ALCL can be classified into ALK-1 negative and ALK-1 positive ALCL. ALK-1 negative ALCL occurs mainly in older patients (peak incidence ~ 60 y) and in advanced-stage disease. ALK-1 positive ALCL is a clinically aggressive lymphoma that mostly occurs in the first three decades of life [13
]. However, overall survival and longer disease free survival is observed after treatment with aggressive chemotherapy. Patients affected by ALK-1 positive ALCL have a significant better overall survival than ALK-1 negative ALCL patients (5-year overall survival: 70-80% vs. 33-49%) [14
]. It is still controversially discussed if this observation can be explained by the biological role of the ALK-1 fusion proteins or by the younger age of the ALK-1 positive ALCL patients. Unlike ALK-1 positive ALCL, which is characterized by t(2;5)(p23;q35) translocation and resulting in the expression of the NPM-ALK-1 fusion protein, so far no recurrent cytogenetic alterations have been described in ALK-1 negative ALCL.
The presented case illustrates a CD30+, ALK-1+ ALCL of T-cell origin (CD2-/+, CD3+, CD7+, CD8+ and Perforin+) in a pediatric patient. Due to the abundance of small neoplastic cells with pale cytoplasm mixed with some medium-sized and large lymphoid cells this case is best counted among the "small cell variant" of ALCL (10%). Other ALCL subcategories are the common (70-80%) and lymphohistiocytic type (10%).
Primary malignant lymphoma of soft tissue is an infrequent, and often diagnostically challenging neoplasm [16
]. Among those studies which reported the T- or B-cell phenotype of primary soft tissue lymphoma, B-cell accounted for over 90%. Most of those cases showed aggressive histology and were of diffuse large B-cell phenotype [17
]. T cell lymphomas in general and ALCL in particular exceedingly rarely exhibit primary infiltration of skeletal muscle [8
]. Of note, all intramuscular primary ALCL cases reported so far have been ALK-1 positive. Why this T-cell lymphoma could overcome the normally well established protection of skeletal muscle against lymphocytic infiltration is unknown [18
Interestingly, the current ALCL is the first among the reported intra-muscular ALCL primaries to show a CD8 phenotype, which is extremely rare in ALCL. However, trauma, which theoretically could have acted as a stimulatory trigger providing signals for T cell homing to skeletal muscle [18
] was denied by the patient. Moreover, no other infectious or autoimmune process was known from the history or the local findings.
It should also be mentioned in this context that the slightly enlarged lymph nodes were only detected after MRI examination and were not clinically indicative. Unfortunately a lymph node biopsy was not performed. Therefore, a final statement about a possible secondary involvement of the muscle was not possible. However, we consider this possibility less likely because the majority of ALCL patients (70%) presents with advanced stage III to IV disease [3
], which was obviously not the case in our patient.
ALCL has to be distinguished from classical Hodgkin lymphoma (cHL), CD30+ non-Hodgkin B cell lymphomas and very rare ALK-1 positive (and eventually CD30-negative) large B cell lymphomas. Differential diagnosis between ALCL and cHL can be made by expression of cytotoxic molecules such as Granzyme B, Perforin and T-cell-restricted intracellular antigen-1 (TIA1), EMA and CD45/LCA which are typical of ALCL, while positivity for CD15 (in 70% of cases), PAX5 (90%) and LMP1 (in 50%) are typical of cHL. To distinguish ALCL from ALK-1-positive large B cell lymphomas the lack of CD30 expression is critical and the t(2;5) translocation cannot be demonstrated in the B cell lymphoma [19
We conclude that this case represents a very rare manifestation of an ALCL in soft tissue. Despite the anaplastic appearance a favorable outcome was possible after promptly applying aggressive chemotherapy. The expression of the NMP-ALK-1 protein and the young age of the patient might have influenced the positive outcome.