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The alphabetization of lymphomatoid papulosis: Focus on “F”

DII small banner By Warren R. Heymann, MD
April 3, 2017

Follicular Lymphomatoid Papulosis
Follicular lymphomatoid papulosis. Recurrent papulonodular lesions on face (A to C). Patient had similar lesions on extremities.
Credit: JAAD

Seven years ago, today (April 3rd, 2010) my wife purchased an iPad on its inaugural release date. The only choices to be made were how much storage was desired or if there should also be 3G connectivity. Today you can choose either an iPad mini, iPad, or iPad Pro (two sizes), combined with different storage and connectivity options. For example, if you want to be specific, you can say that you purchased an iPad Pro, 9.7 inch, 128 GB, cellular and Wi-Fi. The fact remains that you still bought an iPad, which basically has all the same implications and functions of every other iPad.

The 50th anniversary of Warren Macaulay’s seminal description of lymphomatoid papulosis (LyP) is approaching. The abstract of this landmark article (1) follows:

A 41-year-old woman has an asymptomatic eruption of three years’ duration. The clinical course is benign and is characterized by a continuing, random, coming and going of papules, some of which undergo necrosis, and all of which involute spontaneously within three to four weeks. Results of repeated physical examinations and laboratory studies are normal. Yet, biopsies of the skin lesions show an alarming infiltrate of anaplastic cells of disputatious origin, suggesting to most reviewers a diagnosis of malignant lymphoma. A number of comparable cases are reviewed, their similarity implying an uncommon entity.

LyP is considered within the spectrum of CD30+ lymphoprolferative skin disorders. CD30, previously known as Ki-1 antigen, is a 120-kDa type I transmembrane glycoprotein of the tumor necrosis factor receptor superfamily, acting as a cell surface cytokine receptor on activated T and B cells. The etiology of Lyp is unknown, although it is presumed to be a reactive disorder resulting in the CD30 overexpression. The risk of secondary malignancies in LyP can occur between 5% to 30% of patients, with the majority being mycosis fungoides, anaplastic large cell lymphoma (ALCL), or Hodgkin disease. There are currently 5 accepted histologic subtypes of LyP (A – with large Reed-Sternberg-like cells; B – resembling mycosis fungoides; C – appearing as ALCL; D – CD8+; E – angiocentric/angiodestructive), and a proposed sixth type F (follicular), which will be discussed in greater detail. Although patients with LyP often undergo treatment (with first-line therapies including topical corticosteroids, phototherapy, or methotrexate), to date, therapy has not been reported to alter the natural history of LyP or the risk of secondary malignancy (2).

Follicular LyP (FLyP, type F) is a rare, variant of LyP. Kempf et al noted follicular involvement in 11 patients derived from 113 cased of LyP. Six cases were classified as type C and 4 as type A, whereas the remaining case manifested epidermotropism of small lymphocytes in a background of a typical type A lesion (overlapping type A/B). Perifollicular infiltrates of CD30(+) atypical lymphoid cells were seen in all 11 cases, with infiltration of the follicular epithelium in 8 cases. Hyperplasia of the follicular epithelium was observed in 4 cases; ruptured hair follicles, in 3 cases; and follicular mucinosis, in 2 cases. In addition to hair follicle infiltration, atypical cells were recognized within sebaceous glands in 2 lesions. New findings were presence of numerous intrafollicular neutrophils in 2 patients, who clinically had pustules in addition to papules. Other histopathological features encountered included perieccrine infiltration (n = 5), focal subcutaneous involvement (n = 4), granulomatous inflammation (n = 3), epidermal hyperplasia (n = 2), and 1 each of infiltration of muscle bundles, numerous eosinophils in the infiltrate, and angiocentricity (3).

Dore et al described 3 cases of typical LyP demonstrating folliculotropism and follicular mucinosis histopathologically. The authors suggest that LyP should be considered alongside MF in the differential diagnosis of follicular mucinosis with accompanying atypical lymphocytic infiltration (4). Ross et al emphasize that FLyP may masquerade as more common folliculocentric diseases including eosinophil-rich folliculitis, bacterial or parasitic infections, follicular MF, eosinophilic dermatosis of hematologic malignancy, and insect bite or hypersensitivity reactions, among others (5). It is quite possible that this mimicry means that FLyP is an underreported (or misdiagnosed) entity.

Regarding the alphabetization of LyP, I imagine the alphabet continuing with types G (granulomatous), H (hyperplastic), I (indeterminate), etc. While appealing on one level, does it really matter? There may be histologic overlap in any given patient between different variants. If the therapeutic approach, need to follow patients for secondary malignancies, and ultimate prognosis is uniform for the different subtypes, should we continue to subcategorize LyP patients? Kempf et al believe that the alphabetic approach to categorizing LyP is complex, and not clinically helpful. They propose classifying LyP based on histology, immunologic phenotype, genotype (if available) and clinical presentation. For example, instead of a patient with type A LyP, they could be described as mixed cellular, CD4+ and CD30+, with acral, pustular lesions.
I believe that Kempf et al are correct. It is time for a revitalized reclassification of LyP. By taking their approach (or another similar modification), the likelihood of discerning differences in the subgroups will increase, helping to guide therapy and management of this enigmatic disease.

1. Macaulay WL Lymphomatoid papulosis: A continuing self-healing eruption, clinically benign – histologically malignant. Arch Dermatol 1968; 97: 23-30.
2. Sauder MB, et al. CD+ lymphoproliferative disorders of the skin. Hematol Oncol Clin N Am 2017; 317-334.
3. Kempf W, et al. Follicular lymphomatoid papulosis revisited: A study of 11 cases, with new histopathological findings. J Am Acad Dermatol 2013; 68: 809-16.
4. Dore E, et al. Follicular lymphomatoid papulosis with follicular mucinosis: A clinicopathologic study of 3 cases with literature review and conceptual reappraisal. J Cutan Pathol 2017; 44 360-6.
5. Ross NA, et al. Follicular lymphomatoid papulosis: An eosinophilic-rich follicular subtype masquerading as folliculitis clinically and histologically. Am J Dermatopathol 2016; 38: e1-10.
6. Kempf W, et al. Lymphomatoid papulosis – making sense of the alphabet soup: A proposal to simplify terminology. J Dtsch Dermatol Ges 2017 Mar 2 [Epub ahead of print.

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