Intravascular ALK-negative Anaplastic Large Cell Lymphoma With Localized Cutaneous Involvement and an Indolent Clinical Course

Abstract

Intravascular large T-cell or NK-cell lymphomas rarely present with cutaneous involvement. Intravascular cytotoxic T or NK lymphomas presenting in the skin (cIT/NKL) are often EBV, and reported cases follow a highly aggressive clinical course. Intravascular anaplastic large cell lymphoma (ALCL) by contrast is extraordinarily rare and, when it presents in the skin, raises the question of aggressive clinical behavior in the manner of cIT/NKL versus indolent clinical behavior in the manner of primary cutaneous ALCL. Here we describe a case of localized cutaneous intravascular anaplastic lymphoma kinase-negative ALCL (cIALCL) with a very indolent clinical course. The patient experienced a single cutaneous relapse and remains alive without disease 4 years after diagnosis. Review of the literature reveals multiple clinicopathologic differences between cIALCL and cIT/NKL: distribution (cIALCL, single skin region, P=0.021, Fisher exact test); histology (cIALCL, cohesive with necrosis, P=0.005); immunophenotype (cIALCL, strongly CD30, P=0.021; cIT/NKL, CD56 and/or EBV, P=0.003); and indolent clinical behavior with a trend toward better overall survival (P=0.067, Kaplan-Meier survival analysis). Our index case of cIALCL and 1 other tested case were immunohistochemically confirmed to be intralymphatic (contained within D2-40+vessels) as compared with the blood vessel localization of cIT/NKL. Recognition of cIALCLs as a distinct clinicopathologic entity, and in particular their distinction from aggressive, usually EBV cIT/NKLs, may be possible on the basis of a combination of clinicopathologic criteria, allowing for localized therapy in a subset of patients.

HHV-8-positive and EBV-positive Intravascular Lymphoma

“…The lack of cytotoxic T-cell marker expression and clonal rearrangement of the TCR-gamma gene argues against a diagnosis of NK/T-cell intravascular T-cell lymphoma in this case. There have also been rare reports of intravascular anaplastic large cell lymphomas (ALCL) 24–26 . These lymphomas express CD4 and CD30 but are ALK and EBV-negative and typically form a discrete cutaneous mass with tumor cells localized to the lymphatics.…”

Intralymphatic Cutaneous Anaplastic Large Cell Lymphoma/Lymphomatoid Papulosis

“…D2-40 immunohistochemical analysis was performed as previously described. 6 For CD30 + TLPDs with sufficient available formalin-fixed paraffin-embedded tissue, fluorescence in situ hybridization for rearrangements involving DUSP22-IRF4 locus at 6p25.3 was performed as previously described (Mayo Clinic, Rochester, MN) 21 using a DUSP22 FISH probe produced as described. 26 Statistical analysis was performed using StatPlus:mac, version 2009 (AnalystSoft, Alexandria, VA).…”

“…13,14 An analogous T-cell entity has been described in case series of intravascular cytotoxic, often EBV + NK/ T-cell lymphomas presenting in the skin with an aggressive clinical course. 15,16 The non-ALCL intravascular NK/T-cell lymphomas [15][16][17][18][19][20] involve blood vessels 6 and show highly aggressive clinical behavior. We are left with the question of whether a subset of intravascular T-lymphoproliferative disorders presenting in the skinspecifically those with the morphologic and immunohistochemical findings of ALK À ALCL or other CD30 + TLPDs and without evidence of systemic involvementmay represent part of the spectrum of primary cutaneous ALCL and lymphomatoid papulosis rather than cutaneous manifestation of systemic disease.…”

Intravascular Large B Cell Lymphoma: Widespread but Not Everywhere

“…In fact, it has been demonstrated that most IVLBCL develop and grow within the lumen of blood vessels at a variance with intravascular large cell lymphomas with the T or NK phenotype. The latter have been shown to occur preferentially within lymphatic vessels, which could be differentiated from the hematic ones by virtue of their selective endothelial reactivity for podoplanin [5]. This property of IVLBCL may aid in explaining why the involvement of lymph nodes is not very frequent.…”