Different histologic patterns of cutaneous granulomas in systemic lymphoma

doi:10.1016/j.jaad.2004.02.024

Journal of the American Academy of Dermatology

Volume 51, Issue 4, October 2004, Pages 600-605

https://doi.org/10.1016/j.jaad.2004.02.024 Get rights and content

Abstract

Background

Patients with Hodgkin's and non-Hodgkin's lymphomas may develop non-infectious granulomas in both involved and uninvolved organs, but rarely in the skin. Cutaneous granulomas in the setting of a systemic lymphoma are of two types. The first type is characterized by granulomatous infiltrates admixed with neoplastic cells within specific skin lesions of malignant lymphomas. The second type consists of granulomatous skin processes that are non-specific manifestations of the underlying lymphoma.

Objective

To describe the variegate histologic patterns of cutaneous granulomatous reactions of the second type in patients with systemic lymphomas.

Methods

We describe three patients with systemic lymphomas who exhibited three different histologic patterns of cutaneous granulomatous lesions.

Results

The first patient had non-Hodgkin's lymphoma with cutaneous tuberculoid-type granuloma mimicking tuberculoid leprosy; the second patient had Hodgkin's lymphoma with palisaded, necrobiotic granuloma of granuloma annulare-type; and the third patient had non-Hodgkin's lymphoma with sarcoid-type granuloma. No evidence of the underlying systemic lymphoma was found in the cutaneous lesions involved by the granulomatous process.

Conclusions

Cutaneous granulomas may be a non-specific sign of an underlying systemic lymphoma. Their histologic patterns are variegate and include sarcoid-type granuloma, palisaded and necrobiotic granuloma of granuloma annulare-type, and tuberculoid granuloma. In patients who present with non-infectious, granulomatous skin reactions in the absence of another sound explanation, the possibility of a systemic lymphoma should be considered.

Section snippets

Case 1

A 50-year-old woman, diagnosed as having high-grade T-cell lymphoma 3 years before our observation, had been treated with chemotherapy (8 cycles of VACOP-B) and autologous stem cell graft achieving an apparently good remission. She had lived in Sicily since her birth. She was referred to the Section of Dermatology, University of Genoa for a cutaneous eruption evolving for 1 year. Granuloma annulare and multicentric reticulohistocytosis had been tentatively diagnosed in another department.

Case 2

A 29-year-old man with enlarged bilateral hilar lymphadenopathy was diagnosed as having nodular sclerosing HL. He was treated with systemic chemotherapy (CHOP) and achieved complete clinical remission. Two years later, the patient developed dyspnea and a skin eruption. Chest X-ray revealed enlargement of mediastinum with pleural effusion of his right lung.

On examination, skin-colored, grouped papules forming arciform plaques were observed on the trunk, upper arms (Fig 5), thighs, and buttocks.

Case 3

A 48-year-old woman presented with a 5-month history of a skin eruption on her face and arms and bilateral laterocervical, axillary, and inguinal lymphadenopathies associated with fatigue and night sweats.

On examination, isolated and confluent erythematous papules were seen involving the face, trunk (Fig 7), and lower limbs. A skin biopsy of the arm revealed, under a normal epidermis, some non-caseating epithelioid granulomas scattered throughout the papillary and mid dermis without any

Discussion

Cutaneous granulomas can be observed in many cases of both primary cutaneous and systemic lymphomas. In this setting, an infectious etiology should be primarily ruled out by culture and/or special stains and techniques of molecular biology. Cutaneous non-infectious granulomas associated with malignant lymphomas may be of two types.³ The first type is characterized by granulomatous infiltrates admixed with neoplastic cells within specific skin lesions of malignant lymphoma. In fact, a prominent

References (21)

P.J. Gregg et al.
Sarcoidal tissue reaction in Sézary syndrome
J Am Acad Dermatol
(2000)
K.M. Diette et al.
Malignant lymphoma presenting with cutaneous granulomas
J Am Acad Dermatol
(1984)
S.K. Barksdale et al.
Granuloma annulare in patients with malignant lymphoma: Clinicopathologic study of thirteen new cases
J Am Acad Dermatol
(1994)
K. Dabski et al.
Generalized granuloma annulare: Clinical and laboratory findings in 100 patients
J Am Acad Dermatol
(1989)
H.Y. Pak et al.
Pseudosarcoid granulomas in Hodgkin's disease
Hum Pathol
(1981)
M.E. Kadin et al.
Isolated granulomas in Hodgkin's disease
N Engl J Med
(1970)
H. Brincker
The sarcoidosis-lymphoma syndrome
Br J Cancer
(1986)
L. Cerroni
Cutaneous granulomas and malignant lymphomas
Dermatology
(2003)
A. Scarabello et al.
Cutaneous lymphomas with prominent granulomatous reaction: A potential pitfall in the histopathologic diagnosis of cutaneous T- and B-cell lymphomas
Am J Surg Pathol
(2002)
P.E. LeBoit et al.
Granulomatous variants of cutaneous T-cell lymphoma: the histopathology of granulomatous mycosis fungoides and granulomatous slack skin
Am J Surg Pathol
(1988)

There are more references available in the full text version of this article.

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En esta serie de 2 artículos realizamos una revisión de las principales entidades dermatopatológicas que cursan con granulomas. Esta primera parte se ha centrado en la aclaración de los conceptos, la presentación de los tipos de granulomas y de las células gigantes, así como en entidades muy diversas de origen no infeccioso. Algunas de ellas de origen metabólico, como la necrobiosis lipoídica: otras relacionadas con linfomas, como la micosis fungoides granulomatosa, y otras tan extendidas que casi resultan un problema cotidiano en las consultas de dermatología, como la rosácea.
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Citation Excerpt :
The significance of these unusual granulomatous findings in the setting of scleromyxedema is unclear. It can be speculated that this reaction represents an immunologic response to the monoclonal gammopathy associated with scleromyxedema, as previously suggested for the granulomatous response to lymphomas.23 Our large case series of patients with scleromyxedema focuses on the histologic appearance of the disease.
Few histologic studies describe the histopathologic aspects of scleromyxedema.
We sought to describe the histopathologic and immunohistochemical features of scleromyxedema in a large series of patients.
We studied all the cases with scleromyxedema diagnosed between 2000 and 2014 at participating centers. Sections with hematoxylin-eosin and special stains were examined. Immunohistochemistry for CD3, CD4, CD8, CD20, CD68, and factor XIIIa was performed in 10 cases.
A total of 44 skin biopsy specimens from 34 patients were reviewed. Two different histopathologic patterns were observed: the classic microscopic triad (dermal mucin deposition, fibroblast proliferation, fibrosis) was identified in 34 specimens, whereas an interstitial granuloma annulare–like pattern was found in 10 specimens. A superficial perivascular infiltrate with T lymphocytes was found in all specimens whereas an interstitial proliferation of CD68⁺ epithelioid cells was identified in the 10 specimens with an interstitial granuloma annulare–like pattern. Elastic fibers were largely lost, explaining the redundant folds of the disease.
This was a retrospective study.
Scleromyxedema shows 2 histopathologic patterns, including the classic type with the microscopic triad of mucin, fibroblast proliferation and fibrosis, and an interstitial granuloma annulare–like pattern. Recognition of these histologic presentations expands the spectrum of scleromyxedema and highlights the difficulty in diagnosing this disabling condition in the absence of a clinicopathological correlation.
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Granulomatous cutaneous T-cell lymphoma (G-CTCL) is a rarely encountered entity. Most G-CTCL is CD4⁺, with granulomatous mycosis fungoides representing the vast majority of cases. Because of the rarity of CD8⁺ G-CTCL, there is a paucity of data regarding the clinicopathologic features and expected course.
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This is a retrospective review of collected cases.
We present 4 cases of CD8⁺ G-CTCL. Patients presented with papules and nodules on the trunk and extremities without antecedent patch or plaque disease. In all cases, biopsy specimens were obtained, and these revealed a dense granulomatous infiltrate accompanied by an atypical lymphoid infiltrate of CD8⁺ T cells. T-cell clonality studies were positive in 3 of 4 cases. Staging was negative for nodal involvement, but lung granulomas were seen in all cases. In all 4 cases, the patient's medical history was significant for immunodeficiency, either primary or iatrogenic. All 4 patients had slowly progressive disease.
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The male-to-female ratio seems increased (2.9:1), and the age of onset is wide ranging from childhood to elderly. The histologic features of GSSS are characterized by a diffuse infiltrate throughout the entire dermis of small to medium-sized lymphocytes, more commonly with interstitial granulomatous changes and scattered multinucleated giant cells.37 Multinucleated giant cells displaying between 20 and 30 nuclei per cell is considered a pathognomonic feature.38,39
Mycosis fungoides (MF) is a cutaneous T-cell lymphoma that usually manifests as patches and plaques with a propensity for nonphotoexposed areas. MF is a common mimicker of inflammatory and infectious skin diseases, because it can be manifested with a wide variety of clinical and pathologic presentations. These atypical presentations of MF may be difficult to diagnose, requiring a high level of suspicion and careful clinicopathologic correlation. Within this array of clinical presentations, the World Health Organization classification recognizes 3 MF variants: folliculotropic MF, pagetoid reticulosis, and granulomatous slack skin. These 3 variants, as well as hypopigmented MF, are addressed in this article.

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Funding sources: None.

Conflicts of interest: None identified.

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DermatopathologyDifferent histologic patterns of cutaneous granulomas in systemic lymphoma☆

Abstract

Background

Objective

Methods

Results

Conclusions

Section snippets

Case 1

Case 2

Case 3

Discussion

J Am Acad Dermatol

J Am Acad Dermatol

J Am Acad Dermatol

J Am Acad Dermatol

Hum Pathol

Isolated granulomas in Hodgkin's disease

N Engl J Med

The sarcoidosis-lymphoma syndrome

Br J Cancer

Cutaneous granulomas and malignant lymphomas

Dermatology

Cutaneous lymphomas with prominent granulomatous reaction: A potential pitfall in the histopathologic diagnosis of cutaneous T- and B-cell lymphomas

Am J Surg Pathol

Granulomatous variants of cutaneous T-cell lymphoma: the histopathology of granulomatous mycosis fungoides and granulomatous slack skin

Am J Surg Pathol

Dermatopathology
Different histologic patterns of cutaneous granulomas in systemic lymphoma☆