Cutaneous b-cell lymphomas (overview) C82- C83

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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Synonym(s)

B-cell lymphomas of the skin; CBCL; Cutaneous B-cell lymphoma; cutaneous B-cell lymphomas; Cutaneous BCL; Cutaneous lymphomas B-cell lymphomas; primary cutaneous; Primary cutaneous B-cell lymphoma; Primary cutaneous B-cell lymphomas

Definition
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Primary cutaneous B-cell lymphomas are neoplasias of the lymphatic system, which show a tissue-specific "homing pattern" with primary infiltration and manifestation in the skin. They exhibit a characteristic B-cell phenotype.

Clinically, cutaneous B-cell lymphomas present as solitary or multiple, low symptom, red or red-livid or red-brown, surface-smooth papules, plaques or nodules. The classification is based on histological criteria according to the WHO-EORTC classification of non-Hodgkin lymphomas.

For therapy and prognosis it is crucial whether the disease is a primary cutaneous B-cell lymphoma or a secondary skin infection in case of nodal B-cell lymphoma!

The 3 most frequent subtypes are (see classification):

Classification
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CBCLs can be classified as low or intermediate malignancy according to their degree of malignancy. It is also important whether it is a primary (lymphoma of the skin as the sole manifestation of the disease) or secondary (lymphoma of the skin as a secondary infestation following extracutaneous manifestation of the disease) cutaneous B-cell lymphoma. Among the B-cell lymphomas in which the skin is usually only involved secondarily (metastatically) is mantle cell lymphoma (MZL), a diffuse centrocytic, non-follicular "germinal centre lymphoma".

Depending on the dignity of the primary cutaneous B-cell lymphomas can be distinguished as follows (032/027 S2k guideline cutaneous lymphomas):

According to histological/immunohistological criteria a distinction is made between:

Occurrence/Epidemiology
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The proportion of B-cell lymphomas in the skin is estimated at about 20-25% of primary cutaneous lymphomas. They are thus significantly less common than cutaneous T-cell lymphomas. The incidence is about 0.3 new cases/100,000 per year.

Clinical features
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In 2/3 of the cases primarily only skin infestation without extracutaneous manifestation. In advanced stages, systemic involvement of varying extent and localization.

Specific skin changes: Mostly asymptomatic red, red-livid or reddish-brown, surface-smooth, firm papules, plaques or nodules with mostly unchanged, rather reflective surface. In late stages ulcerations are possible. The clinical features of the different entities can be found under the respective keyword.

Non-specific skin changes: erythroderma, eczema, pigmented and infiltrated foci. Amyloid deposits in the skin: papules, nodules. Alopecia. Also macroglossia, cryoglobulinemia, disseminated plane xanthomas, zoster, epidermolysis bullosa acquisita, pruritus, symptomatic purpura, ichthyosis, lichenification.

General symptoms: Enlargement of lymph nodes, splenomegaly, involvement of lung, liver, also stomach and bone marrow.

Histology
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See below the respective entities.

Diagnosis
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The exact diagnosis and definitive allocation is based on the synopsis of clinical and histological parameters.

Differential diagnosis
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The cutaneous B-cell lymphomas appear rather uniform in their clinical presentation, characterized by solitary or multiple, localized or also disseminated, indolent, smooth (rarely ulcerated), red to brown-red, moderately firm papules and nodules. The differentiation between primary cutaneous genesis or secondary cutaneous infestation cannot be determined by the clinical picture alone, but only in the summary of all staging examinations.
  • Common clinical differential diagnoses:
    • Lymphadenosis cutis benigna (pseudolymphoma of the skin; main differential diagnosis): Large nodular solitary (most frequent appearance) or small nodular multiple (rare), circumscribed, symptomless, firm, red, brown to brown-red, hemispherical bulging nodules or papules covered by thin epithelium. Reliable differential diagnostic differentiation is only possible histologically!
    • Lymphoma, cutaneous T-cell lymphoma (important DD): Rather polymorphic appearance, ranging from eczematoid, ichthyosiform ( Mucinosis follicularis) or psoriasiform to erythrodermic ( Sézary syndrome) manifestations. Cutaneous T-cell lymphoma of the mycosis fungoides type can usually be ruled out on the basis of the anamnesis (parapsoriasis stage). A smooth surface structure of a lesion is also more likely to indicate a B-cell lymphoma.
    • Lupus erythematodes tumidus: Occurs at light-exposed sites; mostly disseminated plaques; pronounced photosensitivity.
    • Granuloma eosinophilicum faciei (rare; only to be considered for differential diagnosis in case of facial localisation): Roundish to oval, 0.5-2.0 cm in size, usually solitary, slightly raised, firm, symptom-free, brown-red, scale-free plaques with "orange peel-like" surface aspect. This is missing in cutaneous B-cell lymphomas.
    • Merkel cell carcinoma (to be considered as DD in solitary infestation and localization in UV-exposed areas): Occurs in the age group 60-70 LJ. Fast growing node; mostly solitary. The surface of the nodule is smooth, rarely crusty or ulcerated. At depth there is often an iceberg-shaped widening of the knot. Safe exclusion only possible by histology.
    • Dermatofibrosarcoma protuberans: Smooth, slowly growing node with iceberg phenomenon. Exceptionally rough consistency which is not present in lymphoma nodes.
    • Mastocytoma: Single or multiple plaques or nodes existing since birth or occurring in the first months of life (exclusion due to age of manifestation). After rubbing of the lesions urticarial or bullous reaction (positive foci urticarial or bullous reaction (positive rubbing test).
  • Rare clinical differential diagnoses:
    • Sarcoidosis: Especially the large-nodular form with brown- or blue-red, rough, plum-sized nodules and plaques, especially on the nose, cheeks and earlobes must be differentiated. Sarcoidosis often occurs in scars! Diascopic lupoid infiltrate. Histologically safe to differentiate!
    • Prurigo nodularis: Eminently chronic disease characterized by numerous, large, severely itchy nodules (B-cell lymphomas do not itch; pruritus is a symptom of exclusion).
    • Skin metastases: Nodular metastases are of differential diagnostic importance; usually fast-growing, rough (!) smooth, red nodules. Often iceberg phenomenon. Reliable exclusion is only possible by histology.
  • Extremely rare clinical differential diagnoses:
    • Cutaneous infiltrates in myeloid leukaemia: pinhead to hazelnut-sized, sharply defined, hard, blue to brown-red, sometimes blue-grey to livid-red, slightly necrotic nodules.
    • Reticulohistiocytosis, multicentre: Symmetrically distributed, multiple, 0.1-0.5 cm large, usually coarse, skin-coloured or copper-brown, sometimes slow-growing, sometimes eruptively exanthematic papules and nodules, possibly with atrophic, possibly excoriated, usually smooth surface. Itching is not uncommon.
    • Tuberous syphilide: Grouped standing, partly confluent, reddish-brownish, coarse to pea-size, calotte-shaped raised nodules, possibly scaling. Degeneration with development of a flat, hyper- or depigmented scar. Anamnesis and serology are diagnostic.
    • Cutaneous leiomyosarcoma: 2.0-5.0 cm large plaques or nodules, which can be moved against the underlying tissue, fused with the covering dermis, very firm, usually painful (!).

Therapy
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Due to the relative rarity of B-cell cutaneous lymphomas, there are no evaluated standard therapies.

  • Monoorganic cutaneous manifestation - few lesions:
    • Local therapy. Smaller foci can be surgically removed, larger foci are radiated: soft X-ray therapy (GD 20-30 Gy, in ED of 2 Gy, 50 kV each) or fast electron irradiation (GD 40 Gy).
  • Monoorganic cutaneous manifestation - multiple lesions:
    • Studies with excellent results in smaller cohorts exist on rituximab, an anti-CD20 antibody approved for cutaneous B-cell lymphomas. In the usual dosage (375 mg/m2 KO, 8 cycles) this preparation is indicated in elderly patients with disseminated, aggressive B-cell lymphoma. The mode of administration is also being discussed: intralesional treatments are well tolerated, show few side effects and use smaller amounts of medication. The clinical symptoms show significant improvements, but these do not last long. Recurrences occur frequently after intralesional therapy. Due to the small number of test persons, the data available for intravenous application are not meaningful at present.
  • Monoorganic cutaneous manifestation - multiple lesions (tumor progression):
    • In case of progression: polychemotherapy, if necessary in cooperation with haemato-oncologists, e.g. CHOP-scheme. Concerning the side effects see below. Common Toxicity Criteria (CTC).
    • Experimental: Electrochemotherapy has been used in individual cases in therapy-resistant lymphomas.

Progression/forecast
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Varies depending on the disease, cheap to serious.

Note(s)
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  • Mantle cell lymphoma typically shows the translocation t(11;14)(q13;q32) with an IgH-cycline D1 (CCND1) rearrangement. By this translocation, the BCL-1/cyclin D1/PRAD1 gene on chromosome 11 fuses with one of the 6 J regions of the immunoglobulin heavy chain (IgH) gene on chromosome 14 and thus comes under the control of the IgH enhancer (E).
  • In MALT lymphomas (extranodal marginal zone lymphoma mucosa-associated tissues) a translocation t(11;18)(q21;q21) is often observed. However, the genetic changes are very different, other IgH rearrangements or 6q deletions are also possible (see also FISH analysis).
  • In follicular lymphoma, a t(14;18)(q32;q21) with a BCL-2 rearrangement is found in the majority of cases; in addition, further cytogenetic aberrations are usually found.
  • Diffuse large cell B-cell lymphomas (DLBCL) often show rearrangements of BCL6, MYC or BCL2. However, they do not show specificity for a certain entity, but may also occur in other lymphatic entities.
  • In lymphoplasmocytic lymphoma no specific chromosomal aberrations are found.

Literature
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  1. Felcht M edt al (2011) Diagnosis of primary cutaneous B-cell lymphomas. Act Dermatol 37: 199-204
  2. Garbea A et al (2002) Cutaneous large B-cell lymphoma of the leg masquerading as a chronic venous ulcer. Br J Dermatol 146: 144-147
  3. Gellrich S et al (2005) Systemic eight-cycle anti-CD-20 monoclonal antibody (rituximab) therapy in primary cutaneous B-cell lymphomas - an application observation. Br J Dermatol 153: 167-173
  4. Hallermann C et al (2011) Malignant lymphomas of the skin. dermatologist 62: 947-958
  5. Hallermann C et al (2011) Survival data for 299 patients with primary cutaneous lymphomas: a monocentre study. Acta Derm Venereol. 2011 91:521-525
  6. Kerl K et al (2006) Intralesional and intravenous treatment of cutaneous B-cell lymphomas with the monoclonal anti-CD20 antibody rituximab: report and follow-up of eight cases. Br J Dermatol 155: 1197-1200
  7. Kiyohara T et al (2003) Cutaneous marginal zone B-cell lymphoma: a case accompanied by massive plasmacytoid cells. J Am Acad Dermatol 48: S82-85
  8. Li C et al (2003) Primary cutaneous marginal zone B-cell lymphoma: a molecular and clinicopathologic study of 24 Asian cases. Am J Surg Pathol 27: 1061-1069
  9. Mendes S, Dreno B (2003) Diagnosis of primary cutaneous B-cell lymphoma by immunohistochemical and in situ hybridization methods. Acta Derm Venereol 83: 167-170
  10. Nicolay JP et al (2016) B-cell lymphomas of the skin pathogenesis, diagnosis and therapy. JDDG 12: 1225
  11. Spugnini EP et al (2009) Electrochemotherapy for localized lymphoma: a preliminary study in companion animals. J Exp Clin Cancer Res 26: 343-346
  12. Storz MN et al (2003) Gene expression profiles of cutaneous B cell lymphoma. J Invest Dermatol 120: 865-870
  13. Willemze R et al (2005) WHO-EORTC classification for cutaneous lymphomas. Blood 105: 3768-3785

Disclaimer

Please ask your physician for a reliable diagnosis. This website is only meant as a reference.

Authors

Last updated on: 29.10.2020