2.2.9 Lymphadenosis Cutis Benigna

Grading & Level of Importance: B

ICD-11

EE91 / 1C1G.14

Synonyms

Pseudolymphoma, Borrelia lymphocytoma, Spiegler-Fendt-Sarcoid, Lymphocytic infiltration, reactive lymphoid hyperplasia.

Epidemiology

Borrelial lymphocytoma, occurs primarily in Europe, in areas in which the Ixodes ricinus tick is endemic (Scandinavia, parts of Austria and Eastern Europe). In Europe incidence >50 cases/100,000 inhabitants/year (France 2017). Almost absent in the USA, where Borrelia burgdorferi sensu stricto is prevalent.

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Clear epidemiological data on Borrelia lymphocytoma are lacking. Around 1-2% of cases are reported. In a German survey from 2003, 189 out of 3935 borrelia infected patients (4.8%) developed lymphadenosis cutis benigna.

Definition

Harmless, reactive pseudolymphomatous infiltrate with follicular structures, which simulates cutaneous B-cell lymphoma (CBCL).

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Reactive pseudolymphomatous infiltrate with hyperplasia of lymphatic cells in the early phase after borrelia infection, but sometimes after viral or parasitic infections.

Aetiology & Pathogenesis

Causative agents: Borrelia garinii and Borrelia afzelii living in the gut of Ixodes Ricinus are transferred to the human host within 24 hours following the tick bite and induce a lymphfollicle-like inflammatory reaction.

 

Rare forms include reactions following herpes zoster, scabies, Hirudo medicinalis (leeches).

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Lymphadenosis cutis benigna is a process that can simulate a cutaneous B-cell-lymphoma, but it behaves in a harmless manner. It is a reactive process. In this type of pseudolymphoma, B – lymphocytes and other inflammatory cells accumulate in the dermis and subcutis as a reaction to stimuli of borrelia antigens.

This specific subset of B- cell type pseudolymphoma, borrelial lymphocytoma, primarily occurs in Europe in areas endemic for the tick Ixodes ricinus. Borrelial lymphocytoma is a tick bite response to infection by Borrelia burgdorferi subsp afzelius and garinii. Causative agents: Borrelia garinii and Borrelia afzelii (both in Europa), not Borrelia burgdorferi sensu strictu.

There are rare reports linking this type of pseudolymphomas to post-viral infections, in particular herpes zoster (post-zoster scar lymphocytoma cutis). Another established subtype is due to persisting reactions to the scabies mite without active but probably mite remnant involvement (persistent nodular arthropod-bite reactions).

Signs & Symptoms

Different forms: Soft, indolent, red-blue nodules (up to 5 cm) or infiltrated plaques; mostly solitary sometimes multiple. A lupoid infiltrate is seen with diascopy (under glass slide ); occasionally with lymphadenopathy.

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In Borrelia lymphocytoma lesions are often indolent soft blue-red nodules up to 5 cm. Post scabies lymphocytomas are localized or often disseminated.

Localisation

Sites of predilection: loose skin (ear, nipple, scrotum).

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Sites of predilection: In borrelia lymphocytoma the sites of predilection are: loose skin (ear, nipple, scrotum); red-blue lupoid infiltrate (diascopy).

Classification

None.

Laboratory & other workups

Borrelia IgG and IgM titers. Dermatopathology with immunochemistry. Blood cell count.

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Borrelia IgG and IgM titers raised in Borrelia lymphocytoma. No specific antigen subtype in serology to be detected. Dermatopathology specimen with immunohistochemistry necessary.

Dermatopathology

Typical B-cell pattern infiltrate, simulating an ectopic secondary (reactive antigen triggered) sharp demarcated nodular lymph follicle in the dermis, composed of small (centrocytes) and large (centroblasts) polyclonal B-lymphocytes (expression of B-cell-epitopes CD20, CD79a)  and many macrophages with inclusions (tingible bodies) in the follicular center, accompanied by polyclonal (mixed kappa and lambda light chains) plasma cells and varying number of eosinophils. No monoclonal rearrangement of immunoglobulins heavy or light chains.

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Most important is to differentiate the subtypes of pseudolymphomas (see chapter 3.3.14 Pseudolymphomas) and to exclude malignant B-or T-cell infiltrates from skin or systemic lymphomas. Epidermis not involved. Dermis with V-pattern top down mature relatively sharp demarcated nodular infiltrates of lymphocytes, plasma cells, follicle center cells, macrophages and sometimes eosinophils. Characteristic is an infiltrate-free zone beneath the epidermis. Expression of B-cell-epitopes (CD20, CD79a). No monoclonal rearrangement of immunoglobulins of heavy or light chains. Sometimes it will show a picture of mature lymph node tissue.

Course

Often heal spontaneously within weeks or some months or following adequate treatment; in contrast to malignant CBCL.

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Depends on subtype. In borrelia lymphocytoma after adequate 2nd stage oral doxycycline over 3 weeks, slow fading of lesion(s). In post-scabies pseudolymphoma after adaequate internal antiparasitic drugs and additional change of topical agent, complete but slow healing. Post herpes scar lymphocytoma up to 1-2 months healing.

Complications

None.

Diagnosis

Clinical features, serology, histology, PCR.

Differential Diagnosis

Malignant B- / T- cell lymphomas, cutaneous sarcoidosis, secondary syphilis

Prevention & Therapy

Antibiotics (doxycycline 100 mg b.i.d. for 3 weeks). Topical glucocorticosteroids may be effective (apoptosis of lymphocytes).

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Depending on subtype. Antibiotics (doxycycline 100 mg b.i.d. for 3 weeks) in borrelia lymphocytoma. Ivermectin orally for post scabies manifestation. Post herpes zoster scar pseudolymphoma topical corticosteroids are recommended.

Special

None.

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