B-cell lymphomas are a class of lymphoproliferative disorders that can originate in the lymph nodes, skin, or gastrointestinal tract. One form of non-Hodgkin B-cell lymphoma is primary cutaneous B-cell lymphoma (PCBCL), a rare subclass that originates in the skin.18
Though its incidence is on the rise, PCBCL is currently estimated to comprise 20% to 25% of all cutaneous lymphomas.19 PCBCL can be divided into 3 general subclasses: primary cutaneous follicle center lymphoma (CFCL), primary cutaneous marginal zone lymphoma (CMZL), and primary cutaneous diffuse large B-cell lymphoma of the leg (LBCL-L). In general, PCBCL occurs most frequently in white men and adults >50 years of age. CFCL and CMZL are often seen in middle-aged men, while LBCL-L is more often seen in elderly women.19
CFCL is the most common subtype of PCBCL.19 It grows slowly over months to years and is found as a nonpainful, nonpruritic solitary lesion or cluster of several nodular lesions on the head or trunk.19 CFCLs are slightly raised and smooth, appear pink or reddish, and usually do not ulcerate. CFCL is thought to arise from B cells in mature germinal centers.20 Almost all cases express B-cell markers CD19, CD20, and CD79a, and most cases express B-cell lymphoma (BCL)-6 but not BCL-2.20
CMZL is the second most common subtype of PCBCL. It is similar to MALT (mucosa-associated lymphoid tissue) lymphoma and also presents as pink or red papules, nodules, and/or tumors.16 CMZL is also slow-growing and can be found anywhere on the body.
LBCL-L is the least common, most aggressive subtype of PCBCL.19 These tumors most often appear on one or both of the lower legs of elderly women; however, 10% to 15% of these tumors involve sites other than the legs and, unlike other forms of PCBCL, extracutaneous dissemination is common.21 LBCL-L presents as red or bluish-red lesions that can grow quickly and ulcerate. LBCL-L often shows translocations in the MYC, BCL6, and IgH genes, and in contrast to CFCL, LBCL-L expresses BCL-2.16
When PCBCL is confined to the skin, the prognosis is very favorable, with an estimated 5-year survival rate of 95%.22 The exception is LBCL-L, which has a 5-year survival rate of approximately 70%.19 The rate of recurrence of PCBCL is approximately 50%; however, this disease rarely develops into a systemic lymphoma.22 There are no known risk factors or identifiable hereditary tendency for the development of PCBCL.
The differential diagnosis of PCBCL includes arthropod bites, basal cell carcinoma, and other cutaneous lymphomas. PCBCL should be suspected in a patient who presents with a suspicious skin lesion without signs of systemic lymphoma. A biopsy is required to evaluate the growth pattern, morphology, and immunohistochemistry of the lesion.21 Excisional biopsy is preferred to punch biopsy in most cases.21 Pathologic examination confirming PCBCL usually displays a B-cell infiltrate that spares the epidermis, with a follicular or diffuse pattern comprising centrocytes and centroblasts.21 Immunohistochemistry will display pan-B-cell markers (CD19, CD20, and CD79a).21,23
Inflammation with follicular hyperplasia that can occur in infection or arthropod bites may mimic PCBCL.24 The follicles in PCBCL, however, are more ill-defined and lack tingible body macrophages. Immunostaining for proliferation (Ki67) will show a smaller percentage of Ki67-positive cells in PCBCL than in infection, and PCBCL will demonstrate a homogeneous region of BCL-6-positive or BCL-2-positive B cells.24
Basal cell carcinoma (BCC) is a neoplasm that may mimic PCBCL. Both BCC and PCBCL may present as shiny, smooth, raised lesions on the head or trunk. On histopathologic examination, however, BCC will contain a mass of basophilic basaloid keratinocytes that have a connection to the epidermis.20 In contrast, PCBCL will contain follicles or sheets of B cells that exclude the epidermis. Additionally, on histology, BCCs may exhibit peripheral palisading, and this is not seen in PCBCL.
It is particularly important to distinguish PCBCL from systemic follicular lymphoma. Non-Hodgkin lymphomas can present in the skin either primarily or as a result of dissemination from systemic disease.25 On biopsy, the follicular centers of both tumors may resemble each other and will both stain for CD19, CD20, and BCL-6 or BCL-2 and will be negative for the T-cell markers CD5 or CD3.25 Clinically, patients with systemic lymphoma usually have fever, fatigue, and weight loss, while patients with PCBCL generally present without these symptoms.18 Additionally, the t(14;18) chromosomal translocation found in most systemic follicular lymphomas is not seen in PCBCL.25 T-cell lymphomas of the skin can be distinguished from PCBCL through the expression of T-cell markers CD5 and CD3.20
Because CFCL and CMZL are slow-growing, indolent lymphomas, they can often be treated with local radiation targeted to the lesion(s) or surgical excision.26 Topical or injected chemotherapy may also be used.26 Rituximab, a monoclonal anti-CD20 antibody, can be used in the management of extensive indolent PCBCL.26 Multi-agent chemotherapy, radiation, and rituximab in combination may be used in the treatment of LBCL-L.26 Patients with LBCL-L should also undergo positron emission tomographic (PET) imaging to evaluate for extracutaneous dissemination.
The patient in this case underwent biopsy, and pathologic examination revealed a dense, homogeneous follicle of lymphocytes confined to the dermis. Immunohistochemistry showed the presence of pan-B cell markers (CD19, CD20, and CD79a) and positive BCL-6 but negative BCL-2 staining. Fluorescence in situ hybridization for t(14;18) was negative. No extracutaneous disease was identified on PET imaging, confirming a diagnosis of CFCL. The patient underwent local radiation therapy, with complete remission of the disease.
Table. Basal Cell Carcinoma vs Cutaneous B-Cell Lymphoma
Cynthia Truong, BS, and Yelena Dokic, BSA, are medical students at Baylor College of Medicine, and Christopher Rizk, MD, is a certified dermatologist at Elite Dermatology in Houston, Texas.
- American Cancer Society. Cancer Facts & Figures 2016. American Cancer Society. 2016.
- Hannuksela-Svahn A, Pukkala E, Karvonen J. Basal cell skin carcinoma and other nonmelanoma skin cancers in Finland from 1956 through 1995. Arch Dermatol. 1999;135(7):781-786.
- Scotto J, Fears TR, Fraumeni JF. Incidence of Nonmelanoma Skin Cancer in the United States. National Institutes of Health; 1983. NIH publication 83-2433. Accessed 6/28/2020. http://www.ciesin.org/docs/001-526/001-526.html
- Gallagher RP, Hill GB, Bajdik CD, et al. Sunlight exposure, pigmentary factors, and risk of nonmelanocytic skin cancer. Arch Dermatol. 1995;131(2):157-163.
- Marcil I, Stern RS. Risk of developing a subsequent nonmelanoma skin cancer in patients with a history of nonmelanoma skin cancer: a critical review of the literature and meta-analysis. Arch Dermatol. 2000;136(12):1524-1530.
- Christenson LJ, Borrowman TA, Vachon CM, et al. Incidence of basal cell and squamous cell carcinomas in a population younger than 40 years. JAMA. 2005;294(6):681-690.
- Schreiber MM, Moon TE, Fox SH, Davidson J. The risk of developing subsequent nonmelanoma skin cancers. J Am Acad Dermatol. 1990;23(6 Pt 1):1114-1118.
- Marzuka AG, Book SE. Basal cell carcinoma: pathogenesis, epidemiology, clinical features, diagnosis, histopathology, and management. The Yale J Biol Med. 2015;88(2):167-179.
- Gailani MR, Ståhle-Bäckdahl M, Leffell DJ, et al. The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas. Nat Gen. 1996;14(1):78-81.
- Kim MY, Park HJ, Baek SC, Byun DG, Houh D. Mutations of the p53 and PTCH gene in basal cell carcinomas: UV mutation signature and strand bias. J Dermatol Sci. 2002;29(1):1-9.
- Rubin AI, Chen EH, Ratner D. Basal-cell carcinoma. N Engl J Med. 2005;353(21):2262-2269.
- McCormack CJ, Kelly JW, Dorevitch AP. Differences in age and body site distribution of the histological subtypes of basal cell carcinoma: a possible indicator of differing causes. Arch Dermatol. 2007;133(5):593-596.
- Sariya D, Ruth K, Adams-McDonnell R, et al. Clinicopathologic correlation of cutaneous metastases: experience from a cancer center. Arch Dermatol. 2007;143(5):613-620.
- Marks J, Miller J. Lookingbill and Marks’ Principles of Dermatology. 6th ed. Elsevier Health Sciences; 2018:42-44.
- Markowitz O, Utz S. Differentiating early stage cystic keratoacanthoma, nodular basal cell carcinoma, and excoriated acne vulgaris by clinical exam, dermoscopy, and optical coherence tomography: a report of 3 cases. J Clin Aesthet Dermatol. 2015;8(4):48-50.
- Willemze R, Kerl H, Sterry W, et al. EORTC classification for primary cutaneous lymphomas: a proposal from the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer. Blood. 1997;90(1):354-371.
- Neville JA, Welch E, Leffell DJ. Management of nonmelanoma skin cancer in 2007. Nat Clin Pract Oncol. 2007;4(8):462-469.
- Liu Q, Ohshima K, Kikuchi M. Primary cutaneous B‐cell lymphoma in Japanese patients. Pathol Int. 2000;50(12):960-966.
- Bradford PT, Devesa SS, Anderson WF, Toro JR. Cutaneous lymphoma incidence patterns in the United States: a population-based study of 3884 cases. Blood. 2009;113(21):5064-5073.
- Willemze R, Jaffe ES, Burg G, et al. WHO‐EORTC classification for cutaneous lymphomas. Blood. 2005;105(10):3768-3785.
- Senff NJ, Hoefnagel JJ, Jansen PM, et al. Reclassification of 300 primary cutaneous B‐cell lymphomas according to the new WHO‐EORTC classification for cutaneous lymphomas: comparison with previous classifications and identification of prognostic markers. J Clin Oncol. 2007;25(12):1581-1587.
- Akinyemi E, Mai L, Matin A, Maini A. Diffuse large B-cell lymphoma mimicking advanced basal cell carcinoma. J Natl Med Assoc. 2007;99(8):948-950.
- Swerdlow SH, Quintanilla-Martinez L, Willemze R, Kinney MC. Cutaneous B-cell lymphoproliferative disorders: report of the 2011 Society for Hematopathology/European Association for Haematopathology workshop. Am J Clin Pathol. 2013;139(4):515-535.
- Grange F, Beylot-Barry M, Courville P, et al. Primary cutaneous diffuse large B-cell lymphoma, leg type: clinicopathologic features and prognostic analysis in 60 cases. Arch Dermatol. 2007;143(9):1144-1150.
- Sterry W, Krüger GR, Steigleder GK. Skin involvement of malignant B‐cell lymphomas. J Dermatol Surg Oncol. 1984;10(4):276-277.
- Hamilton SN, Wai ES, Tan K, Alexander C, Gascoyne RD, Connors JM. Treatment and outcomes in patients with primary cutaneous B-cell lymphoma: the BC Cancer Agency experience. Int J Radiat Oncol Biol Phys. 2013;87(4):719-725.