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Vol. 4. Núm. 2.
Páginas 1-50 (abril - junio 2022)
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Vol. 4. Núm. 2.
Páginas 1-50 (abril - junio 2022)
Scientific letter
Open Access
Incidence of Cancer in Sarcoidosis Patients in a Tertiary Care Hospital in the UK
Incidencia de cáncer en una cohorte de pacientes con sarcoidosis de un hospital terciario en Reino Unido
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Sonia Mannan, Beatriz Lara
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beatriz.lara@uhcw.nhs.uk

Corresponding author.
Respiratory Medicine, Coventry&Warwickshire University Hospitals NHS Trust, Clifford Bridge Road, Coventry CV2 2DX, Warwickshire, United Kingdom
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Dear Editor,

Sarcoidosis is a multisystem chronic granulomatous inflammatory condition of unknown aetiology. It can affect almost any organ of the body. Over 90% cases, most commonly lung, including thoracic lymph nodes and/or parenchymal involvement occur.1 Increased risk of cancer in sarcoidosis is a long-debated issue over half a century. It has been postulated that chronic inflammation and/or different immunological dysregulation in sarcoidosis may be associated with high risk of cancer incidence.2,3 Few population-based study also revealed increased incidence of cancer in sarcoid patients.4,5 Though the possibility of misclassification and selection bias cannot be excluded.6 Series of case study found high incidence of lymphoproliferative disease7 and lung cancer8 in sarcoid patients; however, case report is inconclusive to establish any association.

We aim to confirm if incidence in our cohort and profile of cancer is similar to previous studies. We conducted a retrospective descriptive study, using individual patient's unique hospital number from the online intranet-based record system, of a cohort of sarcoidosis patients attending to Coventry University Hospital from 2002 to July 2021.

This study achieves the ethical requirements of retrospective descriptive studies where the data have been used anonymously.

The study group consist of 121 pulmonary sarcoidosis patients seen in a respiratory outpatient clinic at University Hospital Coventry & Warwickshire over the period of Jan 2002 to July 2021. Among these 121 patients 39 (32%) have extra-pulmonary involvement as well. 79 patients (65%) had histologically proven diagnosis of sarcoidosis. Table 1 shows the characteristics of the study population.

Table 1.

Characteristics of sarcoidosis patients.

Variable  N 
Total sarcoidosis patients  121 
Sex
Male  53 (44%) 
Female  68 (56%) 
Age of diagnosisa
20–39  33 (27%) 
40–59  63 (52%) 
≥60  24 (20%) 
Radiological stage during diagnosis
0-I  75 (62%) 
II  23 (19%) 
III  3 (3%) 
IV  2 (2%) 
No record  18 (15%) 
Smoking history
Current smoker  20 (16.5%) 
Ex-smoker  28 (23%) 
Never smoker  47 (38.8) 
No record  26(21.5%) 
Treatment
Steroid (systemic & topical)  52 (43%) 
Methotrexate  6 (5%) 
Azathioprine  6 (5%) 
Mycophenolate  3 (2.5%) 
Hydroxychloroquine  4 (3%) 
Infliximab  1 (0.8%) 
Vital status at the end of follow up
Dead  8 (6.6%) 
Transfer to different hospital  1 (0.8%) 
Alive  112 (92.5%) 
a

1 patient-no information about the year of diagnosis.

This cohort mean age is 48 years (SD 2) with female predominance (56%). A total of 14 patients (11.6%) were diagnosed with cancer over the follow up period. 6 patients were diagnosed with cancer before the diagnosis of sarcoidosis (43%). Among them 1 patient later on developed metastatic breast cancer after the diagnosis of sarcoidosis. 1 patient developed 2 different non-melanoma skin cancer lesions before and after the sarcoidosis diagnosis. This patient has been included in both groups. Therefore, total 10 cancer patients after the diagnosis of sarcoidosis have been further evaluated retrospectively using the hospital records. These patients were diagnosed with malignancy either simultaneously or after the diagnosis of sarcoidosis. Among 10 malignancy and sarcoidosis co-existence patients, 7 patients were male and only 3 patients were female, however the total number of female sarcoid patients (56%) were higher in this cohort. Patient with non-Hodgkin's lymphoma, one patient with breast cancer and prostate cancer were diagnosed within one year after the diagnosis of sarcoidosis.

Mean age of patients diagnosed with cancer was 60 years old (SD 15). In Table 2 both groups are described separately.

Table 2.

Distribution of cancer patients by age, sex, number, type of malignancy, and duration of diagnosis.

Type of cancer  Male  Female  Mean age of cancer diagnosis (years)  Mean duration (days) of cancer diagnosis from the diagnosis of sarcoidosis 
Cancer diagnosis after development of sarcoidosis (n=10)
Breast  63  1988 
Prostate  56  231 
Skin (non-melanoma)  55  1131 
Colorectal  72  4322 
Bladder  61  639 
Non-Hodgkin's lymphoma  69  302 
Tonsil  47  534 
Total  60  1224 
Cancer diagnosed before the diagnosis of sarcoidosis (n=6)a
Breast  42  1084 
Lung  75  604 
Non melanoma skin cancer  79  1752 
Malignant Melanoma  58  439 
Total  64  970 
a

1 patient is included in both groups due to relapse of cancer after diagnosis of sarcoidosis.

Our data show an incidence of cancer is 11.6% in our population that increases with age. The profile of cancers identified correlates with the most common malignancies in general population.

Association of malignancy and sarcoidosis is a controversial issue in the literature. The increased incidence of haematological malignancy and cancer of solid organs has been reported in population-based study. Brincker and Wilbek first did a large population-based study in 1973. They studied 2544 pulmonary sarcoidosis patients reported in Danish Institute of Clinical Epidemiology and found the occurrence of malignant lymphoma 11 times and lung cancer 3 times more frequent in sarcoidosis patients.4 However, Romer had revisited the same study group and excluded 14 patients due to diagnostic incorrectness and questioned the validity of the result.9 Romer and colleague did another study on 555 Danish sarcoid patients, where 48 cancer patients were found10. However, this study did not find any increased occurrence of malignancy in sarcoidosis or any association of increase age at diagnosis of sarcoidosis with malignancy.

In our cohort, we noticed one non-Hodgkin's lymphoma but no incidence of lung cancer in patients who develop malignancy after sarcoidosis diagnosis. Though the number of the study group is too small for any conclusive statement. Another Swedish study in 1999 revealed increased relative risk of cancer in sarcoidosis patients including the risk for lung cancer, non-Hodgkin's lymphoma, melanoma, non-melanoma skin cancer, and liver cancer.

Chronic inflammation to the affected organ was proposed to be the putative mediator of high cancer risk.5 We can observe 3 occurrence of non-melanoma skin cancer; although only one patient had skin involvement by sarcoidosis other two patients had no evidence of skin involvement. That one patient with sarcoid skin involvement was diagnosed with skin cancer simultaneously; therefore chronic inflammation could be the causative factor for the development of cancer in this case. Moreover, we found the mean age of sarcoidosis diagnosis in cancer patient was 9 years higher than the sarcoidosis without cancer cohort. A linkage analysis found aetiological relation in one fourth of cases of sarcoidosis and malignancy in whom both conditions co-exist.11 Five of our patients had history of malignancy before the diagnosis of sarcoidosis. It is difficult to denote, whether both condition co-existed or a separate incidence, however all of them later on were diagnosed with sarcoidosis with histology proven evidence from different lymphatic distribution other than the cancerous site with no recurrence of cancer during the follow up time duration. In this group, the mean age of cancer development and sarcoidosis diagnosis were also high, although both patients with breast cancer were diagnosed before 50 years of age.

Incidence of cancer in our sarcoidosis cohort is above 10% with the most common cancers found being those also more common in general population. Age seems to be the main factor for cancer development over time.

We could not draw any association of incidence of specific malignancy with sarcoidosis. Here the sample size is too small for postulating any hypothesis which demands large scale research in this field.

Authors’ contributions

Both authors design the project and identify the patients. First author has done the data collection, literature review, writing the paper and references. Second author has done the literature review, data and paper review and editing of the final draft as well as the clinical follow up of this cohort.

Funding

No funding is received for this study.

Conflict of interest

There is no conflict of interest.

References
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R.P. Baughman, A.S. Teirstein, M.A. Judson, M.D. Rossman, H. Yeager Jr., E.A. Bresnitz, et al.
Clinical characteristics of patients in a case control study of sarcoidosis.
Am J Respir Crit Care Med, 164 (2001), pp. 1885-1889
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Delayed-type hypersensitivity and the immunology of Hodgkin's disease, with a parallel examination of sarcoidosis.
Cancer Res, 26 (1966), pp. 1097-1120
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Sarcoidosis and malignancy.
Clin Dermatol, 25 (2007), pp. 326-333
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The incidence of malignant tumours in patients with respiratory sarcoidosis.
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Risk of malignant neoplasms in patients with pulmonary sarcoidosis.
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The sarcoidosis-lymphoma syndrome.
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