Mycosis Fungoides
Amy C. Musiek
Alejandro A. Gru
András Schaffer
DEFINITION
Mycosis fungoides (MF) is the most common form of primary cutaneous T-cell lymphoma (CTCL) characterized by epidermotropic small-to-medium–sized T lymphocytes with cerebriform nuclei. It exhibits a protracted clinical course with slow progression from slightly scaly skin lesions (patches) to infiltrated plaques and tumors. In its later stages, the disease can progress to a leukemic phase with erythroderma and systemic spread to lymph nodes, bone marrow, and visceral organs. The prototypical immunophenotype is that of CD3+CD4+CD8−CD7−. Expression of CCR4, CLA (CD45), and lack of CCR7/L-selectin molecules suggests that MF is a malignancy of mature skin-homing effector memory T “helper” (TH) cells. MF often shows significant clinical and histopathologic overlap with selected inflammatory dermatoses and other cutaneous lymphomas, including primary cutaneous anaplastic large cell lymphoma (C-ALCL) and adult T-cell leukemia/lymphoma, a mature T-cell lymphoma caused by the retrovirus human T-lymphotropic virus 1 (HTLV-1). According to the current World Health Organization (WHO) and European Organization for Research and Treatment of Cancer (EORTC) classification systems, the term MF should be restricted to cases exhibiting the classical evolution of patches, plaques, and tumors.
EPIDEMIOLOGY
Cutaneous lymphomas are classified as non-Hodgkin lymphomas and are a heterogeneous group of diseases. The skin is the second most common site for extranodal non-Hodgkin lymphomas after the gastrointestinal tract.1 The actual epidemiology of MF is difficult to assess, given that the disease is underdiagnosed and often difficult to classify. In the United States, epidemiologic data obtained from two studies examining the Surveillance, Epidemiology, and End Results Program (SEER) database, which account for approximately 25% of the population, are generally concordant with one another and show a largely similar epidemiology. These studies show that the incidence of CTCL is 6.4 per million persons, with MF accounting for greater than 50% of all CTCLs.2 MF has a male predominance and is slightly more common among black patients.3 The median age at presentation is 57 years.4 The incidence rate increases with age and peaks at 80 years of age. The male and black predominance also increase with increasing age.3 MF in children and adolescents is rare, lacks obvious racial predilection, and often presents in patients with Fitzpatrick skin type III or greater.5
ETIOLOGY
The etiopathogenesis of MF is only partially understood. It has been suggested that oncogenic transformation of MF might stem from chronic antigenic stimulation to viruses or bacterial superantigens in genetically susceptible hosts. While no single etiologic factor fully explains the occurrence of MF, several environmental and immunogenetic factors have been implicated. The geographical clustering of the disease strongly implies a role for external factors as a possible trigger.6 Infectious agents, such as Staphylococcus aureus, Ebstein-Barr virus, human T-lymphotropic virus, and human herpesvirus-8, have been implicated.7 The role of a transmissible agent is also supported by reports showing the transmission of the disease in bone marrow recipients, as well as across nonblood-related family members.8,9
The role of immunogenetic factors in MF pathogenesis is suggested by reports of disease clustering in first-degree relatives harboring certain human leukocyte antigen (HLA) alleles.10,11 Furthermore, increased representation of specific HLA-I and HLA-II antigens in sporadic cases has also been reported.12,13,14
Recent data have shown that MF and Sézary syndrome likely originate from two different precursors. The expression of CD3, CD4, CCR4, and CLA but not CCR7 by MF suggests its derivation from mature skin-homing effector memory TH cells.15 This is in contrast to Sézary syndrome, in which cells are CCR7+, similar to those of central memory T-cells.15
In MF, the malignant clone’s cell surface molecules are skin homing, as CLA binds E-selectin on cutaneous vascular endothelial cells and CCR4 binds the keratinocyte-manufactured chemokines CC-chemokine ligand 17 and 22.15 These interactions give the malignant T-cell clone access to the epidermis. Other chemokine receptors expressed in MF include CCR10, CXCR3, and CXCR4, and other cell surface molecules include integrin αE/β7 and LFA-1.16,17,18 Basal keratinocytes, Langerhans cells, and endothelial cells all express ligands for these receptors.
The proliferation of the malignant T-cell clone can be explained by several mechanisms. These include the expression of CD45RO, proliferating-cell nuclear antigen, and CD25 as well as the constitutive activation of the JAK/STAT pathway.19,20 A variety of mutations in the Fas/FasL system found in MF lead to a nonfunctional Fas protein, which may confer resistance to apoptosis.21 The expansion of malignant T-cell clone results in the restriction of the T-cell repertoire, leading to immunodeficiency even in the early stages of the disease.19
Finally, the hallmark of MF is immune dysregulation. The malignant clone in MF exhibits a TH1 phenotype in the early patch stage.22 As the disease progresses, neoplastic clones show a mixed TH1 and TH2 phenotype in plaques, and complete TH2 predominance in tumors (Fig. 12-1). The expression of TH2 cytokines IL-4, IL-5, and IL-10 causes a decrease in TH1 effects, cell-mediated immunity, and dendritic cells, thus propagating further immune dysregulation. The TH2-mediated increase in IgE and eosinophilia leads to the allergic phenotype often seen in erythrodermic MF. Correcting these defects provides a proven therapeutic target.
 FIGURE 12-1. Histopathology, immune dysregulation, and differential diagnosis in MF progression. In patch stage, CD4+ malignant T-cells exhibit a TH1 phenotype and home to the epidermis. In plaques, neoplastic T-cells expand in both the epidermis and dermis, have mixed TH1 and TH2 phenotypes, and form Pautrier microabscesses as they rosette around epidermal Langerhans cells. In tumor stage, epidermotropism is minimal, tumor cells are primarily TH2 skewed, and occupy the dermis and subcutaneous tissue. Large cell transformation occurs mostly in tumors and less frequently in plaques. Systemic spread of malignant T-cells in erythrodermic MF leads to suppressed host immune responses. The presence of plasma cells and eosinophils in plaques and tumors is likely reflective of TH1 to TH2 immune effector switch by neoplastic cells. PLC, pityriasis lichenoides chronica; PC-ALCL, primary cutaneous anaplastic large cell lymphoma; PC-PTCL-NOS, primary cutaneous peripheral T-cell lymphoma, not otherwise specified; SMPTL, primary cutaneous CD4+ small/medium pleomorphic T-cell lymphoma; PRP; pityriasis rubra pilaris. |
CLINICAL PRESENTATION AND PROGNOSIS
The clinical presentation of MF is often characteristic of the disease variant and clinical stage. Conventional MF typically presents on the trunk and buttocks. The most common site of involvement of folliculotropic MF (FTMF) is the head, neck, and upper back. Syringotropic MF (STMF) as well as solitary pagetoid reticulosis has predilections for the distal extremities (Fig. 12-2).
 FIGURE 12-2. Anatomical site predilections of MF variants. |
Patch Stage Mycosis Fungoides
Patch stage or early stage MF appears as large, greater than 5 cm, scaly patches in non–sun-exposed skin (Fig. 12-3A). MF can appear erythematous, hyperpigmented, or hypopigmented. Poikilodermatous features may also be present. The clinical differential diagnosis includes both eczematous dermatitis and parapsoriasis.23 Patients with patches or plaques covering less than 10% of their body surface area (T1) have a 5-year disease-specific survival of 98%, while patients with patches or plaques covering greater than 10% of their body surface (T2) area have a 5-year disease-specific survival of 89%. Both have a low rate of disease progression of 8% and 21%, respectively.24
 FIGURE 12-3. Conventional MF. A. Erythematous scaly patches on sun-protected skin. B. Erythematous scaly plaques, some with ulceration. C. Tumor stage MF. |
Plaque Stage Mycosis Fungoides
Clinically, plaque stage MF is very similar to patch stage MF, with patients presenting with patches that become more indurated and well defined over time; ulceration may occur (Fig. 12-3B).23 Although the staging system does not differentiate between patches and plaques for patients with a clinical stage of T2, plaque stage disease is associated with worse disease-specific survival and a higher risk of disease progression.24
Tumor Stage Mycosis Fungoides Without Large Cell Transformation
Tumors of MF are described as erythematous nodules greater than 1 cm. They can occur in the setting of patch/plaque disease or as tumor d’emblee. Tumor stage disease (T3) is considered late stage disease (Fig. 12-3C).25 Disease-specific survival drops considerably to 52%, and the risk of disease progression is 51%.
HISTOLOGY
Patch Stage Mycosis Fungoides
The histopathology of early MF varies greatly and can have significant overlaps with inflammatory mimics. To reach the diagnosis of MF at an early stage, slight perturbations in the microanatomical distribution of lymphocytes, nuclear atypia of lymphocytes, and changes in the epidermis and papillary dermis have to be accounted for (Table 12-1).
TABLE 12-1 Histologic Spectrum of Patch Stage MF | |||||||||||||||||||||
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In early patch stage, lymphocytic infiltrates are scant, patchy, and the epidermis and papillary dermis are only minimally altered. Recognition of epidermal colonization by rare single or clustered neoplastic lymphocytes with minimal cytologic atypia and surrounding lacunae is the only diagnostic clue at this stage of the disease (Fig. 12-4).26,27
 FIGURE 12-4. Early patch stage MF. A and B. Scant lymphocytic infiltrates in the papillary dermis. The epidermis shows irregular rete and hyperkeratosis. C. Arrow indicates a rare epidermotropic lymphocyte with nuclear hyperchromasia and perinuclear halo (“coal on a pillow”). Magnifications: A, 15x; B, 50x; C, 200x. |
In late patch stage, epidermotropism is more pronounced. Alignment of atypical lymphocytes at the dermal–epidermal junction (tagging), as well as pagetoid scatter within the epidermis, are pathognomonic (Fig. 12-5).28,29 To clarify terminology, it should be noted that epidermotropism is used to describe neoplastic T-cell migration into the epidermis, as opposed to lymphocytic exocytosis, which is a term referring to intraepidermal lymphocytes in inflammatory dermatoses. Epidermotropism in MF, in contrast to lymphocytic exocytosis in dermatitis, is generally devoid of vacuolar changes, dyskeratosis, or spongiosis.
 FIGURE 12-5. Late patch stage MF. A. Increased number of lymphoid infiltrates in the papillary dermis. B and C. Increased epidermal colonization by hyperchromatic neoplastic lymphocytes with perinuclear halo. Neoplastic cells lining-up along the dermoepidermal junction. Magnifications: A, 15x; B, 50x; C, 200x. |
Epidermal changes in early MF are usually minimal and typically exhibit three distinct patterns. Spongiosis, or edema between keratinocytes, is usually subtle around neoplastic cells in MF than in reactive spongiotic dermatitides. Psoriasiform changes with thickening, and elongation of the rete may be occasionally seen in MF. This is likely due to the skewed TH1 cytokine production by epidermotropic neoplastic T-cells, which in turn promotes keratinocyte growth in a fashion similar to that seen in psoriasis, a classic TH1-driven disease (Fig. 12-6A). Irregular rete elongation or fusion of retes can also be observed (Fig. 12-6B). In chronic lesions, MF may exhibit epidermal atrophy with thinning of the epidermis and effaced rete, which is likely a reflection of disturbed epidermal differentiation and/or cytotoxicity exerted by neoplastic T-cells (Fig. 12-6C).
 FIGURE 12-6. Epidermal changes in MF. A. Psoriasiform epidermal hyperplasia. B. Irregular rete alteration. C. Epidermal atrophy. |
As patch stage MF progresses, neoplastic T-cells begin to reveal cytologic atypia including characteristic hyperchromatic nuclei with deep narrow indentations and cerebriform contours (Fig. 12-7). However, one cannot solely rely on nuclear features in differentiating malignant from benign T-cells as nuclear atypia does not equate to transformation. A subset of reactive T-cells with CD4+CD26− immunophenotype show similar “atypical” morphology with cerebriform features.30
 FIGURE 12-7. Cytologic features of epidermotropic lymphocytes in MF. Neoplastic lymphocytes are small to medium in size, exhibit hyperchromasia and cerebriform nuclei. |
Recognizing subtle histopathologic changes in the papillary dermis could provide additional useful cues for the diagnosis of early MF. Assessing the degree of solar elastosis is helpful in differentiating neoplastic from reactive lymphocytic infiltrates: classic MF lesions occur at sun-protected sites; thus, the presence of prominent solar elastosis would militate against T-cell neoplasia. An exception to this rule is FTMF, which typically occurs on sun-exposed sites such as the face and head. Other dermal hallmarks of patch stage MF are related to fibrotic changes elicited by chronically retained neoplastic cells in the papillary dermis (“signs of chronicity”). These changes typically occur in late but not in early patch stage MF and include: (1) conversion of the papillary dermal collagen from fine fibrillary forms into wiry collagen bundles (fettuccine-like fibrosis) and (2) “halo” formation around lymphocytes (Fig. 12-8).28,29,31,32
 FIGURE 12-8. Papillary dermal alterations in MF: wiry collagen thickening (fettuccine-like fibrosis) and halo formation around lymphocytes. |
Plaque Stage Mycosis Fungoides
Progression of MF from patch stage is accompanied by the expansion of neoplastic T-cells both in the epidermis and dermis, contributing to the clinical presentation of raised, palpable plaques (Figs. 12-1, 12-3B, and 12-9A,B). In the epidermis, expanded neoplastic T-cells aggregate and rosette around CD1a+ Langerhans cells to form so-called Pautrier abscess (Fig. 12-10A,B). These neoplastic T-cell rosettes have to be distinguished from Langerhans cell microgranulomas, also known as pseudo-Pautrier abscesses, that are commonly associated with contact/eczematous dermatitides (Fig. 12-11).33 In the dermis of plaque stage MF, neoplastic T-cells form broad, band-like infiltrates that extend from the papillary into the superficial reticular dermis. In both the plaque and tumor stages, it is not infrequent to observe admixed inflammatory cells, such as eosinophils and plasma cells (Fig. 12-1). This is likely a consequence of a switch in immune effector function from TH1 to TH2 during disease progression.
 FIGURE 12-9. Histopathology of plaque stage MF. Neoplastic lymphocytes expand both in the epidermis and dermis. Magnifications: A, 15x; B, 50x. |
 FIGURE 12-10. Pautrier microabscess. A. Neoplastic cells are grouped within the epidermis. B. The microabscess is centered around CD1a+ Langerhans cells. |
 FIGURE 12-11. Vase-shaped Langerhans cell microgranuloma (pseudo-Pautrier microabscess) in spongiotic dermatitis. |
Tumor Stage Mycosis Fungoides With or Without Large Cell Transformation
The clinical emergence of tumors and nodules at late disease stages correlates with loss of epidermotropism and nodular or sheet-like expansion of neoplastic T-cells in the reticular dermis (Figs. 12-1 and 12-12A–D). Cytologic atypia is readily discernible as neoplastic cells markedly outnumber admixed reactive T-cells that are presumed to have antitumoral activity. Neoplastic T-cells may undergo large cell transformation (LCT), which is defined when neoplastic cells four times the size of normal lymphocytes constitute more than 25% of the infiltrate. LCT is not restricted to tumor stage disease, as plaque and very rare instances of transformed patch stage cases have been reported.34,35 This transformation event portends poor prognosis.36,37 The morphology of large transformed cells varies from cells with large hyperchromatic, vesicular nuclei and scant cytoplasm to cells with large irregular nuclei, prominent nucleoli, and abundant cytoplasms, characteristic of anaplastic large cell lymphoma. Differentiating MF with large cell transformation from primary cutaneous anaplastic T-cell lymphoma is histologically unfeasible, and requires immunophenotyping and clinical correlation with preexisting patches or plaques.22
 FIGURE 12-12. Histopathology of tumor stage MF. A-C. Minimal epidermotropism and diffuse dermal infiltration with subcutaneous involvement. D. Large cell transformation. Note admixed plasma cells and eosinophils. |
Staging and Extracutaneous Spread
Clinical/prognostic stratification of MF is determined by cutaneous tumor burden, presence of lymph node involvement, visceral metastasis, and peripheral blood involvement. These parameters are recorded in the tumor–node–metastasis (TNM) staging system (Tables 12-2 and 12-3). Because dissemination to the peripheral blood indicates poor prognosis, the TNM staging is supplemented by hematologic staging (B0, B1, or B2). Peripheral blood involvement can be seen in 9% to 36% of early stage and up to 90% of late stage disease.38,39 Draining lymph nodes are the most common sites for extracutaneous involvement.
TABLE 12-2 MF and Sézary Syndrome TNMB Classification | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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TABLE 12-3 MF and Sézary Syndrome Staging | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Early patch/plaque stages (IIa) lack clonal lymph node involvement, whereas clonal T-cells are detected in ∼80% of tumor and erythrodermic MF cases using γ/δ or α/β TCR PCR.40,41,42 In some cases, lymph node involvement by MF is histologically apparent with effacement or distortion of the normal architecture by atypical cerebriform cells. In many instances, however, lymph node involvement by MF can be morphologically indistinguishable from dermatopathic lymphadenopathy (DL), a reactive lymph node enlargement that occurs at sites of either benign dermatoses or MF.43 In DL, lymph nodes show widening of the paracortex by proliferation of lymphocytes, immunoblasts, S100+ interdigitating dendritic cells, CD1a+ Langerhans’ cells, and melanin-laden macrophages. Clinically enlarged lymph nodes that lack histologically identifiable neoplastic T-cells but show features of DL are defined as stage N1 and Grade 1 by the ISCL/EORTC and Dutch classifications, respectively.44 Supplementation of lymph node staging with TCR-PCR-based molecular testing might predict poorer outcome.41,44
Lungs, liver, and spleen are the most common sites of visceral involvement (M1). Rare cases involving oral mucosa, nasopharynx, orbital tissue, small bowel, and central nervous system have also been reported.45,46,47,48 Bone marrow involvement can occur in advanced stages and is associated with a worse outcome.49
Association With Other Lymphoproliferative Diseases
Contemporaneous association of MF with other hematologic neoplasms is well documented, and numerous factors have been proposed to address the phenomenon. Immune dysregulation, therapy-related immunosuppression, and chemotherapy-induced secondary neoplastic transformation are only a few of the proposed mechanisms, although a shared biologic/genetic relationship between MF and the secondary malignancies cannot be entirely excluded. The temporal relationship between MF and secondary malignancies varies, but could be synchronous, preceding or following the initial presentation of MF. Approximately 25% of MF cases have associated lymphomatoid papulosis.50 Association with other CD30+ lymphoproliferative disorders, including anaplastic large cell lymphoma and Hodgkin disease as well as various forms of T-cell lymphomas, low-grade B-cell lymphomas (i.e., CLL), and diffuse large B-cell lymphomas, has also been observed.51
IMMUNOPHENOTYPE
In the majority of classic MF cases, neoplastic T-cells exhibit a CD3+βF1+CD4+CD8− mature T-cell phenotype (Fig. 12-13A–D). CD4−CD8+, CD4−CD8−, and CD4+CD8+ phenotypes have also been described, although less frequently.52,53,54,55,56 These variants appear to have similar clinical outcomes.57 Rare cases of classic MF with γ/δ phenotype have also been reported.58,59,60
 FIGURE 12-13. Classic immunophenotype of MF. A. CD3, B. CD4, C. CD8, and D. CD7. |
In patch stage disease, neoplastic cells preserve the expression of pan T-cell antigens, including CD2, CD3, and CD5, but they frequently lack CD7. The absence of CD7 expression is believed to be a result of neoplastic downregulation of CD7 expression, although some authors argue that MF cells derive from the transformation of a preexisting CD7− mature T-cell subset.61 In the later tumor stage, partial or complete loss of CD2, CD3, and CD5 has been observed.62
Establishing an elevated CD4:CD8 ratio, a sign of clonality, is regarded as the gold standard in the diagnosis of MF. It is best assessed by the comparison of CD8 versus CD3 and not CD4 versus CD8 stained tissue sections as dermal histiocytes and epidermal Langerhans cells express CD4, which can falsely elevate the number of CD4 expressing neoplastic T-cells.63 Evaluation of immunophenotypic skewing should be performed on epidermal T-cells as dermal infiltrates often harbor disproportionally elevated CD8 cytotoxic lymphocytes, unmasking the presence of neoplastic CD4+ cells in the early patch stage.64
Progression of MF is accompanied by a switch from TH1 and TH2 cytokine expression: epidermal TH1 cytokine profiles characterize patch and plaque stages, whereas TH2 cytokine profiles dominate tumor stages.65,66 Earlier works argued that TH1 predominance in patch stage MF is due to the predominance of antitumoral CD8+ lymphocytes, which is followed by the outgrowth of neoplastic TH2-skewed cells in the plaque and tumor stages.18 A recent study has found that it is the neoplastic T-cells that undergo a TH1–TH2 effector function switch during disease progression.22 Early patch stage MF cells express the TH1-specific T-bet but not the TH2-specific GATA-3 transcription factor. In plaques, neoplastic cells exhibit a mixed T-bet: GATA-3-expression pattern. As tumors evolve, neoplastic cells become diffusely GATA-3+ with minimal T-bet expression (Fig. 12-14A–I). T-bet and GATA-3 immunohistochemistry might be helpful in differentiating MF from its benign and malignant mimics.22
 FIGURE 12-14. Immune effector phenotypes in MF progression. A-C. Patch: TH1>>TH2, D-F. plaque: TH1∼TH2, G-I. tumor: TH2>>TH1. |
CD30 (Ki-1 antigen) is expressed by Reed Sternberg cells of Hodgkin lymphoma, by cells of anaplastic large cell lymphoma or lymphomatoid papulosis, and by immunoblasts in certain pseudolymphomas. Additionally, CD30 expression has been observed in a subset of patch stage and tumor stage MF with large cell transformation (Fig. 12-15).35,36,37,67 Although CD30 expression correlates with better disease-specific survival in large cell–transformed MF patients, no prognostic significance for CD30 expression was found in patch stage disease.68,69 Furthermore, therapeutic decisions are also affected by CD30 expression. Tumors with at least 10% CD30 expression are efficiently eradicated by CD30-targeted monoclonal antibody-immunotoxin therapy (brentuximab vedotin).70
 FIGURE 12-15. CD30 expression by large cell transformed MF. |
CD25 encodes the low affinity receptor for interleukin 2. Similar to CD30, its expression is more common in lesions from advanced MF patients.71 Although CD25 expression is often associated with Foxp3+ regulatory T (Treg) cells, and reactive Foxp3+ cells can be detected in both patch and tumor stage MF, the prognostic significance of the Treg phenotype in disease progression is not fully understood.72,73
CD56 (neural cell adhesion molecule or NCAM), an NK cell marker, is very rarely expressed in MF with CD4+, CD8+, or CD4−CD8− phenotypes.74,75,76 Distinction from CD56+ aggressive lymphomas including primary cutaneous NK/T-cell lymphoma, nasal type and blastic plasmacytoid dendritic cell neoplasm is paramount and requires clinical and histopathologic correlation.
Granzyme B (GrB), perforin, and T-cell-restricted intracellular antigen (TIA-1) are cytotoxic granule–associated proteins that are specifically expressed by cytotoxic CD4+ or CD8+ T-cells with either α/β or γ/δ phenotypes. They are only rarely expressed in early patch stage, but their expression increases in advanced disease.77
Expression of follicular helper T-cell (TFH) markers, PD-1, ICOS-1, CXCL-13 CD10, and BCL-6, has also been described in MF (Fig. 12-16).78,79,80,81 The biologic significance of these findings is still unclear, although some authors suggest that increased expression of PD-1 and its ligand PDL-1 in tumor stage MF may be co-opted by neoplastic cells to evade antitumoral immune response.79 Cases of MF with expression of follicular helper T-cell (TFH) markers have been associated with enriched B-cell infiltrates. More recently, Theurich et al.82 have shown that the clinical course of MF with abundant intralesional B-cells is more aggressive, and thus might be amenable to anti-CD20 therapy. The same therapy could also be exploited for rare cases of CD20+ MF (Fig. 12-17).83,84
 FIGURE 12-16. TFH marker expression by MF. A. Band-like epidermotropic infiltrates of atypical lymphocytes; B. expression of PD-1; C. ICOS; and D. CXCL-13. (Obtained with permission from Bosisio FM, Cerroni L. Expression of T-follicular helper markers in sequential biopsies of progressive mycosis fungoides and other primary cutaneous T-cell lymphomas. Am J Dermatopathol. 2015;37(2):115-121.) |
 FIGURE 12-17. CD20 expression by rare cases of MF. A and B. Rust-like staining with CD3 (red, chromagen) and CD20 (brown, diaminobenzidene) indicates colocalization of CD20 expression by CD3+ T-cells. (Obtained with permission from Hagen JW, Schaefer JT, Magro CM. CD20+ mycosis fungoides: a report of three cases and review of the literature. Am J Dermatopathol. 2013;35(8):833-841.) |
GENETIC AND MOLECULAR FINDING
Clonal rearrangement of the T-cell receptor locus can be detected in most cases, depending on the number of neoplastic cells and the molecular technique applied. Detection of monoclonality is, however, not pathognomonic to malignancy as persistent cutaneous inflammatory infiltrates of monoclonal or oligoclonal T-cells have been documented (Table 12-4). These clonal dermatitides (abortive/latent lymphomas) include conditions secondary to autoimmune or iatrogenic immune dysregulation (i.e., lupus profundus, lymphomatoid drug eruptions), pityriasis lichenoides et variolioformis acuta (PLEVA), actinic reticuloid, lichen planus, as well as chronic idiopathic dermatoses with persistent T-cell clones that are referred to as cutaneous T-cell lymphoid dyscrasia.88 Although clonal dermatitides are thought to be biologically distinct from MF, 20% to 25% of these entities can progress to lymphoma within 5 years.31,85
TABLE 12-4 Histological Spectrum of Clonal Dermatitides (Abortive/Latent Lymphoma) | ||||||||||||||||||||||||||||||||||||
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