Lymphoblastic lymphoma in two young siblings (coincidence or genetics?): two case reports

Among the homogeneous neoplasms, there are major changes that impact how these cases should be evaluated and diagnosed that have significant therapeutic effects as well as being of biologic interest [1]. Non-Hodgkin lymphoma (NHL) is the fourth most common malignancy in children [2]. It is not considered to be a hereditary disorder, but the occurrence of NHL lymphoma in the same family is called familial NHL [3]. Pediatric NHL shows important differences in the distribution of histologic subtypes to NHL observed in adults who have clinical characteristics represented by almost exclusively diffuse high-grade lymphomas and frequent extranodal involvement [2]. The prognosis for children with non-Hodgkin lymphoma has been improving over the last two decades [4].

Here we present a rare case of pediatric lymphoblastic lymphoma in two sisters, to emphasize the role of precursor genetics in lymphoblastic lymphomas and to suggest a strong relation between these genetics and age at symptom presentation. It is important that research on the genetic basis of pediatric lymphoblastic lymphoma continues, not only to establish its heritability but also to determine its possible impact on treatment and prognosis. We would like to report this case because of its rarity and its contribution to the literature.

It is estimated that 2% of (NHL) cases are familial. This risk of lymphoma occurring in the same family members varies depending on multiple factors, including histopathological type, age at diagnosis, sex, and familial relationship [3]. It is found that male relatives are affected more than females [5]. The incidence of NHL in siblings has been noticed for a long time; it is found that the lifetime cumulative risk of NHL in siblings of a patient with NHL was 1.6%. The lifetime risk was higher when NHL was diagnosed in a sister than in a brother [3]. Most of the common histopathological types of NHL showed familial incidence. Very high familial risk of histological subtypes were found for lymphoplasmacytic, mantle cell, and cutaneous T-cell lymphomas [3]. In the literature review, we found multiple cases of siblings with NHL (some are as case reports and others included in cross-sectional and other research studies). In 2006, Loves et al. reported a family in which three male siblings developed NHL [6]. Those three siblings had different pathological types of lymphoma and were diagnosed at ages 45, 56, and 52 years. Primary gastric NHL, which occurred in two sisters and their father, was also reported by Hayoz et al. in 1993 [7]. The ages of two sisters at diagnosis were 53 and 46 years, and their father’s age was 78 years. Their family had no history of immunodeficiency disorder or cancer. To our knowledge, our case is considered to be the first report of lymphoblastic lymphoma in a pair of siblings in the pediatric population. Some studies found that the diagnosing interval for NHL/NHL sibling pairs is about 1–4 years [8]. In our case, the interval between the appearance of symptoms in the two sisters was very short (less than 1 year). It is estimated that mediastinal non-Hodgkin lymphomas represent about 5% of all non-Hodgkin lymphomas. Mediastinal lymphomas can cause symptoms such as fever, malaise, chest pain, or other symptoms related to compression of adjacent mediastinal structures; however, they might be asymptomatic [9]. Besides the site of tumor, the symptoms and the immune stains were totally similar in the two cases. The occurrence of the disease in the same family leads to many questions about sharable factors that family members could have. These factors may include genetic factors such as tumor formation in Li–Fraumeni syndrome, or immune deficiency disorders, which are very rare. Other important factors are environmental factors such as viral infections like EBV, HIV, or CMV or chemical poisoning and pollution. The two girls have one older sister who is healthy. In our case, the parents are third-degree relatives, and both of the two girls have more than six café au lait spots. This type of spots usually results from recessive hereditary syndromes such as constitutional mismatch repair deficiency syndrome (CMMRD). Although there was no family history of genetic disorders and the girls were previously healthy before NHL diagnosis, the occurrence of the disease at the same time at the same site at this very young age and the presence of the same skin disorders in the two patients may indicate genetic disorders. CMMRD is a syndrome characterized by formation of different types of childhood tumors (hematological, neurological, colorectal, etc.) as well as cutaneous features of neurofibromatosis 1 (NF-1) such as café au lait spots [10]. About one-third of CMMRD patients develop hematological malignancies, and T-cell non-Hodgkin lymphomas, mainly of mediastinal origin, are the most common hematological malignancy [11]. The two patients in our case did not undergo genetic testing because these tests are not available now in our hospital. We suggest that the familial occurrence of the disease might trigger lymphoma formation at a younger age and at unusual sites. However, the prognosis of the disease appears to be the same in familial and nonfamilial cases. The genetic factors are one of the most important factors that affect NHL formation. Although we do not suggest performing scanning of a patient’s siblings when diagnosing NHL, we believe that more research should be done to determine the exact mechanism of how genetics are responsible for lymphoma formation in siblings and how this would affect the diagnosis and treatment of the disease as well as the genetic counseling for affected families.