Non-flexural granulomatous slack skin associated with papules

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A 50-year-old man presented to the dermatology clinic with a three-month history of occasionally pruritic erythematous papules on the abdomen, limbs, and, back of the neck. A detailed history and physical examination revealed 20-year-old lax erythematous plaques on the right breast [Figure 1a], lumbosacral region, and, both calves. The condition initially manifested on both calves, followed by erythematous papules on the right breast and lumbosacral area, which gradually started sagging significantly. The axillae and groins were uninvolved. He had intermittently sought medical attention over the past 20 years and was diagnosed with cutis laxa without biopsy confirmation. However, the treatment was not consistent. Erythematous papules were noted on the neck, trunk, and limbs [Figures 1b-1d]. There was no significant lymphadenopathy and, ultrasound scan of the peripheral lymph nodes showed no significant abnormalities. He had no systemic symptoms.

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Figure 1:

(a) Lax erythematous plaque on the right breast, (b) Scattered erythematous papules on the abdomen and forearms, (c) Multiple erythematous papules on the back of the neck, (d) Lax erythematous plaques on the inner side of the calf, with multiple scattered erythematous papules on both legs .

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We considered the diagnosis of granulomatous slack skin (GSS). Uncertain of the association between the erythematous papules and the lax plaques, biopsies were taken from both types of lesions. Histopathology of the abdominal papule revealed nodular distribution of histiocytes, multinucleated giant cells containing numerous nuclei and lymphocytes in the upper dermis without significant epidermotropism or papillary dermal band-like infiltration [Figure 2a]. Victoria Blue-Ponceau S staining showed no dermal elastic fibre disruption. Immunohistochemistry (IHC) showed lymphocytes expressing CD3 and CD5, partial loss of CD7, more CD4⁺ than CD8⁺ cells and histiocytes expressing CD68. Histopathology of the lax plaques showed full-thickness dermal and subcutaneous infiltration of lymphocytes, histiocytes, and multinucleated giant cells, with a band-like distribution in the dermal papillae lacking significant epidermotropism [Figure 2b]. Elastic fibre staining revealed significant dermal elastic fibre fragmentation [Figure 2c]. On IHC, lymphocytes were positive for CD2, CD3 and CD5, with a higher expression of CD4⁺ cells than CD8⁺ cells, partial loss of CD7, negative for CD20 and CD30, and histiocytes positive for CD68 [Figures 2d-2f].

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Figure 2a:

Abdominal papule showing full-thickness dermal and subcutaneous infiltration of lymphocytes, histiocytes, and multinucleated giant cells with a band-like distribution in the dermal papillae and lacking significant epidermotropism (Haematoxylin & eosin, 100×).

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Figure 2b:

Lax plaque showing infiltration of lymphocytes, histiocytes, and multinucleated giant cells in the entire dermis and subcutaneous fat with a band-like distribution in the papillary dermis (Haematoxylin & eosin, 40×).

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Figure 2c:

The elastic fibres in the dermis are broken, and only a small amount of elastic fibres remained in the papillary dermis of lax plaque (Victoria Blue-Ponceau S staining, 400×).

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Figure 2d:

The lymphocytes in the belt-like infiltration expressed CD3 in lax plaque (Immunohistochemical staining, 100×).

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Figure 2e:

Most of the lymphocytes in the belt-like infiltration expressed CD4 in lax plaque (Immunohistochemical staining, 100×).

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Figure 2f:

Scattered multinucleated giant cells expressed CD68 in lax plaque (Immunohistochemical staining, 100×).

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Our patient was treated with oral methotrexate 10 mg once a week and prednisone 20 mg once a day, topical nitrogen mustard application, and narrowband UVB therapy. After three months, the erythematous papules significantly flattened [Figures 3a-c], and the lax erythematous plaques faded and became soft, but skin laxity showed no improvement.

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Figure 3:

(a) Reduction and flattening of papules on the abdomen and forearms after three months of treatment, (b) Reduction and flattening of papules on the back of the neck after three months of treatment, (c) The lax erythematous plaques on the inner side of the left calf faded, and the erythematous papules on the legs reduced and flattened after three months of treatment.

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GSS is a rare subtype of mycosis fungoides with an insidious course. Typical lesions include lax plaques in the axillae and groins. In this patient, the lax skin lesions mainly involved the non-flexural sites and generalised papules emerged all over the body much later after the formation of lax plaques. Papular skin lesions are rare in GSS and may indicate disease progression.¹ However, the papules improved rapidly after treatment in our case.

Histologically, GSS may be misdiagnosed as granulomatous dermatitis due to the rarity of epidermotropism and prominent histiocytic and multinucleated giant cell proliferation. Differential diagnosis includes other lymphomas with granuloma formation, especially granulomatous mycosis fungoides, which has fewer multinucleated giant cells and lacks significant elastic fibre fragmentation. Moreover, clinical presentation is essential for differentiation.

Granuloma formation may result from tumorigenic CD4⁺ T lymphocytes attracting histiocytes. Spatial transcriptomics of these histiocytes has shown strong expression of matrix metalloproteinase 9 (MMP9) related to extracellular matrix degradation and tissue remodelling, potentially causing elastic tissue destruction and leading to lax skin plaques.^2,3

Treatment of GSS is challenging and includes topical and systemic corticosteroids, nitrogen mustard, retinoids, methotrexate, interferons, azathioprine, PUVA, radiotherapy,, and chemo-immunotherapy. Reported cases have shown variable responses, with recurrence after surgical excision of lax skin and without complete remissions. A retrospective multicentre study showed a 100% 5-year survival rate for GSS, but 25% patient mortality in those developing secondary lymphomas, especially anaplastic large cell lymphoma and Hodgkin lymphoma, necessitating lifelong follow-up.^4,5

In conclusion, as far as ascertained, no reports of GSS with generalised papules exist. Appearance of papules complicates clinical diagnosis with atypical histology, requiring caution on the part of dermatologists and pathologists. Although the papules significantly reduced and flattened after short-term treatment, it is still unknown whether these papules would have developed into lax plaques. Long-term observation is needed, and attention with respect to the occurrence of secondary lymphoma is necessary.