Lymphocytoma cutis

Published on 19/03/2015 by admin

Filed under Dermatology

Last modified 22/04/2025

Print this page

rate 1 star rate 2 star rate 3 star rate 4 star rate 5 star
Your rating: none, Average: 2 (2 votes)

This article have been viewed 5513 times

[level-membership-for-dermatology-category]

Lymphocytoma cutis

Fiona J. Child and Sean J. Whittaker

Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports

image

Lymphocytoma cutis (cutaneous lymphoid hyperplasia, cutaneous B-cell pseudolymphoma, Spiegler–Fendt sarcoid) is an entity encompassing a spectrum of benign B-cell lymphoproliferative diseases that share clinical and histopathologic features. Various stimuli can induce lymphocytoma cutis, but in most cases the cause is not known. It is more common in females, with a female-to-male ratio of 3 : 1. Most cases are characterized by localized erythematous, plum-colored nodules and plaques that may be difficult to distinguish from cutaneous B-cell lymphoma. Less frequently the generalized form may present with multiple miliary papules that measure a few millimeters in diameter. Lymphocytoma cutis secondary to Borrelia infection is most frequently seen at sites where skin temperature is low, such as the earlobes, nipples, nose, and scrotum.

Management strategy

A skin biopsy for histopathology and immunohistochemistry is required to confirm the diagnosis, but the distinction between lymphocytoma cutis and cutaneous B-cell lymphoma may be difficult on both clinical and histopathologic evaluation. There are no agreed histologic criteria; however, features that suggest lymphocytoma cutis include well-formed, non-expanded, reactive germinal centers, the majority of the infiltrate consisting of small round lymphocytes with a B:T cell ratio of <3 : 1 and polytypic expression of kappa and lambda light chains. A further feature is the presence of numerous tingible body macrophages within the lymphoid follicles. Molecular analysis of the immunoglobulin heavy chain gene has shown that a significant proportion harbor B-cell clones, which suggests that many cases previously thought to be lymphocytoma cutis represent indolent low-grade primary cutaneous B-cell lymphomas (PCBCL). Therefore, in cases with a detectable B-cell clone a careful evaluation to exclude systemic disease (a thorough clinical examination, thoracoabdominopelvic CT scan, and bone marrow biopsy) is required, with adequate long-term follow-up.

A history of possible stimuli known to cause lymphocytoma cutis should be sought; these include Borrelia burgdorferi infection, Leishmania infection, trauma, vaccinations, allergy hyposensitization injections, ingestion of drugs, arthropod bites, acupuncture, gold pierced earrings, tattoos, treatment with leeches (Hirudo medicinalis), and post herpes zoster scars, but the majority of cases are of unknown etiology.

The course of the disease varies but tends to be chronic and indolent, and some lesions may resolve spontaneously without treatment. There is no therapy of proven value for lymphocytoma cutis, with only anecdotal case reports and small series reported and no clinical trials in the literature.

If a cause can be identified, the causative agent should be removed. If infection with Borrelia burgdorferi is suspected, treatment with appropriate antibiotics (amoxycillin 500–1000 mg three times per day, or doxycycline 100 mg two to three times per day for at least 3 weeks) should be initiated.

Localized disease can be treated by simple excision and may respond to intralesional injection of corticosteroids, local irradiation, or intralesional interferon-α. More widespread (generalized) disease is traditionally treated with oral antimalarials, most commonly hydroxychloroquine (maximum dose 6.5 mg/kg/day); however, lesions may fail to respond to treatment or may recur following cessation of therapy. Other treatment modalities include subcutaneous interferon-α and oral thalidomide. Effective responses to destructive therapies, including cryotherapy and the argon laser, have been reported. A subtype of generalized lymphocytoma cutis may be exacerbated by light, and therefore sun avoidance and the use of sun block are important.

Specific investigations

Polymerase chain reaction analysis of immunoglobulin gene rearrangement analysis in cutaneous lymphoid hyperplasias.

Bouloc A, Delfau-Larue M-H, Lenormand B, Meunier F, Wechsler J, Thomine E, et al. Arch Dermatol 1999; 135: 168–72.

Twenty-four patients with a diagnosis of lymphocytoma cutis according to clinical, histopathologic, and immunophenotypic criteria underwent PCR analysis of the immunoglobulin heavy chain gene using DNA from lesional skin. In one patient a B-cell clone was detected. In the other 23 a polyclonal result was obtained.

Cutaneous B-cell lymphomas are known to have a relatively high false-negative rate using PCR owing to somatic hypermutation, which affects the variable region of the immunoglobulin heavy chain gene and may prevent primer binding. The number of false-negative results may be significantly reduced by using multiple primer sets for different parts of the variable region and for the kappa light chain gene. This paper only used one set of primers, and therefore the detection of only one B-cell clone may be a significant underestimate.

First-line therapies

Localized  
imageExcision E
imageTopical corticosteroids E
imageIntralesional corticosteroids E
imageOral antibiotics (if positive Borrelia serology) E
imageCO2 or Nd:YAG laser (if occurring within a tattoo) E
Generalized  
imageAntimalarials E
imageSun avoidance/sun block (light exacerbated) E

Second-line therapies

Localized  
imageSuperficial radiotherapy E
imageIntralesional interferon-α E
imageArgon laser E
imageCryotherapy D
imageTopical 0.1% tacrolimus ointment E
imageIntralesional rituximab E
imageTopical photodynamic therapy E
Generalized  
imageSubcutaneous interferon-α2b E
imageThalidomide E

[/level-membership-for-dermatology-category][not-level-membership-for-dermatology-category]

Lymphocytoma cutis

Fiona J. Child and Sean J. Whittaker

Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports

image

Lymphocytoma cutis (cutaneous lymphoid hyperplasia, cutaneous B-cell pseudolymphoma, Spiegler–Fendt sarcoid) is an entity encompassing a spectrum of benign B-cell lymphoproliferative diseases that share clinical and histopathologic features. Various stimuli can induce lymphocytoma cutis, but in most cases the cause is not known. It is more common in females, with a female-to-male ratio of 3 : 1. Most cases are characterized by localized erythematous, plum-colored nodules and plaques that may be difficult to distinguish from cutaneous B-cell lymphoma. Less frequently the generalized form may present with multiple miliary papules that measure a few millimeters in diameter. Lymphocytoma cutis secondary to Borrelia infection is most frequently seen at sites where skin temperature is low, such as the earlobes, nipples, nose, and scrotum.

Management strategy

A skin biopsy for histopathology and immunohistochemistry is required to confirm the diagnosis, but the distinction between lymphocytoma cutis and cutaneous B-cell lymphoma may be difficult on both clinical and histopathologic evaluation. There are no agreed histologic criteria; however, features that suggest lymphocytoma cutis include well-formed, non-expanded, reactive germinal centers, the majority of the infiltrate consisting of small round lymphocytes with a B:T cell ratio of <3 : 1 and polytypic expression of kappa and lambda light chains. A further feature is the presence of numerous tingible body macrophages within the lymphoid follicles. Molecular analysis of the immunoglobulin heavy chain gene has shown that a significant proportion harbor B-cell clones, which suggests that many cases previously thought to be lymphocytoma cutis represent indolent low-grade primary cutaneous B-cell lymphomas (PCBCL). Therefore, in cases with a detectable B-cell clone a careful evaluation to exclude systemic disease (a thorough clinical examination, thoracoabdominopelvic CT scan, and bone marrow biopsy) is required, with adequate long-term follow-up.

A history of possible stimuli known to cause lymphocytoma cutis should be sought; these include Borrelia burgdorferi infection, Leishmania infection, trauma, vaccinations, allergy hyposensitization injections, ingestion of drugs, arthropod bites, acupuncture, gold pierced earrings, tattoos, treatment with leeches (Hirudo medicinalis), and post herpes zoster scars, but the majority of cases are of unknown etiology.

The course of the disease varies but tends to be chronic and indolent, and some lesions may resolve spontaneously without treatment. There is no therapy of proven value for lymphocytoma cutis, with only anecdotal case reports and small series reported and no clinical trials in the literature.

If a cause can be identified, the causative agent should be removed. If infection with Borrelia burgdorferi is suspected, treatment with appropriate antibiotics (amoxycillin 500–1000 mg three times per day, or doxycycline 100 mg two to three times per day for at least 3 weeks) should be initiated.

Localized disease can be treated by simple excision and may respond to intralesional injection of corticosteroids, local irradiation, or intralesional interferon-α. More widespread (generalized) disease is traditionally treated with oral antimalarials, most commonly hydroxychloroquine (maximum dose 6.5 mg/kg/day); however, lesions may fail to respond to treatment or may recur following cessation of therapy. Other treatment modalities include subcutaneous interferon-α and oral thalidomide. Effective responses to destructive therapies, including cryotherapy and the argon laser, have been reported. A subtype of generalized lymphocytoma cutis may be exacerbated by light, and therefore sun avoidance and the use of sun block are important.

Specific investigations