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Subcutaneous Panniculitis-Like T-Cell Lymphoma With Granulomas as the Predominant Feature

Lee, Christine MD*; Hsi, Andy MD; Lazova, Rossitza MD

The American Journal of Dermatopathology: September 2019 - Volume 41 - Issue 9 - p 667–670
doi: 10.1097/DAD.0000000000001402
Extraordinary Case Report
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Abstract: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare primary cutaneous lymphoma preferentially localized in the subcutaneous adipose tissue and composed of cytotoxic T cells with an α/β immunophenotype. The neoplastic T cells can be variably admixed with other inflammatory cells, including histiocytes, which can rarely form noncaseating granulomas. We present a case of SPTCL in which granulomas are the predominant feature, composing 75%–80% of the inflammatory infiltrate. The top differential diagnoses included infectious and autoimmune etiologies. However, special stains for microorganisms were negative, and immunohistochemical analysis of the atypical lymphocytes showed a CD3+, CD8+, TIA-1+, T-cell receptor (TCR) beta+, and CD4 infiltrate with a high Ki67 proliferation index of approximately 30%. TCR gene rearrangement studies by polymerase chain reaction with confirmation by high-throughput sequencing were necessary to exclude an autoimmune etiology, specifically lupus erythematosus panniculitis. To the best of our knowledge, only 1 other case of SPTCL with prominent granulomas has been reported in the literature. It is important for dermatopathologists to recognize this presentation of SPTCL. SPTCL with predominant granulomas should be included in the differential diagnosis of granulomatous panniculitis along with infectious and autoimmune panniculitides as well as other granulomatous lymphomas.

*Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, CA; and

Department of Dermatopathology, California Skin Institute, San Jose, CA.

Correspondence: Christine Lee, MD, Department of Pathology and Laboratory Medicine, University of California, 10833 Le Conte Avenue, Los Angeles, CA 90095 (e-mail: christinemilee@gmail.com).

The authors declare no conflicts of interest.

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INTRODUCTION

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare primary cutaneous lymphoma predominantly involving the subcutaneous adipose tissue that is composed of cytotoxic CD8+ T cells with an α/β phenotype. Classic histopathologic appearance consists of a lobular infiltrate of atypical lymphocytes with medium-sized, mildly irregular, and hyperchromatic nuclei with moderate amounts of clear cytoplasm, focally rimming individual adipocytes in a lace-like pattern. The neoplastic lymphocytes can be variably admixed with other inflammatory cells, including histiocytes, which are often filled with karyorrhectic debris, scattered singly, in small clusters, or forming noncaseating granulomas.1 However, SPTCL with a predominant granulomatous component, defined as granulomas composing >25% of the inflammatory infiltrate, is rarely observed. To the best of our knowledge, only one other case has been reported in the literature and was initially misdiagnosed as granulomatous dermatitis. Granulomatous cutaneous lymphomas compose 1.8% of all primary or secondary cutaneous lymphomas and are commonly misdiagnosed as inflammatory or autoimmune dermatoses, which can delay an accurate diagnosis for a period ranging from 1 to 216 months.2 Therefore, it is important for dermatopathologists to know how to differentiate infectious and autoimmune granulomatous panniculitis from granulomatous lymphomas.

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Case Report

A 53-year-old woman with no significant medical history presented with a 3.5-cm enlarging and indurated mass on the right posterior upper arm. The skin overlying the mass was mildly edematous with no ulceration. The patient had no history of injection to this site. There were no other lesions on physical examination. Computed tomography imaging rendered an interpretation of soft-tissue edema with a differential diagnosis of soft-tissue contusion from trauma or cellulitis.

An excisional biopsy showed a densely cellular, lobular infiltrate in the subcutaneous fat with relatively minimal involvement of the fibrous septa on scanning magnification (Fig. 1). Granulomas consisting of histiocytes and multinucleated giant cells composed 75%–80% of the infiltrate (Figs. 2 and 3). Examination of the less prominent lymphocytic component revealed lymphocytes with medium-sized, hyperchromatic nuclei with irregular contours and scant cytoplasm that displayed rimming of individual adipocytes as well as focal disruption of adipocyte membranes (Fig. 4). Reactive lymphoid follicles and hyalinization of fat lobules were not observed. Furthermore, interface changes, basement membrane thickening, follicular plugging, and dermal mucin were absent.

FIGURE 1

FIGURE 1

FIGURE 2

FIGURE 2

FIGURE 3

FIGURE 3

FIGURE 4

FIGURE 4

Special stains for infectious organisms (acid-fast bacillus, Fite, Gomori methenamine silver, and Gram) were negative. Polarization microscopy for foreign material was also negative. Immunohistochemical analysis of the lymphocytic infiltrate showed that the neoplastic cells were cytotoxic T cells with the following immunophenotype: CD3+ (Fig. 5), CD8+ (Fig. 6), TIA-1+, and T-cell receptor (TCR) beta + T cells (not shown) with few CD4+ cells (Fig. 7). Scattered sparse, CD20+ B lymphocytes were identified in the background. CD163 highlighted the histiocytes in the predominant granulomatous component (Fig. 8). A Ki67 stain showed an increased proliferative index of approximately 30% with accentuation in the atypical lymphocytes around the adipocytes. There were scattered CD123+ plasmacytoid dendritic cells but no clusters. A diagnosis of SPTCL was rendered, which was confirmed by rearrangement of the TCR gamma gene on polymerase chain reaction (PCR) amplification. TCR high-throughput sequencing (HTS) was also performed, which revealed dominant sequences in the TCR beta and gamma regions. The patient received local radiotherapy and showed complete clinical resolution, confirmed by Positron emission tomography/computed tomography imaging.

FIGURE 5

FIGURE 5

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FIGURE 6

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FIGURE 8

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DISCUSSION

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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REFERENCES

1. Duncan LM, Baran JL, Ferry JA. Extranodal Lymphomas. Philadelphia, PA: Saunders; 2011:281–326.
2. Scarabello A, Leinweber B, Ardigó M, et al. Cutaneous lymphomas with prominent granulomatous reaction. Am J Surg Pathol. 2002;26:1259–1268.
3. Utino FL, Damiani GV, Garcia M, et al. Histomorphometric approach to differentiate skin lesions of tuberculoid leprosy from sarcoidosis. J Cutan Pathol. 2018;45:111–117.
4. Kempf W, Kazakov DV, Kutzner H. Lobular panniculitis due to Borrelia burgdorferi infection mimicking subcutaneous panniculitis-like T-cell lymphoma. Am J Dermatopathol. 2013;35:30–33.
5. Rabinowitz LO, Zaim MT. A clinicopathologic approach to granulomatous dermatoses. J Am Acad Dermatol. 1996;35:588–600.
6. Sharquie KE, Hameed AF, Noaimi AA. Panniculitis is a common unrecognized histopathological feature of cutaneous leishmaniasis. Indian J Pathol Microbiol. 2016;59:16–19.
7. Pfaltz K, Kerl K, Palmedo G, et al. Clonality in sarcoidosis, granuloma annulare, and granulomatous mycosis fungoides. Am J Dermatopathol. 2011;33:659–662.
8. Sharath HK, Gayathri MN, Bharathi M, et al. Isolated cutaneous sarcoidosis: a new insight into the old entity. J Clin Diagn Res. 2013;7:1725–1726.
9. Yoshida S, Fujimura T, Kambayashi Y, et al. Sarcoidosis-lymphoma syndrome associated with folliculotropic peripheral T cell lymphoma not otherwise specified. Case Rep Oncol. 2017;10:372–376.
10. Chalayer É, Bachy E, Occelli P, et al. Sarcoidosis and lymphoma: a comparative study. QJM. 2015;108:871–878.
11. Rea B, Haun P, Emerson R, et al. Role of high-throughput sequencing in the diagnosis of cutaneous T-cell lymphoma. J Clin Pathol. 2018;71:814–820.
12. LeBlanc RE, Tavallaee M, Kim YH, et al. Useful parameters for distinguishing subcutaneous panniculitis-like T-cell lymphoma from lupus erythematosus panniculitis. Am J Surg Pathol. 2016;40:745–754.
13. Chow KF, Ritchie E, Husain S, et al. Lethal T- and NK-cell lymphomas mimicking granulomatous panniculitidies: a clinicopathologic study of three cases. J Cutan Pathol. 2011;38:483–491.
Keywords:

subcutaneous panniculitis-like T-cell lymphoma; granulomas; infection; sarcoidosis; lupus erythematosus panniculitis

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