Squamous Cell Carcinoma of Left Lateral Border of Tongue followed by Therapy Induced Mucositis Grade 4

Review Article

Squamous Cell Carcinoma of Left Lateral Border of Tongue followed by Therapy Induced Mucositis Grade 4

  • Mayank Virmani 1
  • Mandeep Kaur 2*

*Corresponding Author: Mandeep Kaur, B.Pharm, Pharm.D, Assistant professor, Department of Pharmacy Practice, ISF College of Pharmacy, Moga, Punjab, India 142001

Citation: Mayank Virmani , Mandeep Kaur.(2022). Squamous Cell Carcinoma of Left Lateral Border of Tongue followed by Therapy Induced Mucositis Grade 4; Journal of Clinical Case Reports and Studies 3(9); DOI: 10.31579/2690-8808/133

Copyright: © 2022 Mandeep Kaur, This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: 24 May 2022 | Accepted: 02 June 2022 | Published: 10 October 2022

Keywords: OSSC; EBRT; RIOM; chemotheraputic agents; gray

Abstract

Carcinomas are the major serious health issue in today’s healthcare system.  while its prognosis is difficult at earlier stages. OSSC oral squamous cell carcinomas are reported more than 3 lakhs new cases world-wide and it is sixth most common cancer world-wide. Squamous cell carcinoma is defined as the cancer of soft, flat, thin squamous cells mainly affect the soft cell regions like tongue diagnosed by various investigational imaging and biochemistry parameters. In this case patient was diagnosed with High Grade Squamous Cell Carcinoma. Radiation therapy along with chemotherapy is the option for better therapeutic outcomes. Hence, EBRT therapy is given and in 2 gray every cycle and a total of 59.8 gray, 20 cycle therapy depending on condition of patient. In 90% cases radiation therapy leads to RIOM (Radiation Induced Oral Mucositis) which is totally unprotectable and there in no specific treatment option available in market approved by US-FDA yet. RIOM is diagnosed by WHO grading system based on the parameters and observations. In this condition patient suffers from inflammation, mouth ulcers and progressive condition and patient can not be able to swallow anything. It’s five stage process which treated by giving antibiotic in case of RIOM and oral hygenine, mouthpaints are advised. Levofloxaccin 750mg with clotrimazole mouthpaint was given to the patient. Radiation therapy continued with curative and Supportive therapy and was successful radiation therapy also shows good response and reduction in growth of tumor was observed and therapeutic goals were achieved.

Introduction

Carcinoma is the term defines cancer occurring in cell, skinline or organ with soft tissues. Various types of cancer growth have been seen in the tongue, but the most common type is squamous cell carcinoma, Squamous cells are thin, flat cells that line the mouth and other organs. Oral cancer is found to be the sixth most common cancer worldwide. Approximately 300,373 new cases of oral squamous cell carcinoma (OSCC) are annually reported around the world[1-2],It typically occurs in elderly men during the fifth-eighth decade of life[3] .  In 1976 two scientists Krolls and Hoffman analyzed 14,253 cases of squamous cell carcinoma of the oral soft tissues and found that  35.2% of the intra-oral lesions were observed only on the tongue [4].   In India, Oral carcinoma has become a major health problem mainly due to the high prevalence of smokeless tobacco use. There are two types of tongue cancer: 

  • Cancer of the oral tongue: The front two-thirds of the tongue region that you stick out is called the oral tongue. 
  • Cancer of the base tongue: The base is the back one-third of the tongue region extends down the throat.

Through Grades we can  identify the severity of cancer growing in the mouth and are as follows. There are 3 grades of mouth Cancer[5]:

  • Grade 1 (low grade)  cancer cells look exactly like normal mouth cells
  • Grade 2 (intermediate grade) slightly different in comparison to normal mouth cells
  • Grade 3(high grade) is very abnormal-looking and not much like normal mouth cells.

Patient was suffering from squamous cell carcinoma and External Beam Radiation Therapy was given to treat but unexpextedly, Radiation therapy leads to  RIOM as its adverse effect .

RIOM (Radiation-Induced Oral Mucositis) is one of the major ionizing radiation toxicities defined as an injury of tissues caused by radiation/radiotherapy (RT), Eventually marked adverse effects on patient quality of life and continuity of cancer therapy [6].  In the United States, its economic cost was approximately to achieve  17,000.00 USD per patient with head and neck cancers. Varies between 7 to 98 days. . RIOM of grades 3 and 4 have been observed in 56% of head and neck cancer patients treated with radiotherapy[6-7]. While risk factors are [8]:-

  • Smoking
  • Bad oral hygiene
  • Tobacco Chewing
  • Nutritional Deficiency
  • Tissue Injury

WHO has designed grading system for stating severity stage of oral mucositis which is as follows:-

The WHO Grading system for Oral mucositis[9] 

  • Grade 0-No mucositis present
  • Grade 1-Irritation of Oral mucosa, with pain no overt ulceration patient has a normal diet
  • Grade 2-Sore evident in oral mucosa, the patient still able to swallow solid food
  • Grade 3-Patient experiences sensitivity when swallowing solid food, a liquid diet is necessary
  • Grade 4-Patient unable to swallow total parenteral nutrition or tube feeding is necessary

Mucositis uplift stage by stage and various worsten changes observed as it converted to higher stage followed by healing at last stage which are as follows:-

Developmental Stages Of  Mucositis [10]

In 2004, Sonis, a Scientist  suggested five stages of Oral Mucositis:-

  • Stage 1– (Initiation): At this stage lesions were formed directly,  occurs due to chemotherapy or irradiation as well as negatively affect the cells along with the strands of DNA in the basal epithelium and the submucosa. Fformation of ree radicals are reactive oxygen species (ROS) also occurs and acts an interfering role in the biological event of the later stage [10].
  • Stage 2- (Upregulating): It shows an adverse effect on DNA, ROS, and cells  which starts a chain of reactions whoch produces pro-inflammatory cytokines IL 1-B& TNF-Alpha from resident cells resulting in increased vascular permeability and infiltration of the cell. They work by stimulating pathways leading to the formation of lesions or the death of basal cells by the process of apoptosis [11]. NF-B is the sole pathway leading to the cause of normal apoptosis [12].
  • Stage 3- (Signal amplification): The release of pro-inflammatory cytokines not only damages the cells but also provides positive feedback which amplifies the lesions caused directly by radiation or chemotherapy by the pathway including nitrogen metabolism and other pathways. TNFALPHA- is a very potent activator of several pathways that results in tissue injury, which includes ceramide and caspase pathways and the transcription pathway mediated by NF-kB. In this process, tissue is altered biologically but its appearance remains the same [12].
  • Stage 4- (Ulceration): This stage is characterized by painful lesions subject to colonization by bacterial proliferation, causes new tissue damage, and activates the production and release of additional pro-inflammatory cytokines by infiltrating mononuclear cells. During this Phase, Basement membrane protective barrier is lost and inflammation in the mucosal barrier is observed. Three-way mechanism followed by triggering of Oxidating stress, mediation by active  T-cells, and finally preceded by the formation of adhesion molecules. Bacterial colonization also takes place by gram-positive, gram-negative, and anaerobic micro-organisms, and bacterial cell wall mediated products damage the local tissue and amplify injury stage later have a high risk of bacteriemia and sepsis[12].
  • Stage 5- (Healing): This phase is characterized by epithelial proliferation as well as cellular and tissue differentiation. Thus restoring the integrity of the epithelium. Starts with extracellular matrix signaling In which proliferation, migration, and differentiation of basal epithelial cells are observed [11], Leucocyte recovery and oral mucosa seem to be normal. But the patient is at an increased risk of re-occurrence.

Case Summary:

A 54 years old male patient was admitted in cancer department having complaints of tongue bite while taking meal in afternoon. After 2 days   unbearable inflammation  and pain at the site of the bite.  After some time a sore formation takes place at the left lateral border of the tongue and the patient started following home remedies to cure it. But there's no satisfactory improvement and it was continuously causing discomfort to the patient and condition to become more worsen than earlier. After that patient starts facing difficulty in swallowing and eating food and was not feeling well while talking and sleeping and eating. Afterward, the patient feels much pain and inflammation in the affected region of the tongue. Patient-reported to the hospital and was admitted to Hematology/Oncology department. All the physical examinations, and possible investigations were done. The sore formation that had taken place earlier was converted into a tumor on the left lateral side of the tongue downward basal and identifications were done and were found to be Squamous Cell Carcinoma of Tongue. Socioeconomically patient is non-smoker and follows a vegetarian diet. There is no history of allergy or no previous medication history. After all the investigations ( Table 1), a drug regimen was designed and a follow-up was started (Table 2). The patient was later on drugs and Radiation therapy was started. But on the 6th radiation Cycle patient complained about oral sores and difficulty in swallowing liquid and eating a semi-solid diet. Physical examination was done and on the behalf of investigations itwas confirmed that the patient was suffering from Radiation-induced oral mucositis (RIOM), Grade 4 stage.  Radiation therapy cycles were continued, and along with it Supportive therapy for the same was designed and started at that time. Later, After 3 days patient observe a reduction in oral sores and was able to take some liquid diet.

                    Figure 1 -Image Showing The affected area diagrammatically, Source:- Internet 

Investigations

Biopsy 

  • Hemiglossectomy(Surgical removal of part of the tongue) and Neck dissection are Done to remove and further investigate outgrowth tumor 
  • 3 gray brown soft tissue pieces altogether of size (0.4*0.3*o.8 cm) and Block  (biopsy specimen is put in a container with a mixture of water and formaldehyde (formalin) or some other fluid to preserve it) And testing is done 
  • After Examination Results are:- High-grade Carcinoma With Squamous Diffraction favor High-Grade Squamous Cell Carcinoma.
  • Deep Study Indicates 
  • H&E Section Hyperkeratanized Squamous Epithelium and Nest Of Polygonal Cells.
  • Have a moderate amount of acute granular cytoplasm, Irregular Hyperchromatic Nuclei with pleomorphism.
  • Ulcer formation takes place. And Lymphatic Node Present
  • Both Epiglottis were normal In size
  • The vocal cord appears normal
  • Salivary gland normal
  • Pyriform sinus and Aryepiglottic fold appear normal
  • Hyoid bone unrenewable
  • Neoplasticity at the Lateral side of the Anterior tongue was seen.

Laboratory Investigations:-

Table1: Laboratory findings of the Patient

Microcystosis and Hypochromia observed

Microcytosis is a blood disorder in which the mean blood cellular volume becomes less than 82 μm3 (82 fL) in adults.

Hypochromia means that the red blood cells have less color than normal when examined under a microscope.

Decreased level of lymphocytes stated that it is due to the known adverse effect of radiation therapy. Many researchers have also stated that(13). 

Treatment and Management 

Radiotherapy 20 Cycles Advised :-  EBRT (External Beam Radiation 

 

Therapy) was given To treat Tongue Cancer (Squamous Cell Carcinoma).

After 6 Cycles  Adverse effect of Mucositis grade 3 following grade 4 was observed. The patient was apparently on a semisolid diet 

Due to mouth ripe patient was not able to swallow .

Pt was advised to take oral care as :- 

  • Candid B Mouth paint (CLOTRIMAZOLE-1%W/V)
  • Glycerine 
  • Advised to take Plenty of fluids -4l /day
  • B-ringer gargles
  • Steam Inhalation

Table2: Indicating Patients Drug Regimen

Same treatment follow-up for the next 3 days was given to the patient. While the Patient was on treatment on its 6Th radiation cycle he observed some difficulties like mouth ripe Which were later confirmed as Mucositis a major adverse effect of Radiation Therapy.

Discussion

According to studies Approximately 90% of confirmed malignant tumors diagnosed in the oral cavity are Oral Squamous Cell Carcinomas, especially in the tongue, and affect mostly men rather than women[1] . Same in this  case a 54 years old male patient was affected and the study also shows a high risk of recurrence of Tumor[1]. Biopsy reports confirmed high-grade squamous cell carcinoma of the lateral region of the tongue. But the patient is quite responsive and in the positive recovery phase.  Studies revealed that RIOM occurs in 100% of altered fractionation radiotherapy head and neck cancer patients and cant be protectable lasts between 7-98 days and causes inflammation in the tongue, mucosa, and pharynx[7]. Exactly the same was seen inpatient as the patient was complaining of sores, and was not able to swallow/intake food. Antibiotics are necessary for treatment so antibiotics were prescribed for cure Levofloxacin 750 mg was administered and clotrimazole mouth paint was advised for application to the affected region. No single therapeutic agent has been approved by the US FDA for the treatment of RIOM so random supportive therapy is prescribed for treatment. The patient shows improvement in the condition and for the next three days, the same therapy was continued with radiation therapy for cancer.

Conclusion

The patient is responsive and has a good recovery record with both the conditions Squamous cell carcinoma and RIOM with the treatment plan designed for both the problems. Oral hygiene was highly focused on administering Drug a designed drug regimen at accurate doses, Nutrition is also maintained as the patient was not able to swallow solid and semi-solid diet. Radiation therapy continued even after adverse effects because there is no other successful treatment option for the squamous cell carcinoma later when the patient complained of discomfort supportive treatment was designed and successful therapeutic goals were achieved. Radiation therapy shows a good response in reducing carcinoma growth.

References

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