A 29-year-old pregnant woman presented with an abrupt onset of blistering necrotic hemorrhagic lesion on the left hand. It subsequently resolved leaving an eschar. The patient then developed a 1.1-cm demarcated purple nodule located on the dorsal aspect of the right foot (Figure 1). The nodule was tender to palpation. The nodule has since undergone progressive involution. The patient felt otherwise well. A biopsy was performed.
Figure 1. Demarcated purple nodule (1.1 cm) located on the dorsal aspect of the right foot.
The biopsy showed a striking zone of epidermal and dermal necrosis (Figure 2). The viable skin showed a striking angiocentric atypical mononuclear cell infiltrate surrounding and permeating blood vessels with attendant injurious vascular alterations as characterized by endothelial cell necrosis with luminal and mural fibrin deposition (Figure 3). The cells in apposition to the vessels had an immunoblastic appearance. The cells were 12 to 15 µm manifesting moderate amounts of cytoplasm and conspicuous nucleolation. A few other inflammatory cells were noted primarily in the context of neutrophils and eosinophils.
Figure 2. Low power hematoxylin-eosin stain (20×) shows a striking zone of epidermal and dermal necrosis. The viable skin showed a striking angiocentric atypical mononuclear cell infiltrate.
The atypical lymphocytes expressed CD3 (Figure 4), CD8, granzyme, TIA, and CD30 (Figure 5), while the CD20 stain was negative. There was a significant decrement in staining for CD7.
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The patient presented with a striking atypical angiodestructive lymphocytic infiltrate diagnostic of a unique variant of lymphomatoid papulosis, falling under the designation of type E lymphomatoid papulosis. The more common forms of lymphomatoid papulosis fall under types A, B, and C. In type A, large atypical CD30+ T cells are closely apposed to vessels but without striking vasculitic changes and or ensuing significant ischemic alterations. Type B is one which mimics mycosis fungoides exhibiting epidermotropic small cerebriform lymphocytes, while type C lymphomatoid papulosis demonstrates a morphology that draws a close morphologic parallel to anaplastic large cell lymphoma.
The formal recognition of this unique form of angiodestructive lymphomatoid papulosis was by Kempf and colleagues in 2013.1 Interestingly, in 2008, one of our index cases exhibited the classic features of type E angiodestructive lymphomatoid papulosis, where an erroneous diagnosis was initially rendered of an aggressive form of cytotoxic CD8+ T-cell lymphoma.2Among the unique clinical features of type E lymphomatoid papulosis, are the tendency for the cutaneous ulcers to achieve large sizes in excess of 3 cm (the typical size cut off for conventional lymphomatoid papulosis), an overlying eschar, an acral distribution, and the presentation as a unilesional variant of lymphomatoid papulosis. Despite a worrisome appearance, both clinically and histologically the lesions spontaneously regress over a period of 4 to 6 weeks.3
Figure 3 (left). High power hematoxylin-eosin stain (400×) highlights the angiocentric atypical mononuclear cell infiltrate surrounding and permeating blood vessels, with attendant injurious vascular alterations as characterized by endothelial cell necrosis with luminal and mural fibrin deposition.
Figure 4 (middle). A subset of atypical lymphocytes express CD3 immunostaining.
Figure 5 (right). A subset of abnormal angiocentric mononuclear cell infiltrate express CD30 and cytotoxic protein expression.
All cases have angioinvasion and angiodestruction as a cardinal feature. The cells typically have a large immunoblastic appearance. The atypical cells are oftentimes of the CD8 subset, whereby the cytotoxic proteins expressed by the neoplastic CD8 T cells play an integral role in the induction of vascular injury. The abnormal cells express CD30 and cytotoxic protein expression, which is characteristic, whereby the implicated cells express both TIA and granzyme. Observing a reduction in common pan T-cell markers such as CD5 and CD7 is common.
The importance in recognizing this unusual variant of lymphomatoid papulosis is to avoid an erroneous diagnosis of an aggressive angiodestructive T-cell lymphoma, such as an NK/T-cell lymphoma and gamma-delta T-cell lymphoma. Despite certain similarities from a clinical and pathologic perspective, the prognosis and therapeutic approaches are radically different. While angioinvasive lymphomatoid papulosis is indolent and may not require any treatment given the natural clinical course (being one of regression), the aggressive lymphoma mimics have a dismal prognosis and are treated aggressively, even in cases presenting with limited cutaneous disease. Perhaps, the most critical discriminating factor is the clinical course of rapid regression over weeks in the setting of angiodestructive lymphomatoid papulosis. One could also suggest that CD30+ atypical lymphocytes might also support a diagnosis of angiodestructive lymphomatoid papulosis; however, CD30+ is a well-recognized diagnostic pitfall in NK/T-cell lymphoma, whereby a subset of these aggressive lymphomas will exhibit CD30+.4 Conversely, a null phenotype and CD56+, while typical for NK/T-cell lymphomas and a subset of gamma-delta T-cell lymphomas, can also be observed in the setting of indolent CD30+ lymphoproliferative disease.3,5
There is truly no better example than lymphomatoid papulosis where the careful integration of the clinical presentation with the pathologic assessment is key in reaching the most accurate diagnosis.
Dr Magro is the director of dermatopathology at Weill Cornell Medicine in New York, NY. For more information, please visit www.weillcornelldermpath.com.
Dr Solomon is a dermatopathologist and the founder of Tripoint Diagnostics, PLLC in Morrisvillee, NC.
Dr Hedayat is a dermatopatholoy fellow at Memorial Sloan Kettering and Cornell Medical College in New York, NY.
Disclosure: The authors report no relevant financial relationships.
1. Kempf W, Kazakov DV, Schärer L, et al. Angioinvasive lymphomatoid papulosis: a new variant simulating aggressive lymphomas. Am J Surg Pathol. 2013;37(1):1-13.
2. Magro CM, Crowson AN, Morrison C, Merati K, Porcu P, Wright ED. CD8+ lymphomatoid papulosis and its differential diagnosis. Am J Clin Pathol. 2006;125(4):490-501.
3. Magro CM, Crowson AN, Mihm MC. CD30-positive lymphoproliferative disorders including lymphomatoid papulosis, borderline CD30-positive lymphoproliferative disease, anaplastic large cell lymphoma, and T-cell-rich CD30-positive large B cell lymphoma. In: Magro CM, Crowson AN, Mihm MC, eds. The Cutaneous Lymphoid Proliferations: A Comprehensive Textbook of Lymphocytic Infiltrates of the Skin. 2nd ed. Hoboken, NJ: Wiley-Blackwell; 2015:274-309.
4. Schwartz Z, Bowe RB, Coleman M, Magro CM. Pediatric oral Epstein-Barr virus associated self-remitting CD30+ lymphoproliferative disorder: A distinct entity. Ann Diagn Pathol. 2018;37:57-61.
5. Magro CM, Porcu P, Schaefer J, et al. Cutaneous CD4+ CD56+ hematologic malignancies. J Am Acad Dermatol. 2010;63(2):292-308.