Blodgett TM, Snyderman CH, Johnson JJ, Myers EN, Townsend DW, et al. Combined PET-CT in the head and neck: Part 2. Diagnostic uses and pitfalls of oncologic imaging. Radiographics 2005;25:913-30.  Back to cited text no. 15

Please see the related commentary [Jandial A, Sahu KK. Not just the tip of the iceberg: Commentary on Numb Chin syndrome. Indian J Cancer 2021;58:473-5]


  [Figure 1], [Figure 2]


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