Mycosis Fungoides

In my experience, as well as in that of others, this is the most common cutaneous lymphoma in children and adolescents (about one-third of cases) [1, 3–9]. The low incidence (10%) reported by Boccara et al. [2] may be explained by selection bias, as cases were observed at a children’s hospital located in a large city with many other dermatological facilities that may have managed other cases of mycosis fungoides in the pediatric population. In addition, aggressive cases (e.g., acute leukemia) are overrepresented in the study by Boccara et al. [2], providing a further explanation for the low percentage of cases of mycosis fungoides.

Children and adolescents may present with conventional lesions of mycosis fungoides identical to those observed in adults, but in young age the disease frequently shows hypopigmentation clinically and the presence of a cytotoxic infiltrate histopathologically [10–14]. Another peculiar type of mycosis fungoides in young patients simulates pityriasis lichenoides et varioliformis acuta (PLEVA) and/or pityriasis lichenoides chronica clinically and histopathologically [15–19]. Some authors pointed at a possible relationship between the two disorders [2], and cases of “transformation” of pityriasis lichenoides chronica into mycosis fungoides have been reported [20]. However, I have observed many cases of otherwise conventional mycosis fungoides showing histopathologically features that were indistinguishable from those of pityriasis lichenoides, and it may be that cases with “transformation” represented in truth mycosis fungoides from the outset (see also Chapter 26, the section on pityriasis lichenoides et varioliformis acuta, and Chapter 2, the section on PLEVA-like mycosis fungoides).

Besides the two variants of mycosis fungoides discussed above, follicular mucinosis has been observed commonly in children, adolescents, and even neonates [21–23]. Many of these cases represent the so-called “benign” type of follicular mucinosis, but association with mycosis fungoides has been reported in the pediatric population [21, 24, 25]. Localized pagetoid reticulosis (Woringer–Kolopp) is another rare variant of mycosis fungoides that is probably more frequent in children and adolescents than in adults [26]. Indeed, the first description by Woringer and Kolopp concerned a 13-year-old boy.

It is important to underline that in children and adolescents the clinicopathologic differential diagnosis of mycosis fungoides is not identical to that of adult patients. Some types of pseudolymphoma are mostly restricted to young individuals (e.g., annular lichenoid dermatitis of youth), and others arise only in adults (e.g., lichenoid keratosis). I have never seen cases of pseudolymphomatous atopic dermatitis in pediatric patients, even if the disease is common in this age group. Although infection by Borrelia species occurs often in children and adolescents, and Borrelia-induced lymphocytoma is common in young patients, acrodermatitis chronica atrophicans is exceptional in the pediatric population.

The prognosis of mycosis fungoides in children and adolescents seems to be similar to that of adult patients [1, 12, 27, 28], and only one report pointed at a more aggressive course [29]. On the other hand, early onset of the disease allows time for progression during the lifetime of patients.

Sézary Syndrome

Only one case of Sézary syndrome in an 11-year-old girl has been reported [30], showing that the disease is exceedingly rare in young patients and should not be considered as a serious differential diagnosis when evaluating erythroderma in children and adolescents. In this context, erythroderma in neonates evokes a spectrum of differential diagnoses among which Sézary syndrome has no place at all.

Lymphomatoid Papulosis

In my experience, this is the second most common cutaneous lymphoma in children and adolescents, but it was the most frequent in the study by Boccara et al. [2]. There are no specific clinicopathologic features of lymphomatoid papulosis in young patients that warrant discussion over what has already been written in Chapter 4. Progression into a second lymphoma has not been reported in one study on young patients [31], but I have observed children with lymphomatoid papulosis and a second nodal lymphoma (Hodgkin lymphoma or anaplastic large cell lymphoma), and other cases are reported as well [32].

Cutaneous Anaplastic Large Cell Lymphoma

Children and adolescents may be affected by both primary and secondary cutaneous anaplastic large cell lymphoma. As well as in adult cases, staging investigations should always be carried out in young patients, too.

In contrast to primary cutaneous anaplastic large cell lymphoma arising in adults, several cases occurring in pediatric patients are positive for ALK-1 and show the t(2;5)(q23;q35) translocation, suggesting that ALK-1⁺ cutaneous anaplastic large cell lymphoma is not infrequent in young individuals [33, 34]. The prognosis seems to be similar to that of conventional cutaneous anaplastic large cell lymphoma.

Subcutaneous Panniculitis-like T-cell Lymphoma

This type of lymphoma has been described in young patients, but is rare in this age group [2, 35–37]. The clinicopathologic features are similar to those observed in adults. A hemophagocytic syndrome has been observed in pediatric cases with an aggressive course [38].

The differential diagnoses of subcutaneous panniculitis-like T-cell lymphoma in children are in part different from those considered for adult patients. In fact, although lupus erythematosus panniculitis can be observed in childhood, it is rare in this age group [39]. On the other hand, in young children with immune deficiency disorders a lobular panniculitis indistinguishable from that of subcutaneous panniculitis-like T-cell lymphoma may be observed, even with clonality of the T lymphocytes, representing an important differential diagnosis. Histopathologic features similar to those observed in subcutaneous panniculitis-like T-cell lymphoma have also been described in a macrophage activating syndrome presenting in pediatric patients [40] and in lipoatrophic panniculitis of the ankles in childhood [41]. For practical purposes, a diagnosis of subcutaneous panniculitis-like T-cell lymphoma in young children should be accepted only if other causes of lobular panniculitis have been excluded.

Primary Cutaneous Aggressive Epidermotropic CD8⁺ Cytotoxic T-cell Lymphoma

Cutaneous aggressive epidermotropic CD8⁺ cytotoxic T-cell lymphoma is exceptional in pediatric patients, but one convincing case has been reported in a 6-year-old child [42]. Differentiation from CD8⁺ mycosis fungoides (a common phenotype in children and adolescents) and from lymphomatoid papulosis, type D, may be very difficult, and only follow-up data may be diriment. As a general rule, a diagnosis of primary cutaneous aggressive epidermotropic CD8⁺ cytotoxic T-cell lymphoma in children and adolescents should be made only if mycosis fungoides and lymphomatoid papulosis can be ruled out by compelling clinicopathologic evidence.

Primary Cutaneous γ/δ T-cell Lymphoma

This lymphoma is rare in the pediatric population, but sporadic cases are reported [2]. There are no relevant clinicopathologic differences from adult cases. Differentiation from mycosis fungoides with γ/δ phenotype is crucial, as prognosis and management are completely different.

Extranodal NK/T-cell Lymphoma, Nasal Type

Only a few cases of pediatric cutaneous extranodal natural killer (NK)/T-cell lymphoma, nasal type, have been reported [2]. I have seen rare cases arising in adolescents who eventually succumbed to their disease. The clinicopathologic features are similar to those observed in adults.

Primary Cutaneous Peripheral T-cell Lymphoma, Not Otherwise Specified (NOS)

There are reports on children and adolescents with cutaneous peripheral T-cell lymphoma, not otherwise specified (NOS), but it is unclear whether patients presented with primary cutaneous manifestations or with secondary skin involvement of a nodal lymphoma [43]. Primary cutaneous cases are probably exceptional, if they exist at all.

Cutaneous CD4⁺ Small/Medium T-cell Lymphoma

In my experience, cutaneous CD4⁺ small/medium T-cell lymphoma represents the third most common entity of cutaneous lymphomas in children and adolescents. Several cases have been reported [1, 44]. The clinicopathologic features are similar to those observed in adults, and prognosis of solitary lesions located on the head and neck region is excellent.

Cutaneous Angioimmunoblastic T-cell Lymphoma

This type of lymphoma is exceedingly rare in children and adolescents, and only anecdotal cases have been reported [45]. The involvement of the skin represents a secondary manifestation of an extracutaneous (nodal) lymphoma. Care should be taken to distinguish true angioimmunoblastic T-cell lymphomas from the more common cases of cutaneous CD4⁺ small/medium T-cell lymphoma presenting with phenotypic features of follicular helper T-lymphocytes (T_FH).

Hydroa Vacciniforme-like Lymphoma

This cutaneous lymphoma arises exclusively in children and adolescents. Although primarily reported in Latin American countries [46–49], several cases have been recently observed in Asiatic countries as well [50, 51]. Onset in Caucasians is exceptional. A detailed description is provided in Chapter 10.

Adult T-cell Lymphoma/Leukemia

Most patients with adult T-cell lymphoma/leukemia (ATLL) are adults and the elderly, but the disease has been observed rarely in adolescents [52]. Clinicopathologic features are indistinguishable from those of mycosis fungoides, thus demonstration of infection with human T-cell lymphotropic virus I (HTLV-I) is mandatory in order to confirm the diagnosis.

Cutaneous Follicle Center Lymphoma

Cutaneous follicle center lymphoma is very rare in children and adolescents, and only a few cases have been reported [53]. One patient presented with the spindle cell variant of the disease [54]. With the exception of the clinical picture of Crosti’s lymphoma, which is not found in pediatric patients, clinicopathologic features are similar irrespective of the age of onset.

Cutaneous Marginal Zone Lymphoma (Cutaneous MALT Lymphoma)

This is a relatively frequent cutaneous lymphoma in children and adolescents, and several patients have been observed [1, 55, 56]. Cases reported as primary cutaneous plasmacytoma probably represented examples of the plasmacytic variant of cutaneous marginal zone lymphoma [56]. The clinicopathologic features are similar to those observed in adults and the prognosis is excellent.

In a study on marginal zone lymphomas from different organs in young patients, several cases were located within the lymph nodes or the conjunctiva, but only one within the skin [57], suggesting that in the pediatric population cutaneous cases are less frequent than extracutaneous ones.

Cutaneous Burkitt Lymphoma

Although many cases of extracutaneous Burkitt lymphoma arise in pediatric patients, most reports on cutaneous involvement concern adults, and only a few children with cutaneous Burkitt lymphoma have been observed [58]. It is unclear whether the low incidence is due to underreporting or if it represents a true phenomenon in young individuals. Clinicopathologic features are similar, irrespective of age.

Cutaneous Intravascular Large Cell Lymphoma

Both the more frequent B-cell and the exceedingly rare NK/T-cell type of intravascular large cell lymphoma arise almost exclusively in adults or elderly patients. One congenital case of intravascular NK/T-cell lymphoma was detected at autopsy [59]; in spite of involvement of multiple organs, tumor complexes were not present in the skin in this case.

Cutaneous Lymphomatoid Granulomatosis

Lymphomatoid granulomatosis is a lymphoproliferative disorder observed more often in adults, but children may be affected, particularly immunosuppressed ones [60]. The clinicopathologic features are similar to those observed in adults.

Cutaneous Lymphomas in Immune Suppressed Children and Adolescents

A few cases of cutaneous lymphoma associated with Epstein–Barr virus (EBV) infection have been reported in children with immune suppression due to different causes (congenital immune deficiencies, post-transplantation setting, HIV infection) [2, 61]. The clinicopathologic features are similar to those described in immunocompromised adults.

Cutaneous Manifestations of Myelogenous Leukemia

Most cases of myeloid leukemia in children are congenital (5/6 in the study by Boccara et al.) and of monoblastic type [2]. The clinical presentation is that of so-called “blueberry muffin” neonates (see Chapter 20). Although isolated cases with spontaneous remission have been observed, the disease usually runs an aggressive course.

Blastic Plasmacytoid Dendritic Cell Neoplasm

Cutaneous cases arising in children and adolescents are well documented [1, 62]. The clinicopathologic and prognostic features are similar to those observed in adults.

Cutaneous Lymphoblastic Lymphoma (B- or T-cell)

Cases of B-lymphoblastic lymphoma with primary cutaneous presentation are well documented in children and adolescents [1, 2, 63]. Considering primary and secondary cases together, cutaneous lymphoblastic lymphoma is not uncommon in pediatric patients and represents an important differential diagnosis of rapidly growing tumors, particularly on the head and neck area.