Primary cutaneous marginal zone lymphoma C85.1

Author: Prof. Dr. med. Peter Altmeyer

All authors of this article

Last updated on: 31.03.2021

Dieser Artikel auf Deutsch

Synonym(s)

Cutaneous marginal zone lymphoma; Extranodal marginal zone lymphoma; immunocytic malignant lymphoma; Immunocytoma; Immunocytoma of the skin; Lymphoma cutaneous B-cell lymphoma low malignant extranodal MALT-type lymphoma; Lymphoma cutaneous B-cell lymphoma monocytoides; Marginal zone lymphoma; Marginal zone lymphoma cutaneous; Marginal zone lymphoma of the skin; MLZ; PCMLZ; primary cutaneous immunocytoma; SALT

Definition
This section has been translated automatically.

Rare, indolent (low-malignant) primary cutaneous non-Hodgkin's B-cell lymphoma (NHL) consisting of small B-cells, centrocytic cells (marginal zone cells), plasma cells and lymphoplasmocytoid cells. This group of B-cell lymphomas belongs to the extranodal marginal zone lymphomas (MALT). It includes lymphomas previously described as "primary cutaneous immunocytomas" or "cutaneous follicular lymphoid hyperplasia with monotypic plasma cells". The rare cases of (extramedullary) primarily cutaneous plasmocytomas or M. Waldenström also belong to this group. Primary cutaneous marginal cell lymphoma (SALT = skin associated lymphoid tissue) is considered an extranodular variant of MLZ lymphomas.

Occurrence/Epidemiology
This section has been translated automatically.

Men are affected slightly more often than women.

Etiopathogenesis
This section has been translated automatically.

MLZ develops from transformed cells of the so-called marginal zone of the lymph node. Due to its proliferation ability in non-lymphatic tissue (including skin (SALT-S for skin and associated lymphoid tissue), the MLZ is the mucosa(MALT-M for mucosa) and bronchus (BALT-B for bronchus). The cells express on their surface markers expressed by mature B cells (they react positively for IgM and/or IgD, CD5, CD19, CD20, CD22, CD24, CD45 and CD79A).

Furthermore, they usually express the surface antigens CD5 and CD43, but not CD10 and CD23.

The genetic "fingerprint" is a translocation t(11;14)(q13;q32). The translocation leads to a repositioning of the cyclin D1 gene (11q13) near strong transcriptional enhancer sequences of the immunoglobulin gene coding for the heavy chains (IgH) (14q32). It is assumed that the translocation occurs during recombination of the D and J heavy chain gene segment in pre-B cells. Since this translocation is a major feature of mantle cell lymphoma, its detection by FISH (= fluorescence in situ hybridization) is used for diagnostic purposes. This genomic alteration leads to an overexpression of cyclin D1.

In addition to the translocation t(11;14)(q13;q32), other recurring genomic changes occur in mantle cell lymphoma. Genomic gains often occur on the long arms of chromosomes 3 and 18; genomic losses are found on the short arms of chromosomes 1 and 9 as well as on the long arms of chromosomes 9, 6 and 11. The target genes affected by these genomic changes mainly influence the regulation of the cell cycle, DNA repair and apoptosis.

Infections: To what extent an infection with Borrelia burgdorferi is etiologically significant for the primarily cutaneous MLZ remains hypothetical. For the MALT a connection with a chronic infection with Helicobacter is likely. For the marginal zone lymphoma of the eye a possible association with Chlamydia-psittaci is secured.

Somatic mutations: SALT has characteristics of so-called aberrant somatic hypermutation. These concern genes such as PAX5 (paired box 5), the transcription factor cMYC and the protooncogene PIM1. Its cytogenetic feature is the chromosomal translocation of t(14;18).(q32;q21).

Manifestation
This section has been translated automatically.

In the group of extranodular MLZ in larger collectives, the average age of initial manifestation is 35-60 years.

Localization
This section has been translated automatically.

In the reported cases, the lower extremity predominates, followed by the trunk and face.

Clinical features
This section has been translated automatically.

Mostly disseminated, less frequently solitary, indolent, red or reddish-brownish papules, plaques and nodules with smooth, non-scaly surface. Ulcer formation is rare. Spontaneous regression of the lesions is possible. An association with Borrelia burgdorferi infections is described in European populations, but not in Asian or American populations.

Imaging techniques are necessary to distinguish primary cutaneous marginal zone lymphoma from systemic (nodal, splenic, gastric) marginal zone lymphoma with cutaneous involvement (CT: neck, thorax, abdomen/pelvis); sonography lymph nodes.

Laboratory
This section has been translated automatically.

Serum electrophoresis is recommended in addition to the routine laboratory with differential blood count. Borrelia and Chlamydia serology. A bone marrow biopsy is optional (in 5-10% focal infiltrates are expected).

Histology
This section has been translated automatically.

Nodular or diffuse infiltrates in the area of the entire dermis. The epidermis remains free of infiltrates. The histopathological pattern shows reactive germinal centres surrounded by neoplastic marginal zone cells (centrocyte-like cells), lymphoplasmocytoid cells and plasma cells. Small to medium-sized cells with notched nuclei and a pale, broad cytoplasm predominate. Occasionally also centroblasts, immunoblasts and some eosinophils. Rarely is a transformation into a large cell B-cell lymphoma.

Immunohistology (see CD-classification): Tumor cells show positivity for CD20, CD79a and BCl2 and, in contrast to primary cutaneous germinal tumors, negativity for BCL6. Monoclonal immunoglobulin expression with expression of the heavy chains of IgG and IgA (but not IgM) could be detected in the majority of cutaneous cases. One of the two light chains kappa or lambda are expressed predominantly. A ratio of 5:1 to 10:1 is considered diagnostically conclusive. Typically, the monoclonal cells are located at the periphery of the nodular infiltrates.

Note: The actual tumor portion in the total infiltrate is often small, since numerous reactive inflammatory cells (especially reactive T cells) are added to the infiltrate. In some cases this makes it difficult to differentiate it from a pseudolymphoma.

Differential diagnosis
This section has been translated automatically.

Therapy
This section has been translated automatically.

The therapy suggestions are based on the S2K guideline- Cutaneous Lymphoma, Update 2016.

Solitary lesion: Patients with solitary or few lesions can be treated either surgically and/or with involved field irradiation. The radiation dose ranges from 20-36Gy. The rate of full remissions is comparably high in both procedures, >95%.

Multiple lesions: In patients with multiple lesions, good results were obtained with systemically or intralesionally applied anti-CD20-Ak ( rituximab). Alternative anti-CD-20 antibodies such as Ofatunumab and Obinutuzumab have been proven in individual cases (Nicolay 2016).

Associated Borrelia infection: Patients with an associated Borrelia infection (see case report) should first be treated with antibiotics (multiple cycles over 21 days with Ceftriaxone 2 g i.v./day).

Alternatively, (experimental) studies with intralesional low-dose interferon alfa-2a therapy (3 times/week) or intralesinal application of the anti-CD20 antibody(rituximab) showed clear clinical success up to complete remission. However, they are clearly to be regarded as therapy of the 2nd choice.

Alternative: Bendamustin, possibly in combination with rituximab (S2k guideline)

Alternative: Doxorubicin or Gemcitabine, possibly in combination with Rituximab

As last resort, chemotherapy with doxorubicin or gemcitabine is recommended for multiple nodes.

Progression/forecast
This section has been translated automatically.

Excellent prognosis with a 5-year survival rate of almost 100% (Wilcox 2015). The prognosis is also not impaired by repeated cutaneous recurrences.

Note(s)
This section has been translated automatically.

Under the term MLZ the older designations, some of which are still in use, are subsumed:

Case report(s)
This section has been translated automatically.

  • An 84-year-old female patient in good DC and AZ presented with several months old livid-red, partially eroded, otherwise surface smooth nodules and plaques on the right forearm. There was a clear, inguinal, painless lymphadenopathy.
  • Laboratory: low thrombocytopenia; protein electrophoresis: detection of a monoclonal IgG band. Infections with EBV, CMV, Coxsackie Virus, Toxoplasma gondii and Helicobacter pylori could be excluded. Detection of a positive Borrelia IgG AK.
  • The somatic examination showed no evidence of organ involvement.
  • Histology: Dense infiltrates of CD20 positive lymphocytes; monoclonal k-light chain restriction. PCR analysis: detection of Borrelia burgdorferi DNA. By means of sequence analysis of the amplified DNA, Borrelia afzelii could be identified as the underlying genospecies.
  • Diagnosis: B. afzelii-induced cutaneous marginal zone lymphoma
  • Therapy: Under an antibiotic therapy with Ceftriaxon 2g i.v. for 3 weeks there was a clear regression of the nodules.

Literature
This section has been translated automatically.

  1. Akhtari M et al (2015) Primary Cutaneous B-cell Lymphoma (Non-Leg Type) Has Excellent Outcomes Even After Very Low Dose Radiation as Single-Modality Therapy. Leuk Lymphoma 10:1-13
  2. Cerroni L, Kerl H (2003) Cutaneous B-cell lymphoma. In: H. Kerl et al (eds) Histopathology of the skin. Springer Berlin, Heidelberg, New York, pp. 906-908.
  3. Cozzio A et al. (2006) Intra-lesional low-dose interferon alpha2a therapy for primary cutaneous marginal zone B-cell lymphoma. Leuk Lymphoma 47:865-869
  4. Defrancesco I et al (2017) Overview on the management of non-gastric MALT lymphomas. Best Pract Res Clin Haematol 31:57-64.
  5. Fühler M et al (2010) Cutaneous marginal zone lymphoma (SALT) in chronic Borrelia burgdorferi infection. Dermatologist 61:145-147
  6. Kim MJ et al. (2015) Clinical features and treatment outcomes of primary cutaneous B-cell lymphoma: a single-center analysis in South Korea. Int J Hematol. 2015: 101: 273-278
  7. Kiyohara T (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. Nicolay JP (2016) B-cell lymphomas of the skin - pathogenesis, diagnosis and therapy. J Dtsch Dermatol Ges 14:1207-1225.
  10. Servitje O (2002) Primary cutaneous marginal zone B-cell lymphoma: a clinical, histopathological, immunophenotypic and molecular genetic study of 22 cases. Br J Dermatol 147: 1147-115
  11. Soda R et al (2001) Systemic therapy of primary cutaneous B-cell-lymphoma, marginal zone type, with rituximab, a chimeric anti-CD20-monoclonal antibody. Acta Derm Venereol 81: 2007-2008
  12. Taddesse-Heath L (2003) Marginal zone B-cell lymphoma in children and young adults. Am J Surg Pathol 27: 522-531
  13. Teckie S (2015) Long-term outcome and patterns of relapse of early-stage extranodal marginal zone lymphoma treated with radiation therapy with curative intent. Int J Radiat Oncol Biol Phys 92: 130-137
  14. Wehkamp U et al (2015) Skin involvement of mantle cell lymphoma may mimic primary cutaneous diffuse large B-cell lymphoma, leg type. Am J Surg Pathol 39:1093-1101
  15. Wenzel C (2003) Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue of the head and neck area: high rate of disease recurrence following local therapy. Cancer 97: 2236-224
  16. Wilcox RA (2015) Cutaneous B-cell lymphomas: 2015 update on diagnosis,
  17. risk-stratification, and management. Am J Hematol 90:73-76
  18. Wobser M et al (2013) E. Primary cutaneous marginal zone lymphoma with sequential development of nodalmarginal zone lymphoma in a patient with selective immunoglobulin A deficiency. J Cutan Pathol 40:1035-1041
  19. Wutte N et al (2011) B. afzelii - induced cutaneous marginal zone lymphoma - A European entity? Abstract CD 46th DDG Conference.

Outgoing links (27)

Bcl2; Bcl6; Cd10; Cd19; Cd20; Cd22; Cd23; Cd24; Cd43; Cd45; ... Show all

Disclaimer

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

Authors

Last updated on: 31.03.2021