Incidence trends of primary cutaneous B‐ and T‐cell lymphoma before and after the COVID‐19 pandemic

Dear Editors,

Primary cutaneous lymphomas (PCLs) are a diverse group of T‐ and B‐cell lymphomas that present in the skin without evidence of extracutaneous disease at the time of diagnosis. They are classified by cell origin into primary cutaneous T‐cell lymphomas (PCTCLs) and primary cutaneous B‐cell lymphomas (PCBCLs). ¹ The complex pathophysiology of the development of PCLs is thought to involve chronic antigen stimulation from unknown exposures, potentially ranging from chemicals to microbial agents. ²

The Coronavirus disease 2019 (COVID‐19) pandemic has affected the epidemiological landscape of numerous human diseases, including autoimmune diseases, infections, and malignancies. This shift may be directly or indirectly associated with the infectious agent and its immunoregulatory properties, the massive vaccination against SARS‐CoV‐2 and the associated activation of immunity, or with changes in health behaviors among patients. ^{3 –‐ 5} However, little is known about the potential impact of the pandemic on the epidemiology of PCLs. The aim of this study was to present epidemiological insights arising from a large PCL database and examine the possible impact of COVID‐19 disease in the incidence PCLs.

We conducted a retrospective review of all PCL diagnoses at a single hemopathology referral center specializing in cutaneous lymphomas in Attica, Greece, over a 15‐year period (2009–2023). Crude annual incidence rates (IRs) per 100,000 individuals were estimated overall and stratified by sex and age group. Incidence rates were estimated based on the population of permanent residents in the Attica region on January 1 of each corresponding year, as reported in the Eurostat Database. ⁶ Statistical analyses were performed using Stata SE, version 13.0 (StataCorp) and annual percentage changes (APCs) were estimated using the US National Cancer Institute Joinpoint Regression Program (version 5.1.0.0). The joinpoint year was defined as the year in which statistically significant trend changes had occurred.

In total, 1,355 patients (818 males) were diagnosed with PCL between 2009 and 2023 including 1,098 PCTCLs and 257 PCBCLs. Table 1 and online supplementary Table S1 present the crude and age‐adjusted annual incidence rates per 100,000 individuals along with the absolute numbers of cases for each category. In the 2009–2011 period, the crude IR of PCTCLs per 100,000 was 1.0, while in the 2022–2023 period (COVID‐19 pandemic/post‐pandemic era) it was 2.4. The highest IR observed for PCTCLs was 3.1 during the 2018–2019 period. From 2009 to 2018, the crude IR for PCTCLs rose significantly, averaging a 14% increase per year, followed by a decrease from 2018 to 2023 (APC: –4.8; 95% confidence interval [CI]: –39.2 to 5.2) (Figure 1). In contrast, PCBCLs exhibited a steady increase in IRs over the entire study period.

TABLE 1.

Crude and age‐adjusted annual incidence rates (per 100,000 individuals) of primary cutaneous T‐cell lymphoma and primary cutaneous B‐cell lymphoma in Athens and the greater Attica area in Greece from 2009 to 2023, overall and per specific time periods. Age and sex‐specific incidence rates are presented per period. Absolute numbers for each diagnosis per age group, sex and specific time periods are also presented.

PCTCL	2009‐2023	2009‐2011	2012‐2014	2015‐2017	2018‐2019	2020‐2021	2022‐2023
Total number	1098	121	163	242	234	156	182
Overall incidence
Crude	1.9	1.0	1.4	2.1	3.1	2.1	2.4
Age‐adjusted	1.3	0.7	0.9	1.5	2.1	1.5	1.6
Subject age at diagnosis (years) (absolute numbers)
0–49	268	29	34	64	54	39	49
50–59	215	21	22	60	42	35	35
60–69	264	26	39	53	62	41	43
70–79	216	28	43	36	48	28	35
≥80	132	17	25	29	28	13	20
Subject age at diagnosis (years) (incidence rates)
0–49	0.8	0.4	0.5	0.9	1.2	0.9	1.1
50–59	2.7	1.4	1.4	3.8	4.0	3.3	3.0
60–69	4.0	2.2	3.0	4.0	7.1	4.6	4.6
70–79	4.4	2.9	5.0	3.8	7.4	4.2	4.7
≥80	3.8	3.2	4.1	4.3	6.0	2.7	2.7
Sex (absolute numbers)
Male	698	79	96	154	150	100	119
Female	400	42	67	88	84	56	63
Sex (incidence rates)
Male	2.6	1.4	1.7	2.9	4.2	2.8	3.3
Female	1.3	0.7	1.1	1.5	2.1	1.3	1.6
Diagnosis (absolute numbers)
Mycosis fungoides (MF)	935	96	141	201	202	133	162
All other PCTCL except for MF	163	25	22	41	32	23	20
Lymphomatoid papulosis	67	20	12	6	9	12	8
Diagnosis (incidence rates)
Mycosis fungoides (MF)	1.6	0.8	1.2	1.8	2.7	1.8	2.1
All other PCTCL except for MF	0.3	0.2	0.2	0.4	0.4	0.3	0.3
Lymphomatoid papulosis	0.1	0.2	0.1	0.1	0.1	0.2	0.1
PCBCL
Total number	257	18	22	55	44	55	63
Overall incidence
Crude	0.4	0.2	0.2	0.5	0.6	0.8	0.8
Age‐adjusted	0.3	0.1	0.2	0.3	0.4	0.6	0.5
Subject age at diagnosis (years) (absolute numbers)
0–49	63	7	6	11	8	20	11
50–59	54	4	7	11	8	10	14
60–69	57	4	4	12	11	11	15
70–79	51	2	3	10	12	11	13
≥80	32	1	2	11	5	3	10
Subject age at diagnosis (years) (incidence rates)
0–49	0.2	0.1	0.1	0.2	0.2	0.5	0.2
50–59	0.7	0.3	0.5	0.7	0.8	0.9	1.2
60–69	0.9	0.3	0.3	0.9	1.3	1.2	1.6
70–79	1.0	0.2	0.3	1.1	1.8	1.6	1.9
≥80	0.9	0.2	0.3	1.6	1.1	0.6	1.4
Sex (absolute numbers)
Male	120	9	9	27	20	27	28
Female	137	9	13	28	24	28	35
Sex (incidence rates)
Male	0.4	0.2	0.2	0.5	0.6	0.8	0.8
Female	0.5	0.1	0.2	0.5	0.6	0.7	0.9

FIGURE 1.

Annual percent changes (a) in primary cutaneous T‐cell lymphoma and (b) primary cutaneous B‐cell lymphoma incidence rates in Athens and the greater Attica area in Greece, overall, derived from trend analysis performed using the Joinpoint Regression Program (version 5.1.0.0) provided by the NCI.

According to our findings, the incidence of PCTCLs in Greece seems to have stabilized after hitting a peak incidence in 2018 along with a steady state increase in PCBCL diagnoses throughout the study period. Our data indicate that the COVID‐19 pandemic did not impact the diagnosis rates of skin lymphomas in Greece, as the plateau observed after 2018 has continued steadily over the past 2 years, even after hospitals resumed pre‐pandemic operations. In contrast, an increase in type B lymphomas was observed during the 2020–2021 pandemic period and continued in the years that followed. The tumorous morphology of PCBCLs appears to have prompted patients to seek medical attention even during the pandemic. Although the number of cases is limited, a doubling in CD30⁺ lymphoma diagnoses was noted. Globally, CD30⁺ lymphomas have been reported with possible associations to COVID‐19 infection or vaccination, but current data are insufficient to draw definitive conclusions. ⁷

An increase in PCTCL cases among individuals aged ≥ 60 was observed during the 2018–2019 period; however, this trend did not persist in subsequent years. A potential explanation for this decline could be that elderly patients may have reduced their medical visits following the emergence of COVID‐19, particularly for skin disorders that are not typically classified as medical emergencies. This could have left a significant number of patients with mild disease undiagnosed. Nonetheless, there are no official data specifically addressing this issue, whereas the observed trend of increased incidence rates in elderly patients during 2018–2019, as expressed by annual percent change, was not found to be statistically significant based on Joinpoint regression analysis.

The exact etiologies behind those epidemiological trends remain unknown, and further studies are warranted to shed more light into this phenomenon. Moreover, more relevant epidemiological data from around the globe are needed in order to depict more diverse populations.

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Supporting information

Supplementary information