The precise incidence of γδ CTCL is unknown but this subtype accounts for <1% of all CTCLs and affects adults primarily, with most cases presenting between ages 50 and 60 years. A few pediatric cases have been reported,^6,7,8 including a 3-year-old.^6,7,8 Some series show a female predominance, but in others, males and females were equally affected.^8,9,10 While most patients in one large series were Caucasian, GDTCL is not restricted to this racial group.⁸ In the largest US series of PC GDTCL patients reported to date, associated comorbidities included autoimmune diseases, such as lupus erythematosus, other lymphoproliferative disorders, and other malignancies; and a small subset was associated with Epstein–Barr virus (EBV) expression (though the vast majority of PC GDTCL cases are EBV negative).

PC GDTCL is sporadic, and is not associated with specific genetic driver mutations. Precise etiology remains elusive, but immunosuppression and chronic antigenic stimulation may be risk factors for clonal expansion of γδ T cells.¹¹ Rarely, GDTCLs have been reported to arise in association with opportunistic infections in immunosuppressed patients,^12,13 or in the setting of immunosuppressive therapies.¹⁴ EBV infection may play a role in a small subset of these patients.¹⁵

The classical presentation of γδ CTCL is that of numerous or sometimes solitary or localized dermal and/or panniculitic pink or violaceous plaques that are frequently eroded, crusted, ulcerated, or necrotic. The median time of onset is approximately 2 months, with a range of 3 months to 20 years in one large series.⁸ These are most common on the lower extremities, but can affect the trunk, arms, and face (panniculitic presentation)⁹ (Figs. 17-1 and 17-2). Oral mucosal lesions have rarely been reported. Lesions may have epidermal change (scaling) and can mimic MF (Fig. 17-3) or psoriasis (Fig. 17-4), prior to becoming necrotic or ulcerated. Less commonly, it can mimic pyoderma or arthropod assault.⁸ Constitutional symptoms may be present and include low-grade fevers, chills, fatigue, and night sweats. Disease progression can result in spread to extracutaneous sites, including central nervous system. Gastrointestinal disease may be present at the time of skin diagnosis.⁸ Nodal and hepatosplenic involvement by lymphoma is less common, although there is a subtype of γδ lymphoma that specifically homes to the liver and spleen.

One distinct complication of the cytotoxic CTCLs is secondary hemophagocytic syndrome (HPS), more recently referred to as hemophagocytic lymphohistiocytosis (HLH).¹⁶ HLH is a result of over-activation of T cells and histiocytes in the reticuloendothelial system and presents with fever, hepatosplenomegaly, and lymphadenopathy. Lab tests will reveal pancytopenia, elevated lactate dehydrogenase (LDH), and liver function test elevations. Other abnormalities include elevated erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and ferritin. HLH is a poor prognostic sign, although the prognosis for PC GDTCL is poor even in the absence of HPS.⁹

The staging system used for γδ CTCL is different than that used for MF/Sézary syndrome. It is an anatomic staging system only (Tumor-Node-Metastasis) without any associated numeric staging.¹⁷

Optimal therapies for γδ CTCL are unknown although numerous skin-directed and systemic therapies have been published, with mixed response.^8,18,19,20 Systemic agents such as interferons and toll-like receptor agonists (imiquimod) should be avoided as they could stimulate further cytotoxicity of the tumor cells.

The prognosis of γδ CTCL is poor, with 5-year overall survival ranging from 0% to 34% in published studies.^3,8,9,10 A more recent retrospective series of 53 patients published by Guitart and colleagues demonstrated a 19.9% 5-year survival, with a median survival of 31 months. An MF-like clinical presentation followed a more indolent course when compared to the more aggressive panniculitic presentation.⁸ PC GDTCL can occasionally have an initially indolent course, but then switch to a more aggressive course.^{21,22,23,24,25}

Histologically, there is an infiltrate of atypical lymphocytes, with variable involvement of the dermis, epidermis, and subcutis. These histologic patterns may vary within the same patient and may be determined, in part, by the morphology of the lesion biopsied. The dermis is usually the epicenter, but a characteristic presentation of GDTCL is that of simultaneous epidermal, dermal, and subcutaneous involvement (Fig. 17-5). Perivascular, periadnexal, lichenoid, interstitial, nodular, and/or diffuse infiltrative patterns may be seen (Fig. 17-5). Extension into the subcutis is common. Karyorrhexis, necrosis, and emperipoesis can be observed. Similar to SPTCL, a lobular panniculitic infiltrate may demonstrate atypical T cells encircling the adipocytes (rimming) (Fig. 17-6). Epidermal involvement takes on a variety of patterns. The lymphocytes are frequently noted at the base of the epidermis, and may be associated with dyskeratosis, extravasation and exocytosis of erythrocytes and lymphocytes, or a vacuolar interface dermatitis similar to lupus erythematosus (LE) (Fig. 17-7). The epidermal pattern may mimic MF (although Pautrier microabscesses are absent). Epidermotropism may be strikingly pagetoid throughout the entire thickness of the epidermis, simulating pagetoid reticulosis or primary cutaneous AECTCL, and may involve adnexae. This latter presentation has been associated with gastrointestinal involvement.⁸ Evidence of cytotoxicity may be manifest by dermal, epidermal, and/or subcutaneous necrosis, karyorrhexis, erythrocyte extravasation, and vascular invasion with fibrinoid necrosis. Necrosis is especially prominent when accompanied by angiodestruction. Other findings that may be encountered include neurotropism and prominent mucin deposition (Fig. 17-8). γδ CTCL cytomorphology can be variable. Many cases show a monotonous infiltrate of medium-sized lymphocytes, while in other cases, pleomorphism is present, with the infiltrate being comprised of small, medium and/or large lymphocytes. The nuclei are irregular or elongate with indented chromatin-dense or vesicular nuclei and scant slightly granular cytoplasm⁸ (Fig. 17-9). Eosinophils and plasma cells are rarely seen, but may be present, especially if there is an adnexotropic component.⁸ A histiocytic component may be present, and at times may be granulomatous, mimicking an infectious process. Or the histiocytes may simulate a benign process, such as traumatic panniculitis (Fig. 17-10).