The predominant granulomatous component in this case of SPTCL overshadowed the minor component of atypical neoplastic lymphocytes and shifted the diagnostic differential to infectious and autoimmune etiologies. Depending on the clinical context, tuberculoid leprosy can be a serious diagnostic pitfall because the histopathology also shows well-defined, subcutaneous granulomas of epithelioid histiocytes with an evident lymphocyte rim. By contrast, the granulomas of tuberculoid leprosy tend to localize around appendages and nerves,3 which was not present in our case. In addition, the negative acid-fast bacillus and Fite stains made this diagnosis less likely. Other infectious agents that may produce a granulomatous panniculitis include Borrelia burgdorferi,4Coxiella burnetii,5 and Leishmania parasites.6 Lymphocytes in Borreliosis have been reported to have a cytotoxic immunophenotype similar to that seen in SPTCL. However, negative special stains also excluded this diagnosis.
The most frequent misdiagnosis of granulomatous cutaneous lymphoma is cutaneous sarcoidosis.7 Although the patient does not have clinical symptoms of systemic sarcoidosis, cutaneous sarcoidosis is still on the differential, as 5%–25% of cases have cutaneous involvement only.8 There are some histopathologic similarities between this case and typical cutaneous sarcoidosis, which can show granulomas composed of epithelioid histiocytes and multinucleated giant cells with a very minimal lymphocytic component. However, the granulomas are usually arranged back to back when approaching subcutaneous tissue. Also, there is no lymphocytic rimming of adipocytes in cutaneous sarcoidosis.3 Immunohistochemical studies can help to differentiate the 2 entities because the T cells in sarcoidosis are usually CD4+ and CD8−, whereas in SPTCL, the atypical lymphocytes are usually CD4− and CD8+. The absence of a classic sarcoidosis phenotype militated against this diagnosis and the possibility of concomitant sarcoidosis involving this specific site. However, the prominent granulomatous component raised the question of whether there might have been a history of undiagnosed sarcoidosis. Some authors believe there is a relationship between sarcoidosis and lymphoma, sometimes called sarcoidosis–lymphoma syndrome, in which patients with sarcoidosis are more likely to develop lymphoma or already have a concomitant lymphoma.9 This association is broadly explained by the immunologic microenvironment induced by tissue-associated macrophages, which are present in high numbers in granulomatous conditions. Tissue-associated macrophages have been found to secrete immunoreactive and immunosuppressive chemokines that can recruit cutaneous T-cell lymphomatous cells and promote the development of T-cell lymphomas.10
Rarely, cutaneous sarcoidosis, along with other inflammatory dermatoses, such as lupus erythematosus panniculitis (LEP), can exhibit clonality with PCR assays for TCR gene rearrangement.7 HTS is a more specific study than PCR and can be helpful in distinguishing reactive processes from lymphomatous entities.11 In this case, HTS was most useful in excluding the diagnosis of LEP. LEP and SPTCL have many overlapping histopathologic features, and it may be very difficult to differentiate the 2 diagnoses solely based on morphology. Scattered clusters of plasmacytic dendritic cells are more frequently seen in LEP but can also be seen in SPTCL, as in this case. Reactive lymphoid follicles and hyalinization of fat lobules are also features more typical of LEP. Classic features of cutaneous involvement by lupus; interface changes, basement membrane thickening, follicular plugging, and increased dermal mucin; although more common in LEP, can be seen in cases of SPTCL. Histopathological findings that favor SPTCL over LEP include atypical lymphocytes rimming adipocytes within an area of increased Ki67 proliferation index. LEP usually consists of bland lymphocytes that splay apart groups of adipocytes rather than rim them, and Ki67 is almost always <10%.12
Although our case demonstrated several histopathologic features consistent with SPTCL and lacked many of those usually associated with LEP, the presence of scattered plasmacytoid dendritic cells prevented a definitive exclusion of the latter diagnosis. Based on morphology alone, SPTCL could only be favored. Molecular confirmation with both PCR and HTS allowed for a confident diagnosis. Other cases of SPTCL also would likely require supportive molecular findings for a more definitive diagnosis because of the frequent overlap of histopathologic findings between SPTCL and LEP.
In addition, granuloma-predominant SPTCL can be a challenging diagnosis because the granulomas may obscure or draw attention from the atypical features of the lymphocytic infiltrate. There is the risk of missing aggressive lymphomas that can present as a granulomatous subcutaneous panniculitis, including extranasal natural killer/T-cell lymphoma, adult T-cell lymphoma, and cutaneous gamma/delta lymphoma.13 natural killer/T-cell lymphomas, unlike SPTCL, are almost always associated with Ebstein-Barr virus infection and often show prominent angiodestruction. SPTCL can also show lymphocytic vasculitis, although usually milder in extent, and karyorrhectic debris; so, immunohistochemical analysis of Ebstein-Barr virus expression is essential. Immunohistochemistry is also helpful in excluding cutaneous gamma/delta lymphoma, which shows a lymphocytic population that is CD56+, TIA-1-, and BF-1- with a gamma/delta phenotype, whereas SPTCL is almost always CD56− with an alpha/beta, cytotoxic phenotype. Adult T-cell leukemia/lymphomas typically show larger, more atypical CD4+ lymphocytes and are frequently associated with human T-lymphotrophic virus infection.
Granuloma-predominant SPTCL may encompass a broad differential including infectious, autoimmune, and other lymphomatous processes and may pose a diagnostic challenge, which can delay timely and accurate diagnosis. It is important for dermatopathologists to recognize that SPTCL can have a predominant granulomatous component and know how to overcome diagnostic pitfalls.
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Keywords:Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
subcutaneous panniculitis-like T-cell lymphoma; granulomas; infection; sarcoidosis; lupus erythematosus panniculitis