Diagnosis of MF is challenging; with the lack of a diagnostic gold standard and the many benign conditions, MF can mimic in its early stages. Diagnosis requires correlation between the clinical presentation along with histopathologic and immunophenotypic findings of the skin biopsy, including seeking to identify a clonal T-cell population clustered at the basement membrane of the epidermis. The malignant clone should bear the immunophenotype of activated, skin-homing CD4+ helper T cells that interact with antigen-presenting dendritic (Langerhans) cells in the epidermis [4]. A typical immunophenotype is CD2+, CD3+, CD4+, CD45RO+, CLA+, and CD8− (cytotoxic T cell) [5].

Early MF typically presents in patch phase, eventually progressing to plaques, tumors, and erythroderma (>80 % body surface involvement with confluent patches/plaques) (Fig. 12.2). With progression, there is loss of epidermotropism, lymphoid infiltration increasing in density and invasion into the deeper reticular dermis, and ultimately the development of tumor. The Pautrier’s microabscess is considered pathognomonic but occurs in less than 20 % of early lesions. The World Health Organization- European Organization for Research and Treatment of Cancer (WHO-EORTC) established the pathologic classification scheme for CTCL including MF [6–8]. Variants include folliculotropic and granulomatous slack skin MF.

A thorough history should demonstrate attention to duration, change, and distribution of lesion(s) and an understanding of symptoms including pruritis, pain, exfoliation, fissures, bullae, and perineal/perianal discomfort or evidence of involvement. The skin examination is critical not only for RT planning but also for staging and characterization of the percent cutaneous involvement by BSA and mSWAT scores. Skin photographs are important for documentation and anticipation of the chronic waxing and waning of disease over time and treatment. Adenopathy and organomegaly should also be documented. After biopsy, complete staging evaluation for this patient included complete blood count (CBC) with differential, comprehensive metabolic panel (CMP), serum chemistries (including renal and hepatic function), and lactate dehydrogenase (LDH), all of which were normal for this patient. Concerning lymph nodes, particularly those ≥1.5 cm, may require excisional biopsy. PET/CT scan and bone marrow biopsy are not required in patients presenting with early stage, limited disease, but should be considered in patients with a higher burden of skin involvement or other concerning findings such as clinical abnormalities or large-cell transformation on pathology. Peripheral blood flow cytometry is typically performed to assess expression of CD2, CD3, CD4, CD5, CD7, CD8, CD20, and CD45RO.

Current staging is based on the TNMB system, as proposed by the European Organization for Research and Treatment of Cancer (EORTC)/International Society for Cutaneous Lymphomas (ISCL). This staging includes MF and Sézary syndrome (SS) and considers skin, nodal involvement, and clonal and tumor burden in the blood [9]. T stage consistently demonstrates strong prognostic significance. Patients with limited patch and plaque involvement (stage IA, T1 N0 M0) demonstrate 10-year survival comparable to matched controls, while a dose response in the survival curve is demonstrated in patients with extensive patches and plaques (T2), tumors (T3), and erythroderma (T4), with median 11-, 3.2-, and 4.6-year survival, respectively [10]. In contrast, the independent prognostic significance of nodal involvement on overall survival is less clear, though overall stage is still correlated with outcome [11]. Other prognostic factors previously identified in studies include older age, large-cell transformation, elevated LDH [12], increased soluble interleukin-2 receptor levels [13], lower percentage of CD8⁺ tumor-infiltrating lymphocytes [14], or T-cell clonality within the cutaneous infiltrate, blood, and/or nodes [15–18].

For the patient’s stage IA MF, a definitive radiation treatment approach was offered. The radiation treatment plan targeted the visible sole plaque of the skin of the chin plus a margin for penumbra and setup error (1.5 cm beyond all visible and palpable abnormality), using local appositional electrons to a total dose of 20 Gy in 10 fractions. With the consideration of decreasing toxicity to normal tissue and with the understanding that repeated courses of radiotherapy might be likely in the future, the lowest possible electron energy directed at only the involved site was chosen. Appositional 9 MeV electron treatment was adequate to cover the thickness of the lesion. Cotton rolls were placed between the lip and the gingiva to decrease the electron backscatter, avoiding excessive toxicity to the mucosa (see Fig. 12.3 ). Patients will often have undergone a CT scan during their workup, and this imaging can be helpful to determine the thickness of the lesion to inform electron energy. Otherwise, for nodules or irregular skin surfaces, CT simulation may be helpful for choosing the electron energy that ensures adequate depth.

Presentation of MF with a single cutaneous lesion is rare, with most early stage patients, though presenting with limited skin surface area involvement, still having multiple lesions. The treatment strategy for MF depends on whether it is early vs. advanced or refractory in presentation [19]. For early disease, first-line treatment strategy is based on sequential skin-directed therapies, including RT, with the goal of providing the most durable response, with the least toxicity. As the disease becomes increasingly refractory, systemic, targeted, or combined therapies are second-line considerations, though RT remains an option.

For patients with disease limited to the skin, the skin-directed therapies including corticosteroids, mechlorethamine (nitrogen mustard), carmustine (BCNU), bexarotene gel (rexinoids), psoralen plus ultraviolet A (PUVA), ultraviolet B (UVB), and either localized or total skin electron radiotherapy all render high rates of control, particularly in patients presenting with localized uni-lesional MF or <10 % BSA involvement [20–22]. Long-term disease-free survival still ranges from 30 to 50 % in prior studies of these patients. Patients with more extensive cutaneous involvement still typically achieve initial control with these therapies, but long-term cure is unlikely [23, 24].

Radiation remains a highly effective treatment for MF, though determining the optimal dose is challenging [25]. The dose response with RT was well documented both for local RT and total skin electron beam therapy (TSEBT), and as a result, historically, RT doses >30 Gy were considered standard. More recently, the high rates of effective cutaneous control for lower doses has been increasingly appreciated, as high as 88 % overall response rate in a series of patients treated with 12 Gy TSEBT with mild and reversible toxicities [26, 27]. Accordingly, there is increasing consensus that the incremental local control benefit of higher RT doses may not outweigh the concomitant incremental toxicity—with a consequent shift toward low-dose RT as a standard approach. The International Lymphoma Radiation Oncology Group (ILROG) consensus field and dose guidelines consider local RT doses ranging from 6 Gy to >30 Gy as acceptable, with an emphasis on recommending lower doses for palliation and doses from 20 to 24 Gy for uni-lesional MF. The recommended target for treatment is the lesion plus 1.0–2.0 cm margin for local palliation and the entire skin for TSEBT, using electron technique (customarily 6–9 MeV with bolus for patch, and higher energies for thicker plaques or tumors and exophytic lesions) [28].

The early stage MF patient developed mild erythema and dry skin with RT, completely resolved at 4–week follow–up. At the last follow–up, 20 months after treatment, the lesion remained in complete remission (Fig. 12.4 ). Unfortunately, the patient developed another similar small lesion on the left arm, which was biopsy-proven MF. This lesion is currently well controlled with topical corticosteroids only. Typical follow–up visits every 3–6 months include a history and physical examination including comprehensive skin examination, blood work (including a CBC and LDH), swab and culture of any lesions concerning for infection/colonization, and repeat imaging only as needed.

A healthy 52-year–old female hairdresser noted an itchy lesion over the left ear. She managed it for months using topical steroids. However, the lesion kept growing, eventually forming a tumor (see Fig. 12.5 ). After 18 months, biopsy confirmed MF. Careful skin examination showed another lesion in close proximity on the left ear, as well as one on the back of the neck measuring 1.5 × 2 cm. Staging workup showed no evidence of disease in the marrow, nodes, or internally. The patient was referred to receive definitive radiation therapy. The patient was simulated with an open neck position, with the area to be targeted clinically traced with radioopaque wires. The treatment was planned using a single appositional electron field with 6 MeV electrons, and in an effort to avoid the parotid gland, skin collimation was applied (see Fig. 12.6 ). To overcome the irregularity of the skin, a tissue-equivalent material was used to compensate for the gaps and form a uniform surface. A 1 cm tissue-equivalent bolus was placed over the lesion to ensure that 100 % of the dose would reach the surface (see Fig. 12.7 ). A total dose of 12 Gy in six treatments was delivered. The patient was discharged with moisturizers to apply to the treated area. A picture of the lesion was taken almost on a weekly basis until complete disappearance of the lesion on week 12 (see Fig. 12.8 ).

The patient did well for a year before she presented with another lesion over the face that was again treated with radiation. Today almost 18 months after treating her ear, the later site is still well controlled. This case is a good example of how lowering the dose can still offer a durable local control.

A key caution is to allow lesions to heal, even if healing appears slow, sometimes taking several months. As long as a continuous improvement is seen, we recommend continued observation. Patients not infrequently demonstrate a natural history consisting of local lesions only that respond very well to either topical treatment or low-dose radiation. Especially for such patients, the treatment strategy should avoid unnecessary radiation to surrounding critical organs, for instance in this case the parotid gland.