Benign inflammatory skin lesions are most likely to be confused with early patch-stage MF. In general, these conditions have clinical presentations and courses that are different from MF, lack enlarged atypical cerebriform T-cells, and lack epidermotropism that is disproportionately increased in relationship to spongiosis. However, in difficult cases, immunophenotypic analysis and gene rearrangement studies may be necessary to look for aberrant T-cell phenotypes or clonal TCR gene rearrangements. The benign inflammatory dermatoses that most closely resemble CTCL include small and LPP, PVA, pityriasis lichenoides, pigmented purpuric eruption, lichenoid keratosis, benign erythroderma, contact dermatitis, persistent arthropod bite reactions, drug eruptions, LyP, and actinic reticuloid (AR).²⁰⁵

Despite the name, the chronic skin diseases under the term parapsoriasis are unrelated to the much more common skin
disease psoriasis. Most dermatologists separate parapsoriasis into one of two types. The benign subtype is known as small plaque parapsoriasis, digitate dermatosis, or chronic superficial dermatitis. The other type is considered pre-malignant and is most often called LPP or parapsoriasis en plaques (having in the past been called pre-reticulotic poikiloderma).²⁰⁶, ²⁰⁷ LPP is clinically indistinguishable from patch-stage MF.¹²⁶ However, the patches of MF tend to be fixed whereas the patches of LPP tend to wane in the summer and flare in the winter. Because of clinical and histologic overlap, some authorities consider LPP to be an early stage of MF.²⁰⁸ Others consider LPP to be a latent form of MF²⁰⁹ because ˜10% of patients eventually develop overt MF.²¹⁰ A retrospective review documented a higher rate of evolution to MF in 12 of 36 (33%) patients with LPP.²¹¹ This view is supported by the demonstration of clonal TCR gene rearrangement in 50% of LPP biopsies.⁷³ Furthermore, demonstration of clonal TCR gene rearrangements in small plaque or digitate parapsoriasis has suggested that this may be an abortive form of MF.²¹², ²¹³ Histologically, the lymphoid infiltrate of LPP is perivascular and less dense with less epidermotropism than in MF; Pautrier microabscesses are not seen in LPP. Furthermore, cytologically atypical cerebriform T-cells with highly convoluted nuclei are inconspicuous or absent in LPP. However, immunophenotypic analysis is usually not helpful for differentiating LPP from patch-stage MF as both have a predominance of CD4⁺ helper cells with absent CD7 and CD62L expression.¹²⁷ One study found the presence of HECA-452 immunostaining higher in MF than LPP, which may be helpful in distinguishing the two diseases and predicting which cases of LPP may evolve into MF.²¹⁴

PVA can also present similarly to early MF, so much so, that most experts believe PVA to be a rare variant of MF.²¹⁵, ²¹⁶, ²¹⁷ The macules and patches of PVA show the poikilodermatous features of hypopigmentation, hyperpigmentation, atrophy, and telangiectasias. PVA macules/patches tend also to be localized to sun-protected sites, most commonly appearing on the buttocks, breasts, and flexural areas. And, like LPP, some clinicians believe that PVA may potentially precede or co-exist with MF.¹²⁵ Histologically, PVA is characterized by an atrophic epidermis, chronic, ill-defined inflammatory changes and dilated capillaries. Often, lymphoid cells form a bandlike pattern in the superficial dermis, with only rare epidermotropism.²¹⁵, ²¹⁶, ²¹⁷

Pityriasis lichenoides is considered a spectrum of diseases including an acute and a chronic form: pityriasis lichenoides et varioliformis acuta (PLEVA) and pityriasis lichenoides chronica (PLC), respectively. Many patients demonstrate lesions of both forms during their disease course. PLEVA, also known as Mucha-Habermann disease, is a benign cutaneous disorder characterized by recurrent, self-healing papulonecrotic lesions that may resemble LyP, which is discussed later.²¹⁸ PLC, which is a benign eruption with lymphocytic infiltrates of the skin, presents as a persistent, erythematous, papular eruption with scale.²¹⁹ Biopsies may show slightly atypical cerebriform T-cells with some epidermotropism, but vacuolar degeneration of the epidermal basilar layer, necrotic keratinocytes, and dermal hemorrhage in PLEVA distinguish it from MF. The lymphoid infiltrate is composed predominantly of CD8⁺ cells as opposed to the typical CD4⁺ phenotype of MF.²²⁰ The histology of PLC is similar to PLEVA, although the findings are muted with only focal basal vacuolar change and limited lymphocytic exocytosis. The intraepidermal lymphocytes tend to be CD4⁺, which further complicates the distinction from early MF. As in PLEVA, the lymphocytes lack significant cytologic atypia. Some consider pityriasis lichenoides to be a T-cell lymphoproliferative disorder or a form of indolent cutaneous T-cell dyscrasia related toLyP, and clonal TCR gene rearrangement has been demonstrated.²²¹, ²²², ²²³, ²²⁴ Although cases of patients with pityriasis lichenoides progressing to MF have been described, this is definitely a rare event.²²⁰, ²²⁴, ²²⁵

Pigmented purpuric dermatoses (PPD) are a group of chronic and benign skin disorders categorized by rupture of the small capillaries in the superficial papillary dermis. Clinically, patients present with petechiae and bronze discoloration of the skin on the lower extremities.²²⁶ Histologically, there is a superficial perivascular infiltrate that may be dense and lichenoid in nature. Dermal hemorrhage and hemosiderin deposition is present to varying degrees. Lymphocytic exocytosis is often present, however, cytologic atypia and intraepidermal lymphocytic microabscesses are generally absent. Immunohistochemical and molecular studies are typically not helpful in differentiating PPD from MF. Lichen aureus, a rare type of PPD, can mimic MF both clinically and histologically and progress to MF in very rare cases.²²⁷ One study showed that of 43 cases of PPD, 21 showed a clonal population of T-cells. Only 40% of the cases with demonstrated clonality, however, had clinical and pathologic features consistent with MF. In addition, loss of CD7 was frequently observed in both
the polyclonal and monoclonal groups.²²⁸ Other studies have documented the frequent occurrence of T-cell clonality in cases of PPD that fail to develop disease typical of MF.²²⁹ The presence of extensive PPD-like skin disease, especially when present outside the lower extremities, should raise the suspicion of MF regardless of the histologic features.

Lymphomatoid keratosis is a benign epithelial skin neoplasm related to an inflamed seborrheic keratosis or lichenoid keratosis. Patients generally demonstrate scattered small hyperkeratotic plaques on the trunk and are biopsied to rule out the possibility of a nonmelanoma skin cancer. The histologic features can be indistinguishable from MF with a lichenoid infiltrate and extensive lymphocytic exocytosis. Additionally, clonal populations of T-cells have been detected.²³⁰ The presence of epidermotropic CD20⁺ B-cells is suggestive of a lymphomatoid keratosis; however, clinicopathologic correlation is paramount in arriving at the correct diagnosis.²³¹

Erythroderma may occur in a variety of benign dermatologic disorders including psoriasis, pityriasis rubra pilaris, eczematous dermatitis, seborrheic dermatitis, severe contact dermatitis, and drug eruptions.²³², ²³³ These patients may also have circulating cerebriform cells and lymphadenopathy, further complicating the diagnosis. Erythroderma secondary to drug reactions, especially anticonvulsants such as phenytoin, can be particularly difficult to distinguish from MF/SS because of the presence of convoluted cerebriform T-cells and the formation of Pautrier microabscesses.¹⁴⁰ Several studies have compared the histologic features of erythrodermic MF/SS with other causes of reactive erythroderma. Although not present in all cases, Pautrier microabscesses and a dense, often lichenoid, dermal lymphocytic infiltrate were more commonly associated with erythrodermic MF/SS.²³⁴, ²³⁵, ²³⁶ Differentiation of benign erythroderma from erythrodermic CTCL can usually be accomplished through careful evaluation of the history, skin biopsy of the more typical lesions of the underlying disease, and molecular genetic analysis of both skin and blood.²³⁵, ²³⁶ Numerous eosinophils favor a drug reaction. Aberrant T phenotypes or clonal TCR gene rearrangements are usually not present in benign erythroderma.

Subacute or chronic spongiotic dermatitis and interface dermatitis resulting from contact dermatitis, drug eruption, and persistent arthropod bite reaction may have atypical cerebriform T-cells with epidermotropism and Pautrier-like microabscesses mimicking MF.²⁰⁵ Caution should be exercised in interpretation of epidermotropism associated with significant spongiosis, especially microvesiculation, which is only rarely observed in MF.¹⁴³ The Pautrier-like microabscesses seen in spongiotic processes typically have a flask shape and are composed of Langerhans cells and keratinocytes. Immunophenotyping may be helpful in this differential diagnosis because cutaneous T-cell pseudolymphomas rarely show aberrant loss of CD2, CD3, or CD5 expression, especially a combination of these markers.²⁰⁵ CD7 and CD62L (Leu 8) are not as helpful as their expression is commonly lost in both MF and reactive dermatoses.²⁰⁵ Typically, T-cell-predominant pseudolymphomas are characterized by perivascular, “sleevelike” infiltrates around vessels in the dermis, with accompanying plasma cells, eosinophils, and macrophages. The T-cells are typically a mixture of CD4⁺ and CD8⁺ cells as opposed to the CD4⁺-predominant population characteristic of most cases of MF. The utility of gene rearrangement studies in this setting is unclear as clonal TCR gene rearrangements have been reported in some cutaneous T-cell pseudolymphomas.²³⁷, ²³⁸, ²³⁹ The following drugs have been implicated as causing pseudolymphoma: alprazolam, amitriptyline, atenolol, carbamazepine, cefixime, chlorpromazine, cimetidine, clarithromycin, clonazepam, clonidine, cotrimoxazole, cyclosporine, desipramine, diltiazem, doxepin, fluoxetine, furosemide, gemfibrozil, gold, lamotrigine, lithium, lorazepam, losartan, methotrexate, nizatidine, perphenazine, phenytoin, ranitidine, sulfamethoxazole, sulfasalazine, and thioridazine.²⁴⁰

B-cell-predominant pseudolymphomas are notable for reactive follicle formation with tingible-body macrophages, centroblasts, and centrocytes in the germinal centers surrounded by distinct mantle zones. There are polyclonal plasma cells, a mix of CD4⁺ and CD8⁺ T-cells and often eosinophils in the accompanying inflammatory infiltrate.²⁴¹, ²⁴² CD21⁺ follicular dendritic cells (DCs) can be found in the follicles as well.

AR is a severe form of photosensitive dermatitis that may closely mimic MF or SS clinically and histologically when fully developed.²⁴³, ²⁴⁴, ²⁴⁵ AR is a chronic persistent eruption that can be induced by a broad spectrum of light wavelengths (ultraviolet A [UVA], UVB, and visible wavelengths of light).²⁴³ The skin lesions are typically plaques and papules on the sun-exposed areas of the face and hands, but may extend to covered areas or even become generalized erythroderma.²⁴⁶ In contrast to MF, epidermotropism is not prominent, but small Pautrier microabscesses may be found in some cases. Severe cases of erythrodermic AR may have generalized lymphadenopathy and circulating Sézary cells mimicking SS. Preferential involvement of sun-exposed areas, absence of large dysplastic cerebriform T-cells, and a CD8⁺ phenotype help distinguish AR from MF/SS. AR does not appear to be associated with progression to malignant lymphoma, and clonal TCR rearrangements have not been reported.²⁴⁵

The differential diagnosis for suspected MF also includes a variety of related conditions, which are equally concerning for their malignant or pre-malignant clinical course. LyP and primary cutaneous ALCL (pcALCL) are both characterized by the presence of CD30⁺ T-cells; together, they represent the poles of a continuous disease spectrum. Both LyP and pcALCL are now considered subtypes of the CTCLs.¹³⁷ There is no clear-cut boundary between the diseases, however, and many patients fall into a borderline category when definitive diagnosis is not possible based on the current clinicopathologic features.

LyP is a CD30 (Ki-1)-positive T-cell lymphoproliferative disorder characterized by chronically recurring, self-healing crops of mildly pruritic papulonodular lesions that are clinically benign but histologically malignant.²⁴⁷ LyP initially presents with crops of erythematous papules that wax and wane, becoming hemorrhagic and necrotic before undergoing spontaneous regression with scar formation. Individual lesions range from 2 mm to 2 cm in diameter (usually <1 cm) and have an average duration of 5 weeks, ranging from 2 weeks to 6 months.²⁴⁸ LyP is classically divided into three histologic types, type A, type B, and type C. More recently a fourth histologic presentation, termed LyP type D, has been described.²⁴⁹ Any of the histologic types may occur simultaneously in the same patient or during the course of the disease and the individual histologic type provides no prognostic significance.²⁵⁰ LyP type A, the most common type, is characterized by a polymorphous infiltrate of eosinophils, neutrophils, and scattered anaplastic large transformed lymphocytes and binucleate Reed-Sternberg-like cells (Fig. 92.9).²⁵¹, ²⁵² LyP type B is characterized by small to medium cerebriform T-cells resembling MF. LyP type C is characterized by sheets of large, anaplastic CD30⁺ cells and can be histologically identical to pcALCL but follows a waxing and waning clinical course. The atypical cells in LyP types A, B, and C are typically CD4⁺. LyP type D is characterized by an extensively epidermotropic population of cytologically atypical CD8⁺ lymphocytes in a pattern that is nearly identical to that observed in primary cutaneous aggressive epidermotropic CD8⁺ cytotoxic T-cell lymphoma (see below).²⁴⁹, ²⁵³, ²⁵⁴ The atypical cells in all of the types often have clonal rearrangement of the T-cell-receptor gene, and absent or diminished expression of pan-T-cell antigens.²⁵⁵ However, CD30 expression differs among the types; the large transformed cells in types A, C, and D are CD30⁺, similar to CD30⁺ ALCL, whereas the atypical cerebriform T-cells in type
B LyP typically do not express CD30.²⁵⁶ Vonderheid and Kadin have suggested that the papular variant of MF and type B LyP are the same entity²⁵⁶ although Kodama and colleagues point to the lack of spontaneous resolution of papules in papular MF.²⁵⁷ Clinical behavior of LyP is usually benign; however, overt lymphoma has been documented in ˜10% to 25% of patients, usually MF, pcALCL, or Hodgkin lymphoma.²⁴⁸, ²⁵⁸ The cumulative risk for the development of another lymphoma in patients with LyP over 15 years of disease may be as high as 80%.²⁵⁹ A retrospective review of 31 patients with LyP over a 27-year span identified 60% who developed a co-existing lymphoma.²⁵⁸ No clinical, histologic, immunophenotypic, or molecular genetic features have been identified that can predict which patients will develop lymphoma, but two studies suggest that malignant transformation is more strongly associated with type A than with type B LyP.²⁵⁶ Onset of LyP at a younger age may be associated with increased cumulative risk for overt lymphoma and therefore all LyP patients should be closely monitored throughout their lives.²²¹, ²⁵⁹, ²⁶⁰ The benign or malignant nature of LyP is controversial, but the WHO-EORTC considers LyP to be a latent or low-grade stage of the primary cutaneous CD30⁺ lymphoproliferative disorders that are considered to be malignancies.¹³⁷, ²⁶¹ Its clinical, histologic, and immunophenotypic similarities to pcALCL, aberrant T-cell-antigen expression, clonal TCR gene rearrangements, and increased risk for transformation to malignant lymphoma support this view.

Differentiation of primary cutaneous ALCL from LyP and secondary CD30⁺ LCL resulting from large-cell transformation of MF/SS is important because of differences in prognosis and therapy.¹³⁷, ²⁶¹ pcALCL has a good prognosis and can be effectively managed with local excision and/or radiation therapy,²⁶² whereas secondary CD30⁺ LCL due to large-cell transformation of MF/SS has a very poor prognosis requiring systemic therapy that often includes aggressive combination chemotherapy.¹⁶⁷, ²⁶³ LyP also has an excellent prognosis and can often be managed with no therapy, topical chemotherapy, phototherapy, and low-dose methotrexate without the need for aggressive therapy.²⁶⁴, ²⁶⁵ Furthermore, pcALCL must be differentiated from secondary cutaneous involvement by extracutaneous ALCL.²⁶⁶, ²⁶⁷ Primary nodal ALCL and secondary cutaneous involvement by extracutaneous ALCL are more aggressive than pcALCL.²⁶⁶, ²⁶⁷ In malignant cells, the presence of anaplastic lymphoma kinase-1 protein (ALK-1) from the t(2;5) (p23;q35) chromosomal translocation favors primary nodal ALCL.²⁶⁸ A thorough dermatologic examination, history, and staging for extracutaneous disease are necessary to exclude secondary large-cell transformation of low-grade MF or secondary cutaneous involvement by extracutaneous lymphoma before a case is accepted as pcALCL. pcALCL is differentiated from LyP type A by cohesive sheets or >75% CD30⁺ large transformed cells, fewer admixed neutrophils and eosinophils, a diffuse infiltrate that extends into the deep dermis versus a more superficial wedge-shaped infiltrate, larger solitary or localized nodules or tumors instead of crops of papules, and higher frequency of persistent or progressive cutaneous lesions with less frequent or incomplete spontaneous regression.²⁶³, ²⁶⁸, ²⁶⁹ Recently it has been shown that translocations in the interferon regulatory factor-4 (IRF4) gene are specifically associated with pcALCL and may be used to differentiate it from the other previously mentioned entities.²⁷⁰ Other aspects of ALCL are discussed in more detail in Chapter 88.

Using the WHO-EORTC classification for cutaneous lymphomas as a guide, other primary CTCLs need to be considered in patients with atypical lymphocytic infiltrates of the skin.¹³⁷, ¹³⁹, ²⁷¹ These lymphomas include: three variants of MF (pagetoid reticulosis [PR], granulomatous slack skin [GSS] disease, and folliculotropic MF); subcutaneous panniculitic T-cell lymphoma; extranodal NK-/T-cell lymphoma, nasal type; and primary cutaneous peripheral T-cell lymphomas (PTCLs), unspecified, which include: (a) primary cutaneous aggressive epidermotropic CD8⁺ T-cell lymphoma, (b) CGDTCL, and (c) primary cutaneous CD4⁺ small/medium-sized pleomorphic T-cell lymphoma.

PR and folliculotropic MF are variants of MF implying minor clinicopathologic differences from classical MF, whereas GSS is a subtype of MF with more significant differences from classical MF.²⁷² As in classical MF, these diseases are low-grade clonal T-cell lymphomas that generally follow a benign course but may behave aggressively over time. PR is a rare epidermotropic variant of MF that usually presents as localized, hyperkeratotic, verrucous plaques on the hands or feet (Woringer-Kolopp disease)²⁷³ but may also present with disseminated cutaneous plaques (Ketron-Goodman disease).²⁷⁴ Given its more aggressive clinical course, Ketron-Goodman disease would currently be better classified as tumor-stage MF, CGDTCL, or aggressive epidermotropic CD8⁺ CTCL.¹³⁷, ²⁷⁵, ²⁷⁶ PR may mimic a more unusual variant of MF localized to the palms and soles known as MF palmaris et plantaris.²⁷⁷ Skin biopsies of PR show pagetoid epidermotropism by enlarged, atypical cerebriform T-cells, with relative sparing of the dermis (Fig. 92.10). The malignant cells in PR may be CD8⁺ or, less commonly, CD4⁺and rarely, CD4^–CD8^–.²⁷⁸ In contrast to conventional MF and SS, there is often co-expression of CD30⁺. Although the original classification of PR allowed for γδ TCR expression of the neoplastic cells, these cases are best classified
as CGDTCL according to the WHO-EORTC guidelines. Clonal TCR gene rearrangement and aberrant T-cell-antigen expression support classification of PR as a form of CTCL;²⁷⁹ however, PR has a clinically benign course, with only rare reports of cutaneous dissemination of localized PR.²⁷⁶ Further studies are needed to confirm whether phenotypic differences in PR have clinical relevance. Local excision or radiation therapy is generally adequate treatment for PR, especially the localized form.

Folliculotropic or follicular MF (FMF) is another uncommon variant of CTCL first reported in 1985 with preferential perifollicular and folliculotropic infiltration by atypical cerebriform T-cells with minimal or absent epidermotropism and mucin (Fig. 92.11).²⁸⁰, ²⁸¹, ²⁸² The follicles may show plugging, cystic dilatation, and mucinous degeneration, as seen with mucin stains such as Alcian blue. Folliculotropic cerebriform T-cells are CD4⁺²⁸², ²⁸³ and may express an aberrant T-cell phenotype with loss of CD7 and other T-cell antigens.²⁸² Differential up-regulation of ICAM-1 (CD54) on follicular epithelium instead of epidermal keratinocytes has been implicated in the folliculotropic homing pattern of folliculotropic MF.²⁸² Lymph node involvement and large cell transformation have also been described.²⁸² Folliculotropic MF, whether or not exhibiting follicular mucinosis, has shown a more aggressive course than classic MF.¹⁸⁹, ²⁸⁴ Approximately 7% of reported cases have demonstrated rapid lymph node involvement.²⁸⁵, ²⁸⁶ In a large series of patients with FMF (n = 51), the disease-specific survival was 68% at 5 years and 26% at 10 years.²⁸⁶ This poor prognosis has been confirmed by other studies as well.¹⁶⁶, ²⁸⁷ Agar and colleagues completed an outcome analysis on 1,502 patients with MF/SS concluding that folliculotropic MF was one of several independent predictors of poor survival and increased risk of disease progression.¹⁸⁹

Follicular mucinosis is frequently associated with folliculotropic MF and less commonly with classical MF. This variant of MF must be differentiated from idiopathic follicular mucinosis or alopecia mucinosa.²⁸⁸, ²⁸⁹ In general, no single clinicopathologic feature can differentiate follicular mucinosis associated with MF from alopecia mucinosa.²⁸⁸, ²⁸⁹, ²⁹⁰ Alopecia mucinosa tends to occur in younger patients with fewer lesions localized to the head and neck as opposed to the more general distribution commonly seen in MF-associated cases. Histologically, alopecia mucinosa tends to have fewer atypical cerebriform T-cells, less epidermotropism and/or lymphocytic infiltration of follicular epithelium, and a normal CD4/CD8 ratio. In follicular mucinosis associated with MF the infiltrate tends to be denser and cytologically atypical with a CD4⁺-predominant immunophenotype.²⁸⁸ Clonal TCR gene rearrangement can be detected in many cases of alopecia mucinosa thus limiting its usefulness in the differentiation from MF.²⁹⁰, ²⁹¹ In support of this, a long-term follow-up study of seven patients with follicular mucinosis concluded that despite the presence of a clonal TCR gene rearrangement, there was no evidence of progression to CTCL in any patient.²⁹²

GSS disease is a rare but distinctive subtype of MF that begins with patches and plaques that steadily progress to characteristic pendulous, erythematous skin folds in the axillae and groin.²⁹³, ²⁹⁴, ²⁹⁵, ²⁹⁶, ²⁹⁷, ²⁹⁸ Several authors stress the importance of distinguishing the mature lesions of GSS from the histologic variant of granulomatous MF, which can be differentiated quantitatively, not qualitatively.²⁹³, ²⁹⁸ GSS has histologic features of MF including superficial papillary dermal and epidermotropic infiltrates of atypical cerebriform T-cells, but it also exhibits expansive infiltration into the deep dermis and subcutis with extensive elastolysis and a prominent granulomatous reaction with Langerhans-type multinucleated giant cells (Fig. 92.12). These multinucleated giant cells are histiocytic in origin with 20 to 30 nuclei, frequently show emperipolesis and elastophagocytosis, and express CD68 and CD1a.²⁹³, ²⁹⁹, ³⁰⁰ Similar to MF, GSS is a clonal proliferation of CD4⁺ T-helper cells that frequently lack expression of CD7 and CD62L. GSS usually remains localized to the skin, although hypercalcemia, lymph node involvement, and fatal systemic dissemination have been reported.²⁹⁵, ²⁹⁶, ²⁹⁷, ²⁹⁸, ³⁰¹, ³⁰² It is important to note that in contrast to other CTCL variants, patients with GSS have an increased incidence of Hodgkin lymphoma at a frequency between 25% to 50%.²⁹³, ³⁰², ³⁰³

Subcutaneous panniculitis-like T-cell lymphoma (SPTL) presents as tender erythematous nodules or subcutaneous palpable masses, mostly on the legs, trunk, arms, or face. Histologically, this lesion is confined to the subcutis and does not typically
extend to the dermis or epidermis.³⁰⁴, ³⁰⁵ Classically, T-cells ranging from small and inconspicuous to large and transformed cells with hyperchromatic nuclei rim individual fat cells.³⁰⁶, ³⁰⁷ There is necrosis, karyorrhexis, and cytophagocytosis by the histiocytes that are found interspersed in the lesional tissue. As the name implies, this lymphoma is similar in histology to a lobular panniculitis and, in fact, many patients present with a history of previously biopsied panniculitis. In addition, there is some clinical and histologic overlap with lupus panniculitis and many patients with SPTL will present with or develop evidence of concomitant systemic lupus erythematosus.³⁰⁸, ³⁰⁹, ³¹⁰ By immunohistochemistry, the neoplastic T-cells express αβ TCR, CD3, CD8, and cytotoxic granule proteins, although CD56 and CD30 are rarely detected.³⁰⁴, ³⁰⁶, ³⁰⁷, ³¹¹, ³¹² Historically SPTL had been associated with a very poor prognosis often secondary to an aggressive hemophagocytic syndrome (HPS). The more recent WHO-EORTC classifications divided these cases into SPTL with an αβ phenotype and CGDTCL based both on immunohistologic features and clinical behavior. SPTL with an αβ phenotype are CD4^–, CD8⁺, CD56^–, and βF1⁺; are limited to the subcutaneous fat; are uncommonly associated with a HPS; and have a favorable prognosis (5-year OS 82%). CGDTCL is generally CD4^–, CD8^–, CD56⁺/-, and βF1^–; tends to involve the epidermis with resulting ulceration; is commonly associated with HPS; and has a dire prognosis (5-year OS 11%).³¹³ Repeat biopsies may be necessary to confirm the diagnosis of SPTL. Once confirmed, early induction of combination chemotherapy with or without radiotherapy may yield remission and prevent the development of HPS.³¹⁴, ³¹⁵, ³¹⁶ (For further discussion of SPTL, see Chapter 88.)