“I have been accused, perhaps justifiably, of having written more than I have read. I would not presume to speak for the readers of my writings, but I can speak for myself: How enormously instructive and pleasurable it has been! I hope that readers feel the same. A.B.A.” (1)
As with anyone’s passing, life goes on and memories fade. Periodically there is a jolt – a reminder of one’s brilliance and legacy left behind. I never trained directly with Bernie, but had the good fortune to attend his lectures and become acquainted with him personally. There is no dermatopathologist alive who has not been influenced by his teachings, agree with him or not. Based on the quote above, I can assure him posthumously that his writings are still incisive and instructive.
In 1977, prior to the advent of immunohistochemistry, Ackerman and Tanski described “pseudoleukemia cutis” (2). The following is the abstract from article:
Histologic sections from a solitary cystic cutaneous lesion that showed atypical mononuclear cells in the dermis and within blood vessels were diagnosed by several general pathologists and dermatopathologists as leukemia cutis. The patient, who had no other cutaneous lesions, wasconsequently submitted to an extensive investigation for leukemia, which proved negative. Additional and deeper sections from the original block revealed that the cellular infiltrate so suspicious of leukemia cutis was secondary to rupture of a lesion of molluscum contagiosum. The correct histopathologic diagnosis, therefore, was pseudoleukemia cutis. The lessons of the case are that 1) further study of the specimen, solitary as it was and asymptomatic as the patient was, would have obviated worry and the expense and inconvenience of an extensive systemic investigation, and that 2) the diagnosis of leukemia cutis should never be made solely on the basis of histologic sections of skin, but rather after examination of blood and bone marrow.
In the photomicrographs, one can clearly see atypical mononuclear cells within vessels. It is certainly understandable why seasoned pathologists thought this patient had leukemia.
Fast forward four decades to the increasingly reported concept of ILPTCLBs – intralymphatic proliferation of T-cell lymphoid blasts. The most recent report is that of Weingertner et al of a 77-year-old man who was treated with antibiotics for a hip prosthesis infection. Eight weeks later, he developed a rash characteristic of DRESS syndrome, accompanied by fever and eosinophilia. Cutaneous biopsy revealed an atypical T-cell proliferation into the dermal lymphatic vessels. The lymphocytes were mid-sized, with mitoses and apoptotic figures. They were CD3+, CD4+, CD5+ and some were CD30+. There was no T-cell receptor (TcR) clonal rearrangement. Complete regression of cutaneous eruption and eosinophilia was observed after ceasing treatment with antibiotics. The diagnosis was that of a benign atypical intralymphatic T-cell proliferation associated with DRESS. The authors assert that the occurrence of atypical dermal CD30+ T-cells in cutaneous biopsy during benign reactive conditions such as arthropod bites or scabies is well-known. The intralymphatic localization of such atypical reactive lymphocytes, however, is much less common and represents a diagnostic pitfall because it can suggest aggressive intravascular lymphoma (3).
ILPTCBs have also been noted in other inflammatory disorders such as hidradenitis suppurativa (4) and lichen sclerosus (5). The histopathologic criteria for the diagnosis of ILPTCBs are: 1) The presence of an associated inflammatory disorder; 2) clusters of large atypical lymphoid cells confined to D2-40+ lymphatic vessels, although scattered atypical extravascular cells are common; 3) A T-cell phenotype without aberrant features (no loss of pan-T cell markers, no aberrant double positivity/negativity of CD4 and CD8); 4) EBER-1 negativity for the Epstein-Barr virus; and 5) A polyclonal infiltrate as detected by PCR (4).
Intralymphatic histiocytosis (IH) enters the histologic differential diagnosis, and is classically associated with rheumatoid arthritis (3). Immunohistochemistry clearly differentiates IH from ILPTCB; in IH the infiltrate is positive for CD68 and CD163 as opposed to the T-cell profile observed in ILPTCB (4). Of course intravascular lymphoma or leukemia (IVL) must always be ruled out. IVL is an aggressive disease, with most cases representing a diffuse large B-cell lymphoma, although a rare T-cell variant has been reported, including cases with CD30 expression (5). Recently, an indolent form of intralymphatic cutaneous anaplastic large cell lymphoma/lymphomatoid papulosis, with CD30 positivity, has been reported (6).
In conclusion, when intralymphatic atypical lymphocytes are appreciated, it is essential to look at the clinical context, perform immunohistologic stains, and check for clonality, in order to differentiate a benign process from a true lymphoma. As Bernie taught us, clarity in the writing and linguistics of dermatopathology is essential to translate what is seen microscopically to useful clinical information. I am not sure that a report of ILPTCB would mean anything to the referring dermatologist without a detailed explanation. Perhaps we would best utilizing Bernie’s original term, “pseudoleukemia cutis”.
- Weyers W. A. Bernard Ackerman 1936-2008. Am J Dermatopathol 2009; 31: 740-61.
- Ackerman AB, Tanski EV. Pseudoleukemia cutis. Report of a case in association with molluscum contagiosum. Cancer 1977; 40: 813-7.
- Weingertner N, et al. Intralymphatic CD30+ T-cell proliferation during DRESS: A mimic of intravascular lymphoma. J Cutan Pathol 43: 1036-40.
- Calamaro P, Lorenzi L. Intralymphatic proliferation of T-cell lymphoid blasts in the setting of hidradenitis suppurativa. Am J Dermatopathol 2016; 38: 536-40.
- Kempf W, et al. Benign atypical intravascular CD30+ T-cell proliferation: A recently described reactive lymphoproliferative process and simulator of intravascular lymphoma. Am J Clin Pathol 2014; 142: 694-9.
- Samols MA, et al. Intralymphatic cutaneous anaplastic large cell lymphoma/lymphomatoid papulosis: Expanding the spectrum of CD30-positive lymphoproliferative disorders. Am J Surg Pathol 38: 1203-1211.