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Something from nothing: The role of random skin biopsies

DII small banner By Warren R. Heymann, MD
Sept. 22, 2017

random biopsy
There are a few reports suggesting the usefulness of the random or blind skin biopsy from normal-appearing skin for diagnosis of intravascular lymphoma. Punch biopsy results from the abdomen. A, Intravascular large lymphoid cells. B, CD20+ tumor cells. (A, Hematoxylin-eosin stain; B, immunohistochemical stain.)
Credit: JAAD
As dermatologists we hone our skills on visual diagnostic clues, allowing us to choose optimal lesions to biopsy for clinical-pathologic correlation. The concept of random skin biopsies (RSB) of normal skin searching for pathology may seem foreign (or heretical); however, in the right circumstances, it may yield vital diagnostic information.

Pujol et al described a 76-year-old woman who had persistent generalized pruritus without cutaneous lesions throughout her entire course. Skin biopsy specimens obtained from normal-looking pruritic skin revealed Pautrier’s microabscesses with a monoclonal T-cell rearrangement diagnostic of cutaneous T-cell lymphoma. (1)
Biopsies of “normal” flexural skin may show histologic features of pseudoxanthoma elasticum in patients who present to ophthalmologists with angioid streaks. (2) Biopsies of the abdominal fat pad, usually by fine needle aspiration, but possibly with better results using telescoping fat pad biopsies, may be utilized in evaluating patients with suspected systemic amyloidosis. (3)

Increasingly, RSB have been reported to be valuable for patients with “B” type symptoms, including fever of unknown origin (FUO), when lymphoma is suspected.

Gill et al were the first to report the use of RSB to diagnose intravascular lymphoma (IVL) in a 60-year-old man who was admitted for FUO, night sweats, weight loss, and lethargy. (4) A series of 24 of suspected lymphoma patients were consulted for RSB – none had cutaneous lesions suspicious for lymphoma. The RSB were incisional, including subcutaneous tissue; 3 cases (13%) were diagnosed with intravascular lymphoma. Two cases (8%) were diagnosed with cytophagic histiocytic panniculitis from normal-appearing skin; subsequent investigation led to the diagnosis of T-cell lymphoma. (5)

Most recently, a study of 32 patients with FUO without skin lesions underwent RSB for diagnosis of IVL was published. Clinical data, including fever, neurological symptoms, hematologic disorders, organomegaly, bone marrow (BM) study, hypoxemia and serum level of lactate dehydrogenase (LDH), was evaluated. Seven of the 32 patients were definitively diagnosed with IVL. In addition to FUO, 2 IVL patients also suffered from dyspnea and neurological disorders. Patients who had FUO accompanied by hematologic disorders, high LDH, a negative bone marrow (BM) study and no lymphadenopathy or hepatosplenomegaly had a statistically significant tendency to have IVL diagnosed by RSB (P = .03). FUO with hypoxemia was also identified as a statistically significant indication for RSB (P = .02). The authors concluded that RSB is a reliable method for diagnosis of IVL, especially in patients with FUO and any 1 or more of the 4 following abnormalities: (1) hematologic abnormalities; (2) high serum LDH; (3) hypoxemia; and/or, (4) unusual neurological symptoms with co-existing hematologic abnormalities and without lymphadenopathy, hepatosplenomegaly or BM abnormality. (6)

Unquestionably, if cutaneous lesions are present in suspect cases of IVL, those lesions should be biopsied. Arai et al examined 3 cases of IVL, comparing the occurrence of tumor cells in lesional and healthy-looking skin by performing RSB of 32 separate sites. The authors found that 16 of the 17 sites on lesional skin and only 1 of the 15 sites on the healthy-looking skin were positive for neoplastic cells. (7) This finding confirmed that IVL cells occur more frequently in the lesional skin than in the healthy-looking skin. RSB should be utilized when no obvious lesions are present.

In conclusion, the next time you get a request from a colleague requesting a RSB, or from a pruritic patient whose cause of pruritus is an enigma, don’t roll your eyes — consider performing the procedure. I am not advocating RSB when there is absolutely nothing — there has to be something in the history, or other systemic findings, to warrant it. In that respect, I agree with the late Billy Preston (https://youtu.be/G_DV54ddNHE):

Nothin’ from nothin’ leaves nothin’
You gotta have somethin’ if you want to be with me

1. Pujol RM, et al. Invisible mycosis fungoides: A diagnostic challenge. J Am Acad Dermatol 2002; 47: (2 Suppl) S 168-71.
2. Brown SJ. Pseudoxanthoma elasticum: Biopsy of clinically normal skin in the investigation of patients with angioid streaks. Br J Dermatol 2007; 157; 748-51.
3. Stoddard H, et al. The performance of telescoping fat pad biopsies for detecting systemic amyloidosis: A four and a half year retrospective analysis and brief review of the fine needle aspiration literature. J Cutan Pathol 2016; 43: 637-42.
4. Gill S, et al. Use of random skin biopsy to diagnose intravascular lymphoma presenting as fever of unknown origin. Am J Med 2003; 114: 56-8.
5. Pongpudpunth M, et al. Usefulness of random skin biopsy as a diagnostic tool of intravascular lymphoma presenting with fever of unknown origin. Am J Dermatopathol 2015; 37: 686-90.
6. Sitthinamsuwan P, et al. Random skin biopsy in the diagnosis of intravascular lymphoma. J Cutan Pathol 2017; 44: 729-33.
7. Arai T, et al. Three cases of intravascular large B-cell lymphoma detected in a biopsy of skin lesions. Dermatology 2016; 232: 185-8.

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