Primary cutaneous lymphomas are a group of non-Hodgkin lymphomas that manifest themselves primarily in the skin without evidence of extra-cutaneous disease at the time of initial presentation. These malignant skin wounds represent clonal proliferation of neoplastic B cells or T cells that migrate from the blood to the skin and cause the progressive lesions. Secondary skin involvement of B-cell lymphomas can occur as a result of retrograde lymphatic spread from involved lymph nodes, hematogenous dissemination, and direct extension to the skin from the underlying lymph nodes. Diagnosis requires a thorough history and physical examination, tissue samples and analysis, laboratory studies, and imaging in order to properly diagnose and stage the lymphoma, as well as to direct medical care. The biopsy must be done with an incisional, excisional, or punch biopsy of the central tissue (not the peripheral periwound skin) for adequate sampling.
In 2005 the World Health Organization and European Organization for Research and Treatment of Cancer (WHO-EORTC) classified primary cutaneous lymphomas as either T-cell or B-cell with subdivisions of each type. The classification was revised in 2018 with the same two classifications plus variations in the subdivisions; the most common types are as follows:
- Cutaneous T-cell lymphoma
- Mycosis fungoides (MF) and its variants
- Sézary syndrome
- Primary cutaneous CD30+ T-cell lymphoproliferative disorders (LPD)
- Primary cutaneous CD4+ small/medium T-cell LPD
- Primary cutaneous peripheral T-cell lymphoma, NOS
- Chronic active Epstein Barr virus infection LPD
- Cutaneous B-cell lymphoma
- Primary cutaneous marginal zone lymphoma
- Primary cutaneous follicle center lymphoma
- Primary cutaneous large B-cell lymphoma, leg type
- Epstein Barr Virus+ mucocutaneous ulcer
- Intravascular large B-cell lymphoma
Each of the subtypes has a distinct histopathology, immunohistochemistry, molecular genetics, and clinical presentation which is beyond the scope of this discussion; however, some of the lesions can mimic wounds caused by venous disease, trauma, cysts, or other skin disorders. Therefore, any skin lesion that persists and does not respond to standard care in 2-3 weeks should be further evaluated with a tissue biopsy and imaging in order to diagnose, stage, treat, and make a prognosis. Because the infiltrate of the lesions may be affected by topical steroids or other topical or systemic immunosuppressive agents, the patients are advised to be off these medications for at least two weeks before the skin biopsy. Some of the more common clinical presentations include the following:
Mycosis fungoides – Classic type of T-cell lymphoma; presents initially with flat, scaly, itchy patches that progress to reddish, purplish, or brownish plaques which may in turn become raised nodules or open tumors. Usually occur on lower abdomen, upper thigh and groin, buttocks, breasts, armpits, or crook of the elbow, on individuals over 50 years old.
Folliculotropic mycosis fundoides – a variant that differs from the classic by the presence of folliculotropic infiltrates; may spare the epidermis; usually occurs on the head and neck region with grouped follicular papules, acneiform lesions, and associated alopecia. Is more aggressive than the classic type.3
Sézary syndrome – presents with the “triad of pruritic erythroderma, generalized lymphadenopathy, and clonally related neoplastic T cell with cerebriform nuclei in the skin, lymph nodes, and peripheral blood” (an important diagnostic finding)3
Primary cutaneous CD30+ T-cell lymphoproliferative disorders (LPD) – Clinical presentation may vary depending on the subtype, but all will have CD30+ T cells present on histological evaluation.3,4
Primary cutaneous CD4+ small/medium T-cell LPD – generally presents with a single plaque or tumor on the face, neck or upper trunk. May resolve spontaneously; if not, treated with intralesional steroids or surgical excision.3
Primary cutaneous marginal zone lymphoma – affects young adults; presents with single or multifocal plaques or nodules, usually on the trunk and arms.3
Primary cutaneous follicle center lymphoma – usually presents with localized lesions on the head or trunk; can be treated by local radiotherapy with excellent results.3
Primary cutaneous large B-cell lymphoma, leg type – generally affect older women; present with rapidly growing tumors on one or both legs; may disseminate to other sites; have less favorable prognosis.
Epstein Barr Virus+ mucocutaneous ulcer – presents as a single, sharply demarcated, ulcerative lesion on the skin, oropharyngeal mucosa, or gastrointestinal tract in patients who are older or immunosuppressed (e.g. methotrexate, azathioprine, cyclosporine, or tumor necrosis factor inhibitors)
All primary cutaneous lymphomas are confirmed with biopsy and staged according to the guidelines established by the International Society for Cutaneous Lymphomas, the US Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the EORTC.4 Treatment is individualized based on the diagnosis and should be directed by a qualified specialist. The primary provider of care is advised to refer any patient with a wound that does not respond to standard care in 2-3 weeks and has no other identifiable etiology, to a specialist for further assessment so that an accurate diagnosis can be made and treatment initiated as soon as possible in order to obtain the optimal outcome.
On a personal note, I chose this category of malignant wounds from an experience with a dear friend who asked me to see her non-healing wound on the anterior mid lower leg – too proximal to be the usual arterial or venous wound. She had been treated at a local wound care clinic for over a year with what I call the “clean, cut, and cover” approach to wound care. Visually I knew this was an atypical wound, possibly malignant, but knew I was not the one to make a diagnosis. I suggested she see a dermatologist or plastic surgeon, and she went to a plastic surgeon she knew from previous experiences. Fortunately, he was very astute and knowledgeable about primary cutaneous lymphoma, made an immediate diagnosis, and referred her to an oncologist for treatment. The complications from having this disease for that period of time resulted not only in unnecessary angst and discomfort for the patient that greatly affected her quality of life, they ultimately led to a below-knee amputation.
As I conclude this series of 52 posts on diagnosing and treating patients with wounds, the lesson which I would like to leave with all of you is to approach each patient with these two questions: Why does the patient have the wound? and Why is the wound not healing? Successful treatment depends upon answering both of these questions, and demands that we spend time with the patient and/or care-giver, that we “hear” all of their spoken and unspoken complaints and insights relative to their condition. Finally, we must care for these patients as a team, addressing the whole patient and not just the visible lesion. God bless you as care for His children.
More information on caring for patients with wounds may be found at the following site:
Hamm R (Ed), Text and Atlas of Wound Diagnosis and Treatment: 2nd edition. New York: McGraw Hill Education. 2019, 101-143. Available at https://accessphysiotherapy.mhmedical.com/book.aspx?bookid=1334.
 Dhadlie S, Strekozov B. Cutaneous extra nodal lymphoma relapse: A case report and review of literature. Int J Surg Case Reports. 2018;51:306-308.
 Malachowski SJ, Sun J, Chen P, Seminario-Vidal L. Diagnosis and management of cutaneous B-cell lymphomas. Dermatol Clin. 2019;37(4):443-454.
 Willemze R, Cerroni L, Kempf W, Berti E, Facchetti F, Swerdlow SH, Jaffe ES. The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas. Blood. 2019;133(4):1703-1714.
 Olsen E. Evaluation, diagnosis, and staging of cutaneous lymphoma. Dermatol Clin. 2015;33:643-654.
 Mycosis fungoides. Available at https://ghr.nlm.nih.gov/condition/mycosis-fungoides. Accessed July 5, 2020.