Granulomatous Slack Skin Research Articles

Granulomatous Slack Skin With Lung and Esophagus Involvement: A Case Report and Molecular Analysis.

Granulomatous slack skin (GSS) is a rare subtype of mycosis fungoides, and few cases have been known to spread to the blood, lymph nodes, or viscera. We present a case with early dissemination to the lung. A 27-year-old woman, previously healthy, presented with scattered disseminated scaly patches, associated with vulvar and intergluteal firm swelling and groin-skin induration for 1 year. She also reported mild fatigue and breathlessness on moderate exertion. The patient underwent blood tests, skin biopsies, and computed tomography scan. The skin biopsy showed a mildly atypical T-cell lymphoid infiltrate involving the dermis/hypodermis, with focal epidermotropism, associated with a granulomatous infiltrate and elastophagocytosis. The computed tomography scan revealed bilateral ground-glass lung nodular opacities. Positron emission tomography showed an increased signal in the skin and subcutis around the buttocks, inguinal and mediastinal lymph nodes, and lungs. The lung biopsy confirmed a dense T-cell infiltrate with numerous multinucleated giant cells. Subsequently, esophageal involvement was also observed following biopsy. Molecular analyses demonstrated identical T-cell clones in the skin and lung. After 6 cycles of chemotherapy/localized external radiotherapy, the patient had a partial skin response and stable lung disease. A preferred diagnosis of GSS with systemic spread was made based on clinical/histologic/molecular findings, after considering granulomatous mycosis fungoides and peripheral T-cell lymphoma, not otherwise specified. This case highlights the frequent diagnostic difficulty in distinguishing GSS from an inflammatory granulomatous dermatitis. Pulmonary and esophageal involvements are rare in GSS, and the simultaneous presentation of characteristic cutaneous GSS with systemic disease poses an additional classification challenge.

A rare case of granulomatous slack skin with scarce multinucleated giant cells

A rare case of granulomatous slack skin with scarce multinucleated giant cells

Mycosis Fungoides and Granulomatous Slack Skin: A Single Entity With Distinct Clinical Phenotypes.

Granulomatous cutaneous T-cell lymphoma includes mycosis fungoides with significant granulomatous inflammation (GMF) and granulomatous slack skin (GSS), listed in the WHO classification as a subtype of mycosis fungoides (MFs).1 These overlapping entities have shared clinical and histopathologic features which can present a diagnostic challenge. The dominance of the granulomatous infiltrate and the often sparse lymphocytic infiltrate frequently with minimal cytological atypia are features that distract from the correct diagnosis, even when raised by the clinician. We describe the clinical and histopathologic characteristics of 3 cases of granulomatous cutaneous T-cell lymphoma, illustrate the close clinical and pathologic relationship between GMF and GSS and emphasize the diagnostic difficulties that the granulomatous infiltrate can present. Furthermore, we demonstrate, for the first time, considerable elastolysis in a significant proportion of classical (Alibert-Bazin) MF lesions and therefore postulate that the differences observed between GMF and GSS are one of degree and secondary to their anatomic location rather than reflecting meaningful separate entities.

Spatial transcriptomics reveals heterogeneity of macrophages in the tumor microenvironment of granulomatous slack skin.

Granulomatous slack skin (GSS) is an extremely rare subtype of cutaneous T-cell lymphoma accompanied by an abundant number of macrophages and is clinically characterized by the development of pendulous skin folds. However, the characteristics of these macrophages in GSS remain unclear. Here, we conducted a spatial transcriptomic study on one frozen GSS sample and drew transcriptomic maps of GSS for the first time. Gene expression analysis revealed the enrichment of three clusters with macrophage transcripts, each exhibiting distinct characteristics suggesting that their primary composition consists of different subpopulations of macrophages. The CD163+ /CD206+ cluster showed a tumor-associated macrophage (TAM) M2-like phenotype and highly expressed ZFP36, CCL2, TNFAIP6, and KLF2, which are known to be involved in T-cell interaction and tumor progression. The APOC1+ /APOE+ cluster presented a non-M1 or -M2 phenotype and may be related to lipid metabolism. The CD11c+ /LYZ+ cluster exhibited an M1-like phenotype. Notably, these cells strongly expressed MMP9, MMP12, CHI3L1, CHIT1, COL1A1, TIMP1, and SPP1, which are responsible for extracellular matrix (ECM) degradation and tissue remodeling. This may partially explain the symptoms of cutaneous relaxation in GSS. Further immunohistochemistry on four GSS cases demonstrated that CD11c predominantly marked granulomas and multinucleated giant cells, whereas CD163 was mainly expressed on scattered macrophages, appearing as a mutually exclusive pattern. The expression pattern of MMP9 overlapped with that of CD11c, implying that CD11c+ macrophages may be a source of MMP9. Our data shed light on the characteristics of macrophages in the GSS microenvironment and provide a theoretical basis for the application of MMP9 inhibitors to prevent cutaneous relaxation of GSS. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Mycosis fungoides and Sézary syndrome: clinical presentation, diagnosis, staging, and therapeutic management.

Mycosis fungoides (MF) and Sézary syndrome (SS) are cutaneous T-cell lymphomas. MF is the most common cutaneous lymphoma, and it is classified into classic Alibert-Bazin MF, folliculotropic MF, pagetoid reticulosis, and granulomatous slack skin, each with characteristic clinical presentation, histopathological findings, and distinct clinical behaviors. SS is an aggressive leukemic variant of cutaneous lymphoma, and it is characterized by erythroderma, lymphadenopathy, and peripheral blood involvement by malignant cells. There is a wide range of dermatological manifestations of MF/SS, and prompt recognition is essential for early diagnosis. Skin biopsy for histopathology and immunohistochemical analysis is imperative to confirm the diagnosis of MF/SS. Histopathology may also provide information that may influence prognosis and treatment. Staging follows the TNMB system. Besides advanced stage, other factors associated with poorer prognosis are advanced age, male gender, folliculotropism in histopathology of patients with infiltrated plaques and tumors in the head and neck region, large cell transformation, and elevated lactate dehydrogenase. Treatment is divided into skin-directed therapies (topical treatments, phototherapy, radiotherapy), and systemic therapies (biological response modifiers, targeted therapies, chemotherapy). Allogeneic bone marrow transplantation and extracorporeal photopheresis are other treatment modalities used in selected cases. This review discusses the main clinical characteristics, the histopathological/immunohistochemical findings, the staging system, and the therapeutic management of MF/SS.

Multidisciplinary Approach to the Diagnosis and Therapy of Mycosis Fungoides

Mycosis fungoides is the most common primary cutaneous T-cell lymphoma, characterized by skin-homing CD4+ T cells derivation, indolent course, and low-grade of malignancy. Mycosis fungoides's classic type typically onsets with cutaneous erythematous patches, plaque, and tumor. In WHO-EORTC classification, folliculotropic mycosis fungoides, pagetoid reticulosis, and granulomatous slack skin are recognized as distinct variants of mycosis fungoides, because of their clinical and histological features, behavior, and /or prognosis. Mycosis fungoides often shows diagnostic difficulties, due to its absence of specific features and lesional polymorphism. A patient's treatment requires staging. In about 10% of cases, mycosis fungoides can progress to lymph nodes and internal organs. Prognosis is poor at advanced stage and management needs a multidisciplinary team approach. Advanced stage disease including tumors, erythroderma, and nodal, visceral, or blood involvement needs skin directed therapy associated with systemic drugs. Skin directed therapy includes steroids, nitrogen mustard, bexarotene gel, phototherapy UVB, and photochemiotherapy, i.e., total skin electron radiotherapy. Systemic therapies include retinoids, bexarotene, interferon, histone deacetylase inhibitors, photopheresis, targeted immunotherapy, and cytotoxic chemotherapy. Complexity of mycosis fungoides associated with long-term chronic evolution and multiple therapy based on disease stage need a multidisciplinary team approach to be treated.

Granulomatous Slack Skin with Hypercalcemia Indolently Mimicking Sarcoidosis

<p class="abstract">Granulomatous slack skin is a rare variant of cutaneous T-cell lymphoma characterized by lax skin and granulomatous infiltrate with loss of elastic fibers on histology. We report a unique case of a female presenting with CD30-granulomatous slack skin complicated by hypercalcemia, initially diagnosed, and managed as sarcoidosis. Interestingly, she had a history of previously treated CD30+ cutaneous T-cell lymphoma. Granulomatous slack skin can frequently mimic other benign and malignant cutaneous diseases, prompting the need for clinical vigilance from dermatologists.</p>

Epi-O-07 - Granulomatous slack skin: clinical retrospective study of 8 cases of the Cutaneous Lymphoma French Study Group

Granulomatous slack skin (GSS) is a rare variant of mycosis fungoides (MF) presenting clinically as pendulous and lax plaques or tumours and histologically as a dermal infiltrate of neoplastic T-cells with multinucleated giant cells, loss of dermal elastin fibres and sometimes elastophagocytosis and lymphophagocytosis. Because of its scarcity, GSS is poorly known. The aim of this study was to describe the clinical and evolutive features and the response to treatment of a GSS cohort. In this retrospective multicenter study, we have identified the cases of GSS in the Cutaneous Lymphoma French Study Group database and member centers.

Hist-O-01 - Pustular mycosis fungoides has a poor outcome: a clinico-pathological and longitudinal study of 36 cases

Introduction: Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma. Three variants are described in the last WHO 2018: folliculotropic, pagetoid and granulomatous slack skin. The evolution is chronic with a 5-year survival of 88%. The prognosis depends on age, clinical stage, and histological transformation into large cells. Pustular variants of MF (pMF) are rare. Isolated case reports suggest that pMF may have unfavorable prognosis. We conducted a prospective study of a series of pMF to further describe their clinical and pathological cahacteristics and outcome.

Characteristics and outcomes of 727 patients with mycosis fungoides and Sézary syndrome from a Brazilian cohort.

Mycosis fungoides (MF) and Sézary syndrome (SS) are the most prevalent cutaneous lymphomas. They were not described in a large Brazilian cohort yet. We aimed, with this single-center, retrospective cohort analysis, to describe the characteristics and outcomes of MF/SS in a tertiary public health service in Brazil. MF/SS patients evaluated at the University of São Paulo Medical School between 1989 and 2018 were included. Data were collected at diagnosis. Demographic, clinical, histopathological, immunopathological, molecular, laboratory, and follow-up data were analyzed. Among 727 patients, 92.6% (673) were diagnosed with MF, 7.4% (54) with SS. There were 51.2% (372) of males, 48.8% (355) of females. The median age was 51.8 years; it was higher in erythrodermic MF (60.2) and SS (60.9). Among MF, 41.8% (281) had classic MF, 4.9% (33) folliculotropic MF, 1.8% (12) granulomatous slack skin, and 0.3% (2) pagetoid reticulosis. Common subtypes included erythrodermic (14.1%, 95), hypopigmented (10.8%, 73), and poikilodermatous MF (10.8%, 73). Extracutaneous involvement was rare. Five, 10, 20, and 30-year overall survival rates were 97.3%, 92.4%, 82.6%, and 82.6% for early-stage, and 58.6%, 42.7%, 20.8%, and 15.4% for advanced-stage disease, respectively. After multivariate analysis, SS diagnosis, folliculotropic MF, erythrodermic MF, clinical stage, age (≥60 years), increased lactate dehydrogenase, and large cell transformation conferred poorer prognosis. We observed a higher percentage of hypopigmented MF compared to the literature, and demographic (older age) and prognostic (poorer prognosis) similarities between erythrodermic MF and SS, suggesting a possible relationship between these erythrodermic lymphomas. Factors associated with a poorer prognosis were compatible with the literature.

Primary cutaneous T-cell lymphomas in childhood and adolescence.

Primary cutaneous lymphomas are extranodal non-Hodgkin lymphomas of T- or B- cell origin, that predominantly affect older patients but have been reported in all age groups and as early as in the first years of life. Diagnosis of cutaneous lymphomas is challenging and requires high clinical suspicion and close collaboration between dermatologists, pediatric oncologists and pathologists. Skin involvement of non-Hodgkin lymphomas in children or adolescents can either be primary cutaneous or secondary due to an underlying nodal lymphoma. The most common primary cutaneous lymphomas encountered in children are of T-cell origin, with mycosis fungoides being the most prevalent cutaneous T-cell lymphoma, followed by CD30+ lymphoproliferative disorders. While cutaneous lymphomas share clinicopathologic characteristics between juvenile and adult forms, there are important differences in terms of clinical presentation, diagnosis and treatment. The hypopigmented variant of mycosis fungoides seems to be overrepresented in the pediatric age group. Prognosis and treatment of mycosis fungoides are stage dependent. The majority of children present with early-stage disease and respond well to topical corticosteroids and phototherapy.

Clinical variants of mycosis fungoides in a cohort.

Mycosis fungoides (MF) is the most common primary skin T-cell lymphoma, which is characterized for a heterogeneous clinical expressivity. To report clinical variants and sociodemographic characteristics in patients with MF under the care of a dermatological hospital. 290 patients with MF clinical and histopathological diagnosis attended to over the course of 11 years were included. Sociodemographic description of patients was made, who were classified according to clinical and histopathological variants. MF was recorded in 57.9 % of women and 42 % of men. The most common clinical variant was the classic type in 46.2 %; dyschromic variants accounted for 35.2 %, out of which hypopigmented MF was the most representative (17.6 %); poikilodermatous MF accounted for 4.1 %, and folliculotropic, for 3.1%. The papular variant occurred in six patients (2.1 %), the single-plaque variety in three (1%), and the ichthyosiform, syringotropic and granulomatous slack skin varieties occurred in one patient each. The granulomatous variant was found in 0.7 %, and 1.4 % had erythroderma. The most common MF clinical variant was classic plaque stage, followed by dyschromic variants. Other clinical variants accounted for 18.6 %.

Granulomatous Slack Skin T-Cell Lymphoma Manifesting as Ulcerative and Gangrenous Lesions With a Fatal Outcome: A Case Report and Review of the Literature

Abstract Granulomatous slack skin is an extremely rare cutaneous T-cell lymphoma, which often pursues an indolent disease course. Clinically, it is characterized by areas of redundant and lax skin in flexural areas, with variable erythema. Histologic findings include granulomatous T-cell infiltrates with loss of elastic fibers and poikilodermic change. In this article, we report a patient with unusual rapidly progressive ulcerative and gangrenous skin lesions, leading to amputation and ultimately demise. We also review the literature on granulomatous slack skin with similarly aggressive clinical course and discuss the differential diagnosis.

Outcome of a case of granulomatous slack skin, recalcitrant leg ulcers and pruritus, managed with Miculicz ointment and homeopathy

Outcome of a case of granulomatous slack skin, recalcitrant leg ulcers and pruritus, managed with Miculicz ointment and homeopathy

Granulomatous slack skin: case report with electron microscopic features

Granulomatous slack skin (GSS) is a rare subtype of mycosis fungoides. It usually presents as slowly evolving, erythematous, slack plaques that usually involve folds of lax skin. Herein, we report a case of GSS and we show electron microscopy examination. Atypical T cells with convoluted and cerebriform nuclei, lymphophagocytosis, and elastophagocytosis are key features of GSS under electron microscopy.

Granulomatous slack skin: A series of cases

Aims: Granulomatous slack skin (GSS) is a rare subtype of cutaneous T-cell lymphoma (CTCL), characterized by folds of lax skin, predominantly in flexural areas. Histopathology shows granulomatous interstitial infiltrate of atypical lymphocytes in the dermis with multinucleated giant cells, elastolysis, epidermotropism and emperipolesis. Neoplastic cells are CD4+CD8- or, less commonly, CD4-CD8+. There is no specific therapeutic regimen, and the disease is indolent with prolonged survival.

Granulomatous mycosis fungoides, with features of granulomatous slack skin. Co-morbidity with several visceral cancers, indolent course of the skin disease. Disparity of clinical picture and histopathology

Granulomatous mycosis fungoides, with features of granulomatous slack skin. Co-morbidity with several visceral cancers, indolent course of the skin disease. Disparity of clinical picture and histopathology

Mycosis fongoïde chalazodermique associé à un séminome testiculaire métastatique

Granulomatous slack skin (GSS) is an extremely rare subtype of T-cell lymphoma, a variant of mycosis fungoides (MF). Herein, we describe the first reported case of GSS associated with metastatic testicular seminoma. A 28-year-old male patient presented with circumscribed erythematous loose skin masses, especially in the body folds and which had been relapsing for 4years. Skin biopsy showed a loss of elastic fibers and an atypical granulomatous T-cell infiltrate with epidermotropism, enabling a diagnosis of GSS to be made. A biopsy of a retroperitoneal lymphadenopathy showed testicular seminoma metastasis. Patients suffering from GSS have a statistically higher risk of developing a second primary cancer, especially Hodgkin's lymphoma. The association found between GSS and a lymphoproliferative malignancy requires long-term follow-up and determines the patient's prognosis. It is not possible to prove a formal link between GSS and testicular seminoma. However, this case illustrates the value of screening for a second cancer, particularly where extra-cutaneous lesions appear during GSS treatment. Lymph node biopsy should be performed routinely in the event of GSS with possible lymph node involvement.

Clinicopathological analysis of six patients with granulomatous slack skin

Objective To investigate clinicopathological features of granulomatous slack skin (GSS) . Methods Clinical and pathological data were obtained from 6 cases of GSS, and analyzed retrospectively. Results All the 6 patients were males, and presented with slack plaques and even pendulous skin folds. These skin lesions mainly affected flexural areas in 5 patients, and only occurred in the right chest in 1 patient. One patient was diagnosed with GSS complicated by mycosis fungoides (MF) . Histopathological examination showed non-caseating granulomas with infiltration of medium-sized lymphoid cells and multinucleated giant cells in the dermis in all the patients, atypical lymphoid cells in 1 patient, and epidermotropism in another patient. Immunohistochemical study revealed monoclonal CD4+ lympho-cytosis. Elastic fiber staining was performed in 4 patients, and showed crimp, fracture and disappearance of elastic fibers, and elastic fiber phagocytized by multinuclear giant cells in 2 patients. There were monoclonal rearrangements of T-cell receptor (TCR) γ gene in 2 patients. After radiotherapy with electron beam or superficial X-ray, lesions of 2 patients became smaller, and then were excised completely without recurrence. The other 4 patients received intramuscular injection of interferon α-2b and topical application of 0.02% mechlore-thamine solution, and their condition was improved. Conclusions GSS has a slowly progressive course, and overtreatment is not recommended. Surgical excision may be the first choice for GSS localized in flexural areas. Key words: Lymphoma, T-cell, cutaneous; Cutis laxa; Mycosis fungoides; Skin manifestations; Pathology; Treatment outcome

Granulomatous slack skin associated with ALK-negative anaplastic large cell lymphoma

Granulomatous slack skin associated with ALK-negative anaplastic large cell lymphoma