British Journal of Haematology | 2019
HTLV‐1 status should be recorded in cases of T cell lymphomas/lymphoproliferative disorders – cases of adult T cell leukaemia lymphoma masquerading as other T cell lymphomas/lymphoproliferative disorders could explain some apparent ethnic disparities
Abstract
We read with interest the recent publication by Su et al (2018) on ethnic disparity in primary cutaneous CD30+ T cell lymphoproliferative disorders (PCLPD). Using the National Cancer Database, the authors found that PCLPD patients of African American (AA) ethnicity had poorer overall survival (OS) as compared to patients of Caucasian or Asian ethnicity. Furthermore, the median age at presentation was lower among AA patients. The survival disadvantage of AA patients persisted after adjusting for patient and disease characteristics, socioeconomic factors and treatments received. Su et al (2018) state that certain factors could have impacted on their analysis – (i) the cohort might have included patients with secondary cutaneous involvement by systemic CD30+ T cell lymphomas; (ii) lack of central pathological review could account for other forms of cutaneous T cell lymphomas being misclassified as PCLPD; and (iii) lack of data on the specific subtypes of PCLPD (primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis and borderline cases) could also have impacted on apparent differences in survival. We believe that the most critical factor not considered in the study was the Human T-lymphotropic virus type 1 (HTLV-1) status of the patients, which might have been available in their database. HTLV-1 has been aetiologically linked to adult T-cell leukaemia/lymphoma (ATLL). HTLV-1 infection is endemic in sub-Saharan Africa, the Caribbean and parts of South America, and southern Japan (Chang et al, 2014). Transmission routes for HTLV-1 include vertical transmission from mother to child through breast-feeding, sexual contact, blood transfusions and needle sharing among injection drug users (Pezeshkpoor et al, 2008; Iwanaga et al, 2012; Chang et al, 2014). Most of the available studies on HTLV-1 prevalence in the USA relate to blood donors, pregnant women or hospitalised patient cohorts. Among them, AAs are significantly more likely to be HTLV-1 positive as compared to other racial groups (Gessain & Cassar, 2012). Chang et al (2014) reported a prevalence of HTLV-1 positivity among AA, White and Hispanic blood donors of 32 9, 1 71 and 2 32 per 100 000, respectively. Furthermore, data from the North American Association of Central Cancer Registries has documented a higher incidence of ATLL among AA patients (Yamamoto & Goodman, 2008). Additional case series of ATLL cases from the USA have also documented this, particularly among south-eastern states, such as Florida (Harrington et al, 1995; Gessain & Cassar, 2012). ATLL is an aggressive lymphoma that occurs in 2–5% of HTLV-1 infected persons, and manifests clinically after several decades of acquiring the infection. The incubation period from infection with HTLV-I to the development of ATLL has been estimated to be 15–20 years or more. ATLL can present in acute, chronic, lymphomatous and smouldering forms. Median OS of the acute, lymphomatous and chronic types are reported to be 6 2, 10 2 and 24 3 months, respectively (Tokura et al, 2014). Skin involvement is a salient feature of ATLL and is seen in up to two-thirds of patients (Tokura et al, 2014). Clinical presentations in skin could include papules, plaques, nodules, tumours, erythematous nonspecific patches, and erythroderma (Pezeshkpoor et al, 2008). Morphological manifestations of the cutaneous presentation of ATLL are highly variable. Neoplastic cells can be pleomorphic small, medium or large cell type, or anaplastic; rarely the overall picture can resemble angioimmunoblastic T cell lymphoma. Similar to CD30+ PCLPD, ATLL cells are CD4+ ab T cells and a proportion of cells may express CD30 (Swerdlow et al, 2017). On these grounds, some cases of skin ATLL may resemble CD30+ PCLPD and be wrongly classified as such. ATLL may also show epidermal infiltration with Pautrier-like microabscesses, thereby mimicking mycosis fungoides (MF). On cytological grounds, the irregular nuclear contours of ATLL cells can cause confusion with cerebriform nuclei seen in neoplastic cells of MF or Sezary syndrome (SS). Furthermore, similar to MF/SS, ATLL cells are also CD4+ ab T cells. Although CD25 expression is characteristic of ATLL, a proportion of neoplastic cells in other T cell lymphomas can express CD25. In addition, CD25 expression may not be evaluated if ATLL is not suspected. Hence, awareness of the HTLV-1 status of the patient would be crucial for precise lymphoma classification in these cases. We also take note of previous studies that suggested worse prognosis for AA patients with MF as compared to MF patients of Caucasian ethnicity (Su et al, 2018). We suspect that this is again a reflection of ATLL being misclassified as MF in AA patients. correspondence