An unusual tuberculosis case presentation as cervical lymphadenopathy and extensive pelvic and peritoneal lesions

Sio-pan Chan 陳少斌

HK Pract 2024;46:9-11

Summary

A young lady presented with a progressively enlarging cervical mass. The initial diagnosis was tuberculous lymphadenopathy. However, her blood tests revealed a very high level of CA125. Subsequent investigations and imaging raised the suspicion of adnexal tumour with peritoneal metastasis. Successful treatment of tuberculosis (TB) has cleared her infection leading to a complete resolution of the cervical lymphadenopathy and all the adnexal and peritoneal lesions.

摘要

梅毒跟結核病同稱是診斷中兩種最大的“模仿者”， 因他都可以模仿任何其他病的病徵。現在梅毒已經相對少 見，但是結核病在香港每年都有數千案例。家庭醫生不時 都會遇到結核病，一般多數在照肺時發現，但有時會遇到 一些不尋常的病徵。本文是報告一個比較少有的結核症， 其徵狀與抗散性的卵巢瘤極為相似，需要格外小心以避免 悲劇性的醫療錯誤。

Introduction

After syphilis, tuberculosis (TB) is known as the second great imitator of diseases.¹ While syphilis is now rarely seen in private practice, tuberculosis is still a relatively common disease in our society. TB should always be considered in the differential diagnoses in patients with unusual clinical presentations. A case of tuberculosis presented as cervical lymphadenopathy with adnexal and peritoneal involvement is discussed.

The Case Presentation

History

The patient was a 20-year-old female student who had noticed a gradually enlarging mass in her right upper neck for a couple of weeks. The mass was not painful, and she did not experience any systemic symptoms. She had also noticed some weight loss in the preceding few months. Additionally, she was undergoing an orthodontic procedure that had been causing her pain while biting. She attributed the cause of her weight loss to the pain when eating solid food, as she had been on a soft diet for a few months. At the same time, she was very stressed preparing for her Hong Kong Diploma of Secondary Education Examination. Her menstruation was regular, and she did not have any sleeping problems, fever, or night sweats.

Physical examination

On physical examination, her general condition was satisfactory. She was fully alert and energetic. There was no pallor. She was markedly underweight at 46.5kg with BMI of only 15.2 (according to the patient, she has been quite thin all along). There was a firm mass in the upper right posterior triangle of her neck approximated 3cm in diameter. The mass was slightly mobile and mildly tender. The other physical findings were unremarkable. The abdomen was normal with no abnormal mass felt nor ascites detected.

Investigation

A chest X-ray, a full blood workout (which had included a panel of tumour markers, as nasopharyngeal carcinoma was one of the differential diagnoses). An ultrasound scan and fine needle aspirate (FNA) for cytology were performed. The chest X-ray report was normal. Ultrasound scan revealed multiple well defined oval hypoechoic lesions measuring up to 3cm. The FNA cytology was suggestive of tuberculosis showing granulomatous inflammation and Langhans giant cells. Acid-fast bacilli (AFB) were not demonstrated.

Blood investigation showed there was no anaemia, the ESR was elevated at 33mm/hr. The WBC count was normal but the WBC differential showed a lowish lymphocytes of 18.1%. QuantiFERON-TB Gold (QFT) was positive but this test was not specific enough for a definitive diagnosis. The other significant finding was a markedly elevated CA 125 of 537 U/ml. Incidentally, her serum 25 (OH) Vitamin D was very low at 10.1 ng/ml. The author routinely checks for baseline vitamin D level in most patients presenting with unusual clinical features.

Because of the significantly elevated CA125, a pelvic ultrasound scan was performed. The report revealed lobulated hypoechoic masses at bilateral adnexa "worrisome of matted lymphadenopathies or peritoneal neoplasms". The radiologist recommended correlation with PET-CT in view of the high CA125. Her CA 125 was rechecked before the PET-CT and it went up to 806U/ml.

The PET-CT came back with the findings of hypermetabolic bilateral adnexal masses and multiple peritoneal lesions, with the remark "more suggestive of widespread metastases than tuberculosis" made by the radiologist. There was a chain of hypermetabolic right cervical nodes in keeping with the FNA finding of TB cervical nodal involvement. Incidentally, there was a cluster of hypermetabolic left axillary nodes which are likely to be related to her recent COVID vaccine injection in the left arm. Two gynaecologists were consulted during this time and their opinions were split on whether the pelvic and peritoneal lesions were due to a gynaecological pathology.

Given such findings, a peritoneal biopsy on one of the "hot" nodules was performed by an interventional radiologist. The subsequent pathology showed fibrous tissue with granulomatous inflammation, occasional multinucleated giant cells and lymphoplasmacytic infiltrates. Focal caseous necrosis was seen. Ziehl– Neelsen stain was negative for AFB. There was no evidence of malignancy.

Treatment and Progress

All the investigation results strongly suggested tuberculous infection, pending culture report. She was started on standard anti-tuberculous treatment with 4 drugs including Ramfipacin, INAH, pyrazinamide, ethambutol for 2 months, then continued on Rifampicin and INAH for another ten months.² On top of her standard anti-tuberculous drug, vitamin D supplement 5000 IU/day was given throughout the whole period of treatment. A prolonged treatment up to a year was indicated because of a higher chance of recurrence for extrapulmonary TB lymph node involvement.² After two months of anti-TB treatment. The patient was doing well, the neck mass got significantly smaller in size. Her ESR has returned to normal. Her CA125 has dropped to 95 U/ml. She started to regain weight. Liver/renal function tests, visual test and colour blindness test were all normal. One year after treatment, her cervical lymph nodes had returned to normal size and ultrasound scan showed complete resolution of the adnexal and peritoneal masses and all blood tests had returned to normal.

Discussion

Tuberculosis is the 13^th leading cause of death and is the 2^nd leading infectious killer after COVID-19.³ According to the Centre for Health Protection, Hong Kong has on average 4000 TB cases per year, most of which were pulmonary in origin, approximately 20% are extrapulmonary TB.³ General practitioners are expected to see tuberculosis cases once in a while. A high index of suspicion is necessary in encountering patients with unusual clinical presentations. In the author’s experience, most TB cases are manageable in the general practice setting. TB is a notifiable disease, once a diagnosis is confirmed, the Departure of Health must be duly notified. The physician should comply with all the necessary treatment and surveillance of contacts as per required by the Department of Health (DH). The DH will regularly contact the physician in charge and monitor the progress until the patient is fully recovered.

The particular point of interest in this case is the finding of an unusually elevated CA125 that was way higher than ordinary peritoneal irritation, which is usually around 100U/ml.^4,5 The diagnostic images from ultrasound scan to PET-CT only added the suspicion of a co-existing gynaecological neoplasm. PET-CT cannot distinguish active tuberculosis from neoplastic lesions,⁶ it only helped to locate a suitable lesion for biopsy. The ultrasound guided peritoneal biopsy gave the most definitive guide on subsequent management.

There are numerous case reports from the literature that unnecessary operations were performed for ovarian tuberculosis with disastrous consequences, many of such mistakes occurred for the African immigrants living in Europe.⁷ Perhaps this patient was lucky that she did not present with any gynaecological problems. From hindsight, if a full blood workout had not been performed and the patient was just treated as a simple case of TB lymphadenopathy, she would recover equally well without even knowing she has got severe peritoneal and pelvic involvement. Here we are facing a dilemma between missing an important diagnosis or over-investigation resulting in unnecessary anxiety and financial burden.

Finally, it was noted that this patient had a very low serum 25 (OH) vitamin D level of 10.1ng/ml. The National Institute of Health regards a serum level of < 20 ng/ml while other authorities consider < 30ng/ml as insufficient. Tuberculous infection has a very strong correlation with vitamin D deficiency.⁸ Therefore, Vitamin D supplement was given to the patient on top of the standard anti-TB treatment. Furthermore, during the COVID-19 pandemic, many published papers have shown the importance of vitamin D in the health of our innate immune system and its role as an immune moderator to reduce cytokine storms,⁹ which is outside the scope of this case report.

References

1. Sujata Jetley, Zeeba S Jairajpuri, Mukta Pujani, et al. Tuberculosis 'The Great Imitator': A usual disease with unusual presentations. Indian J Tuberc. 2017 Jan;64(1):54-59. doi: 10.1016/j.ijtb.2016.01.001.
2. Centre for Health Protection Guidelines- tuberculosis. Available from: https://www.chp.gov.hk/en/healthprofessionals/30/index.html
3. Annual report of TB & Chest Service, 2020 Annual Report, Department of Health.
4. Bal Katipoglu, Ekrem Basara, Ihsan Ates, et al. A Case Report of Peritoneal Tuberculosis: A Challenging diagnosis. Case Rep Infect Dis. 2018 Jan 11;2018:4970836. doi: 10.1155/2018/4970836.
5. Ichiki H, Shishido M, Nishitani K, et al. Evaluation of CEA, SLX and CA125 in active pulmonary tuberculosis. Nihon Kyobu Shikkan Gakkai Zasshi. 1993 Dec;31(12):1522-1527.
6. Wei-Ye Yu, Pu-Xuan Lu, Majid Assadi, et al. Updates on 18 F-FDG-PET/ CT as a clinical tool for tuberculosis evaluation and therapeutic monitoring. Quant Imaging Med Surg. 2019 Jun; 9(6): 1132–1146. doi: 10.21037/ qims.2019.05.24
7. Malihe Hasanzadeh, Hamid Reza Naderi, Azamossadat Hoseine Hoshyar, et al. Female genital tract tuberculosis presenting as ovarian cancer. J Res Med Sci. 2014 Feb; 19(2): 184–189.
8. Aliasghar Farazi, Farshideh Didgar, Aghmorad Sarafraz. The effect of vitamin D on clinical outcomes in tuberculosis. Egyptian. Journal of Chest Diseases and Tuberculosis. 2017 July; 66(3):419-423.
9. Bilezikian JP et al, Mechanism in Endocrinology: Vitamin D and COVID-19. Eur J Endocrinol. 2020 Nov;183(5):R133-R147. doi: 10.1530/EJE-20-0665.