ALK+ ALCL is the second most common (25%) subtype of peripheral T-cell lymphoma (PTCL) and accounts for 5% of non-Hodgkin lymphomas (NHLs). It is the most common subtype of PTCL in children and accounts for 10% to 30% of all pediatric lymphomas.^3,4,5 ALK− ALCL represents 40% to 50% of all ALCLs and occurs in the older population, predominantly in the sixth decade of life.² ALK− ALCL is rare in infants, children, and young individuals (<10%).^6,7,8 The median age at diagnosis in pediatric patients is approximately 10.2 to 11.0 years. ALK− ALCL shows a slight male predominance.

Most cases of ALK+ ALCL present with lymphadenopathy. The most common extranodal site is the skin (26%).^9,10,11,12 Other affected sites include bone, lung, liver, and soft tissues.¹ A leukemic presentation is rare and more frequent in the small cell variant.¹³ The bone marrow is affected in a small percentage (10% to 30%) of cases.¹⁴ Affected individuals with ALK− ALCL also present with lymphadenopathy and extranodal involvement.^8,15 Approximately 17% of ALK− ALCL cases have cutaneous involvement.⁸ Most patients have advanced disease (stage III or IV) and B-symptoms.

The cutaneous manifestation of ALK+ ALCL can be precipitated by insect bites.^16,17 Lesions resemble typical arthropod bite reactions without clinical resolution. Most patients with ALK+ ALCL or ALK− have pink papulonodular lesions.^18,19,20 The lesions are more frequently solitary and rarely multiple (Figs. 21-1A,B and 21-2). Rare cases of isolated cutaneous ALCL (C-ALCL), ALK+ have been reported.²¹ Some uncommon clinical appearances include generalized erythroderma,²² orbital lesions,²³ and ichthyosis.²⁴

The prognoses of ALK+ ALCL, ALK− ALCL, and PTCLs not otherwise specified (PTCL-NOS) are significantly different. ALK+ ALCL has a good prognosis with a 5-year survival rate of 70% to 80% in contrast to 49% and 32% 5-year survival rates for ALK− ALCL and PTCL-NOS, respectively.^8,25

A recently described form of ALCL occurring in association with breast implants has a more indolent behavior. Some of these patients can present with skin ulceration.^{26,27,28,29,30} Removal of the implants appears to be curative.²⁹

ALCL is typified by “hallmark” cells: large neoplastic cells with a pleomorphic, horseshoe-shaped nuclei, prominent central Golgi zone, and abundant cytoplasm.³¹ A wreath-like appearance of the nuclei can also be seen. Lymphoma cells are frequently located in perivascular spaces. Several histologic variants are recognized by the WHO classification: (a) lymphohistiocytic (10% to 20%), (b) small cell (5% to 10%),³² (c) Hodgkin-like (3%),³³ and (d) nodular sclerosing variants (<5%). More uncommon variants include multinucleated giant cells and sarcomatoid and myxoid forms.^1,3,4,5 In ALK− ALCL, the cytology of the tumor cells is identical to that of ALK+ ALCL, but the tumor cells tend to be larger and more pleomorphic. Small cell–predominant ALK− ALCL is uncommon and should be classified as PTCL-NOS.⁶

Cutaneous involvement by ALCL is usually manifested by a superficial and deep cutaneous infiltration with extension into the adipose tissue (Figs. 21-3, 21-4, 21-5 and 21-6). The features are similar to primary C-ALCL. Ulceration and acanthosis can occur, whereas epidermotropism is infrequent. Uncommon systemic variants with skin involvement include myxoid³⁴ and small cell forms.^13,32 The small cell variant is frequently associated with widespread disseminated disease, and initial biopsies may be from sites such as skin, liver, or body cavities.⁶ The pyogenic variant (Fig. 21-7) contains numerous histiocytes and acute inflammatory cells, which can potentially mask the tumor. Some of these cases follow an indolent clinical course similar to lymphomatoid papulosis or C-ALCL.^35,36,37 Some cases can also show a predominantly intravascular dissemination pattern, which can potentially mimic an intravascular B-cell lymphoma (Fig. 21-8).