Interstitial Granuloma Annulare Research Articles

Clinicopathologic evaluation of granuloma annulare: Study of 136 Iranian cases, south of Iran.

Granuloma annulare (GA) is a benign skin disorder with various histopathologic features that are rarely investigated in Iranian population. We performed this study to find out the clinical and histopathologic features of GA in our referral centre. One hundred-thirty-six patients with biopsy-proven GA were reviewed. Clinical data and pathological features were recorded. One hundred-eight female patients and 28 male patients (Female/male ratio: 3.85) with mean age of 42.54±21.2years (range: 2-83years) were recruited. Eighty-eight (64.7%) patients had interstitial infiltrative pattern and 48 (35.3%) patients had complete palisading granulomas. The infiltrate occupied both upper and lower dermis in most of the cases (67.7%). Significant mucin was detected more commonly in complete GA compared to interstitial GA (p=0.019), but inflammation degree, eosinophils, plasma cells, and giant cells were not different between two subtypes of GA (p>0.05). The significant inflammation contained more significant plasma cells (p=0.006). The significantly more giant cells were detected in patients between 20 and 60years of age (p=0.015); but other factors were not different between age groups. In our study, the prevalence of GA in women was significantly higher than in men. Interstitial GA was the more common histological subtype and the inflammation was less severe and the infiltrate was mostly pandermal in our cases. More severe inflammation contained more plasma cells, and more dense giant cells were seen in middle aged patients.

Penile granuloma annulare: An uncommon entity

Granuloma annulare (GA) is a benign inflammatory disorder of unknown etiology, histologically characterized by dermal palisading granulomas with central degeneration of collagen. Involvement of the penis is exceptional and lesions restricted only to the glans penis are rarely reported. We report a middle-aged male, presenting with asymptomatic plaques on the glans penis which on biopsy proved to be interstitial GAs. Penile GA seldom shows spontaneous resolution as in our case. Penile GA although rare should be considered in the differential diagnosis of granulomatous lesions of the penis and histological examination is crucial for its diagnosis to avoid over-treatment.

Hist-O-08 - Macular type of primary cutaneous B-cell lymphoma: extension of the clinical and histopathological patterns

<h3>Importance:</h3> Primary cutaneous B-cell lymphoma (PCBCL) classically presents with papules, plaques, nodules/ tumors. Previous reports of PCBCL manifesting with macular lesions are scarce, and focused on primary cutaneous follicle-center cell lymphoma (PCFCL), with limited data on its clinicopathological correlation. <h3>Objective:</h3> To report our experience with PCBCL presenting with erythematous macules. <h3>Design:</h3> Retrospective cohort. <h3>Setting:</h3> Two tertiary cutaneous-lymphoma outpatient clinics. <h3>Participants:</h3> Fourteen patients with low-grade PCBCL manifesting with erythematous patches, diagnosed and managed between January 2000 and December 2019. <h3>Intervention:</h3> Clinical data were collected from the medical files. Biopsy specimens of the macules, and if present of the typical nodular/tumoral lesions, were reviewed. <h3>Main outcome measures:</h3> Characterizing the macular lesions of low-grade PCBCL. <h3>Results:</h3> There were 14 patients, aged 16–67 years, 8 had PCFCL and 6 had primary cutaneous marginal zone lymphoma (PCMZL). All had erythematous macules, measuring 1–15 cm, which mimicked: figurate erythema, interstitial granuloma annulare, livedo reticularis, vascular tumors, and in 7 patients showed also follicular accentuation, thus simulated early-stage folliculotropic mycosis fungoides. In 3 patients macules were the presenting lesions, in 2 as the sole manifestation, whereas in 12 patients typical PCBCL lesions were observed during the disease course. On histopathology, the macular lesions showed in all superficial and deep perivascular infiltrates and in all but 1 also periadnexal lymphoid infiltrates. Microdules were observed in 11 biopsy specimens, in only 4 of them nodular infiltrates were also observed B-cells comprised the majority of the lymphocytes in only 4 patients, while in the remaining 10, B and T-cells were either equally distributed or T-cells outnumbered B. Polymerase-based analysis of a patch showed immunoglobulin heavy chain monoclonality in 7 of 11 cases tested. <h3>Conclusions and relevance:</h3> PCMZL and not only PCFCL, as previously reported, may manifest with erythematous macules, rarely as the sole presentation, and more often in conjunction with typical lesions. Histopathologically, the macules are characterized by distinct perivascular-periadnexal and micronodule pattern, and in most of the cases without the nodule formation classically observed in such lymphomas. Physicians should be aware of this unique variant representing a pitfall in the clinical and histopathologic diagnosis of low-grade PCBCL.

Scleromyxedema.

Scleromyxedema is a rare, cutaneous deposition disorder from the group of mucinoses, which can affect multiple organs and is virtually always associated with a monoclonal gammopathy. Cutaneous manifestations are usually generalized, 2 to 3mm sized, dome-shaped or flat-topped, waxy, slightly red to skin-colored papules and sclerodermoid indurations. Neurological, rheumatological, cardiovascular, gastrointestinal, respiratory tract, renal and ophthalmologic manifestations can occur, with decreasing frequency. A serious and potentially lethal complication is the dermato-neuro syndrome which manifests with flu-like prodromes followed by fever, convulsions and coma. Untreated, scleromyxedema usually takes an unpredictable and potentially lethal progressive disease course over several years. According to a widely acknowledged classification by Rongioletti a diagnosis of scleromyxedema can be rendered when (1) generalized, papular and sclerodermoid eruption, (2) a histological triad of mucin deposition, fibroblast proliferation and fibrosis, and (3) monoclonal gammopathy are present, and (4) thyroid disease is absent. Apart from the classic microscopic triad, an interstitial granuloma annulare like pattern was also described. The pathogenesis of scleromyxedema is unknown. A potential role for various, as yet unknown serum factors has been discussed. An unequivocal causal relationship between paraproteinemia and disease manifestations could not be established to date. High dose intravenous immunoglobulins (IVIg) are the first-line treatment of choice according to the most recent European guidelines.

Reactive granulomatous dermatitis as a histological pattern including manifestations of interstitial granulomatous dermatitis and palisaded neutrophilic and granulomatous dermatitis: a study of 52 patients

Confusion exists regarding interstitial granulomatous dermatitis (IGD) and palisaded neutrophilic and granulomatous dermatitis (PNGD). To determine whether IGD and PNGD are two different entities, or whether they must be considered as two subtypes of the same reactive pattern, and thus whether the unification of the nomenclature is necessary. Observational retrospective multicentre study of patients with IGD and PNGD evaluated between 1999 and 2019 and review of their clinical and histological features. We identified 52 patients (38 women and 14 men). Clinical and histological findings of IGD were observed in 88.4% of cases. The most common cutaneous lesions were plaques/macules (IGD) or annular plaques and papules/nodules (PNGD), located mostly on the limbs and trunk. The rope sign was developed in two patients with IGD that associated autoimmune disorders. Similar associated comorbidities (75%) were found in both entities, mainly autoimmune diseases (53.8%). In IGD, the infiltrate was predominantly lympho-histiocytic. Neutrophilic infiltrates, karyorrhexis and skin lesions with limited clinical course were mainly associated with PNGD biopsies. In biopsies with a limited recurrent course, a predominant lymphocytic inflammatory infiltrate was found. Collagen degeneration was present in 75.9% of cases. The floating sign was observed only in IGD type patients (63%). Overlapping histological findings were found in one fourth of cases, especially between IGD and interstitial granuloma annulare. Interface dermatitis, apparently unrelated to drug intake, was observed in 4 cases of IGD. We support the term reactive granulomatous dermatitis to unify both the clinical and histological findings of IGD and PNGD, and the overlapping between IGD and interstitial granuloma annulare. According to this, a spectrum of histological changes will be found depending on the clinical course of the skin lesions.

Annulare With Tuberculosis and Cutis Laxa: A Rare Case Report

Introduction: Granuloma annulare (GA) is a benign, noninfectious granulomatous disorder of unknown etiology, characterized by an annular arrangement of erythematous small nodules and plaques, classically localized on dorsal surfaces of the hands and feet. GA shows palisading granulomas with a central zone of necrobiotic collagen and mucin deposition surrounded by a palisade of histiocytes. Here, we reported a 24-year-old man with GA combined with tuberculosis and cutis laxa. Case presentation: A 24-year-old man was presented with skin annular lesions on the trunk and extremities without subjective symptoms for three years. The annular lesions first arose in the trunk that slowly progressed to most parts of the body and cutis laxa-like lesions appeared on the left inguinal region with inguinal hernia two years ago. At the same time, the patient was diagnosed with pulmonary tuberculosis due to the hemoptysis for two years and the sputum culture for tuberculosis bacillus was positive. He was treated with triple anti-tuberculosis drugs regularly. Partial remission of the skin lesions was noted since then. Pathological examination showed similar histological changes in the interstitial pattern of GA. Discussion: Tuberculosis was a possible etiologic factor in GA because of the coincidental occurrence, granulomatous histologic features, and positive tuberculin skin tests. In fact, some cases of GA with chronic pulmonary tuberculosis responding to a specific anti-tuberculosis therapy were reported. It is worth noting that tuberculids, generalized exanthems in the skin of tuberculous patients possibly resulting from hypersensitivity reactions to the tubercle bacillus, may mimic GA. Furthermore, our patient also showed extremely characteristic slack skin in posterior lumbar and groin, which was deemed to be related to reduction and destruction of elastic fibers. Conclusion: Generalized interstitial GA with tuberculosis and cutis laxa is vary rare, which is worth being aware of the possibility of such a occurrence.

The interstitial variant of granuloma annulare: Clinicopathologic study of 69 cases with a comparison with conventional granuloma annulare

The full-blown lesion of granuloma annulare (GA) is characterized by necrobiotic granulomas with palisading of histiocytes and stromal mucin deposition. Cases in which the granulomatous features are not fully developed have been described as the "interstitial" variant; however, there is no good definition regarding their criteria for diagnosis. We conducted a retrospective study of 97 cases of GA. Cases of interstitial GA (69) were paucicellular with scant to no mucin, with only a few scattered mononuclear cells but lacking well-formed granulomas with multinucleated giant cells. Immunohistochemical study showed that the cells in conventional cases of GA stained strongly positive for CD68 and CD163, whereas the small mononuclear cells in interstitial GA were strongly positive only for CD163. Interstitial GA differs from the classical GA in several respects, including morphology and immunophenotype. Use of antibodies to CD163 may be helpful for distinguishing the interstitial variant from other conditions. Recognition of the interstitial variant is of importance to explain the presence of lesions that clinically are suspicious for GA but histologically do not resemble the conventional form of the disease.

Concomitant lichen sclerosus and interstitial granuloma annulare in a 56-year-old female with suspected autoimmune disease

Concomitant lichen sclerosus and interstitial granuloma annulare in a 56-year-old female with suspected autoimmune disease

Interstitial Mycosis Fungoides: A Clinicopathologic Study of 21 Patients.

Interstitial mycosis fungoides (IMF) is a rare histopathologic variant of mycosis fungoides (MF) that may mimic other inflammatory dermatoses, mainly interstitial granuloma annulare, inflammatory morphea, and interstitial granulomatous dermatitis. Only small series and sporadic case reports of IMF have been described in the literature. We reviewed 27 specimens from 21 patients with IMF (M:F=11:10, median age 60) to better characterize clinical, histopathologic, and immunohistochemical features of this disease. Most patients presented clinically with patches and/or plaques. Conventional MF was documented before, concomitant with, or after IMF in 12 patients, whereas only in 2 patients different biopsies showed exclusive features of IMF over a period of 4 and 191 months, respectively. Histology revealed in all cases variably long, linear aggregates of dermal lymphocytes splaying the collagen fibers, involving predominantly the superficial and mid-dermis (6 cases) or the entire dermis (21 cases). Immunohistochemical stainings revealed a cytotoxic phenotype in 9/18 tested cases. Variable amounts of histiocytes/macrophages were found interstitially in all tested biopsies but never represented a population larger than that of T lymphocytes. Our study shows that IMF is a peculiar variant of MF with frequent cytotoxic phenotype. This histopathologic variant in most cases represents a transient pattern in otherwise conventional MF. Accurate clinicopathologic correlation and phenotypic studies of atypical dermal interstitial lymphohistiocytic infiltrates allow to make a correct diagnosis.

Interstitial Granulomatous Dermatitis Associated with Rheumatoid Arthritis.

Dear Editor: Interstitial granulomatous dermatitis (IGD) is a rare and peculiar disorder with cutaneous and joint manifestations1. IGD may be associated with rheumatologic and hematologic disorders of underlying malignancies2,3. Herein, we report a case of IGD associated with rheumatoid arthritis (RA). A 59-year-old Korean woman presented with multiple erythematous plaques on both extremities for 10 days (Fig. 1A). Upon physical examination, the plaques were linear shaped, non-tender, and palpable. She had been diagnosed with RA 17 years earlier. She had taken prednisolone, nonsteroidal anti-inflammatory drugs, and methotrexate to treat RA for 7 years. One month earlier, her arthritis symptoms had stabilized and the rheumatologist withdrew methotrexate. Laboratory test findings were non-specific except for an elevated C-reactive protein (CRP) level (7.12 mg/dl; normal range, 0.01~0.47 mg/dl) and erythrocyte sedimentation rate (ESR) (81 mm/h; normal range, 0~15 mm/h). Histopathologic findings indicated perivascular and interstitial lymphohistiocytic infiltration through the dermis and chronic granulomatous inflammation with collagen degeneration in the upper dermis. Immunohistochemically, most of the infiltrating inflammatory cells were CD 68-positive. Alcian blue staining revealed no mucin deposition in the areas of granulomatous inflammation (Fig. 2). Based on clinical and histological findings, she was diagnosed with IGD. A 7.5-mg methotrexate dose was given weekly and the daily prednisolone dose was increased from 5 mg to 15 mg. A topical 0.1% tacrolimus ointment and methylprednisolone cream were also applied daily for 2 months. The lesions were nearly cleared and ESR and CRP were found to be within normal limits after 2-month follow-up (Fig. 1B). Fig. 1 (A) Multiple, erythematous, palpable, and linear shaped plaques on both extremities. (B) Nearly clearing of lesions after a 2-month follow-up. Fig. 2 (A) A perivascular and interstitial lymphohistiocyte infiltration in the entire dermis (HE B: ×100, C: ×400). ... The most common clinical findings of IGD are asymptomatic multiple papules and plaques (70%~90% of cases)2. The rope sign was named for the linear prominent cutaneous cord-like lesions, considered pathognomic for IGD1. However, these lesions are not an essential feature, and are reported in only 9% of cases3. The histopathologic findings show interstitial CD 68-positive histiocyte infiltration around focally degenerated collagen2,4. Epidermal changes, mucin deposition, neutrophil and/or eosinophil infiltration, and vasculitis are usually absent 2. Differential diagnoses include interstitial granuloma annulare (IGA), interstitial granulomatous drug reaction (IGDR), and palisaded neutrophilic and granulomatous dermatitis (PNGD)1,2,4. In IGA, prominent mucin deposition and only focal interstitial infiltration could be found. Recent change of medication is present in IGDR, and IGDR presents with basal cell vacuolization and lichenoid changes with eosinophils2. Leukocytoclastic vasculitis and pandermal infiltration of neutrophil frequently present in early lesion of PNGD, and palisading granulomatous inflammation is the typical feature of fully developed one1. The pathogenesis of IGD may be associated with immune complex deposition caused by immune reactants of systemic inflammatory diseases5. Interestingly, IGD lesions in our case began to occur in association with the flare-up of RA after methotrexate withdrawal, although the causal relationship remains unknown. From our case we suggest that IGD should be considered among the differential diagnoses for patients with rheumatologic disease and cord-like skin lesions.

GRANULOMA ANULAR INTERSTICIAL DISSEMINADO

Relatamos um caso clínico-patológico de uma paciente de 62 anos com diagnóstico de granuloma anular intersticial, cujas lesões possuíam aspecto de pápulas agrupadas, sem atrofia central, distribuídas em membros inferiores, nádegas e dorso. O estudo histopatológico foi fundamental para conclusão diagnóstica uma vez que na avaliação inicial essa doença não estava entre as hipóteses iniciais.

Evolution of granuloma annulare to mid‐dermal elastolysis: report of a case and review of the literature

A 55-year-old healthy Caucasian female, on no medication, was seen by a dermatologist because of a patchy, slightly indurated and violaceous eruption involving her neck and trunk. The clinical impression was of granuloma annulare (GA). Over a period of several months the violaceous lesions became atrophic with loss of colour and eventual wrinkling of lesional skin. Sequential skin biopsies were obtained, which revealed a spectrum of changes. Those from early violaceous lesional zones displayed perivascular lymphocytic infiltrates and interstitial granulomatous inflammation, characteristic of interstitial GA. Samples from atrophic lesional areas appeared normal on routine sections but an Orcein-Giemsa (OG) stain, prompted by the clinical history of atrophy, revealed absence of elastic fibers in the mid-reticular dermis. The combined clinicopathologic findings pointed to development of mid-dermal elastolysis (MDE) at involutional sites of GA. Owing to consideration of a cutaneous T-cell lymphoma in the differential diagnosis, genotyping in search of T-cell monoclonality was performed and yielded a negative result. Our case supports the existing but scant evidence in the literature that the rare, enigmatic condition termed MDE is an end-result of inflammatory destruction of dermal elastic fibers. GA is one form of dermatitis capable of culminating in this entity, but others have also been implicated.

Solid Variant of Angiomatoid Fibrous Histiocytoma Masked by Interstitial Granuloma Annulare in a 13-year-old Child: No Evidence for Translocation Breakpoints

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Hepatitis C Virus Treatment With Pegylated Interferon-Alfa Therapy Leading to Generalized Interstitial Granuloma Annulare and Review of the Literature

We discuss the diagnosis and management of a case of generalized granuloma annulare (GA) occurring in a 49-year-old man when being treated with pegylated interferon-alfa for hepatitis C infection. In our case, the GA lesions remained despite an undetectable hepatitis C viral load. The GA resolved only with treatment cessation.

Granuloma Annulare

Granuloma annulare is a benign, usually self-limited granulomatous disease of the dermis and subcutaneous tissue. Several distinct subtypes have been recognized, namely localized granuloma annulare, generalized or disseminated granuloma annulare, subcutaneous granuloma annulare, papular granuloma annulare, interstitial or patch granuloma annulare, and perforating granuloma annulare. Localized granuloma annulare is the most common form in children and comprises 75% of cases. Clinically, the condition is characterized by asymptomatic, flesh-colored or erythematous-brown papules, frequently arranged in a ring or annular pattern on the distal extremities. It is estimated that 0.1 to 0.4% of new patients attending dermatologic clinics have granuloma annulare. Most cases of granuloma annulare occur before the age of 30 years. A delayed hypersensitivity and cell-mediated immune response to an antigen contributes to the pathogenesis. Histologic examination of the lesion shows central collagen degeneration and mucin deposition surrounded peripherally by palisading histiocytes and inflammatory cells. Most cases of granuloma annulare are asymptomatic and self-limited; and reassurance is often sufficient. Treatment is mainly for cosmetic purposes and various modalities of treatment options are discussed.

Localized interstitial granuloma annulare induced by subcutaneous injections for desensitization

We describe a patient with interstitial granuloma annulare associated with subcutaneous injection therapy (SIT) for desensitization to a type I allergy. Asymptomatic, erythematous, violaceous annular patches were located at the injection sites on both her arms. Medical history revealed perennial rhinoconjonctivitis treated with SIT (Phostal Stallergen® cat 100% and D. pteronyssinus/D.farinae 50%:50%).

Coexistence of Patch Stage Mycosis Fungoides and Interstitial Granuloma Annulare in the Same Patient

Several clinical and histopathologic variants of mycosis fungoides (MF) have been well described, including the often elusive interstitial MF. Differentiation from other inflammatory disorders, such as interstitial granuloma annulare (GA) and inflammatory morphea, may be extremely difficult. We report a case of MF and GA coexisting in a 54-year-old woman who initially presented to clinic in 2000 with slightly scaly patches on the trunk and extremities, histopathologically diagnostic of MF. A second biopsy taken a few months later revealed an interstitial infiltrate that was initially interpreted as interstitial MF. Over the following 10 years, additional biopsies revealed features of conventional MF. In 2009, a new biopsy showed unequivocal features of interstitial GA. Reevaluation of the original biopsy, diagnostic of "interstitial MF," revealed that this, too, could be better classified as interstitial GA than interstitial MF. Our case illustrates that MF and interstitial GA may coexist simultaneously, thus representing a pitfall in the histopathologic diagnosis of MF. Given the similarities in clinicopathologic presentation, dermatologists and dermatopathologists should be cautious not to inadvertently misinterpret GA as interstitial MF.

An Unusual Histologic Variant of Necrobiotic Xanthogranuloma

Necrobiotic xanthogranuloma (NXG) usually shows a stereotypical histopathologic presentation. However, few unusual cases have been published. We present a patient with NXG showing exceptional histopathologic features. NXG in our patient presents with exclusively dermal granulomatous inflammation mimicking interstitial granuloma annulare. Not only subcutaneous involvement, but also, evident zones of degenerated collagen, foam cells, and cholesterol clefts were missing. Moreover, the case shows overlaps with recently published granulomatous scleromyxedema. Some common clinical and histopathologic features of NXG and scleromyxedema might be based on shared underlying paraproteinemia.

Interstitial granuloma annulare after treatment with pegylated interferon-alfa and ribavirin in a patient with hepatitis C virus infection

Interstitial granuloma annulare after treatment with pegylated interferon-alfa and ribavirin in a patient with hepatitis C virus infection

Secondary syphilis with an interstitial granuloma annulare-like histopathologic pattern

A granulomatous tissue response may be observed in untreated, long-standing lesions of secondary syphilis. In addition to poorly defined granulomatous inflammation, leprosy-like sarcoidal and palisaded granulomatous inflammation has been documented in literature reports of lues. Herein, we report a 47-year-old man who presented with a 3-month history of a generalized non-pruritic macular and papular rash located on the trunk and extremities. Histopathologically, there was an interstitial arrangement of histiocytes with occasional multinucleated giant cells positioned among collagen bundles without associated necrosis, thereby closely mimicking interstitial granuloma annulare. A clue to the diagnosis was the presence of admixed plasma cells. To the best of our knowledge, this is the first reported case of secondary syphilis showing an interstitial granulomatous pattern mimicking interstitial granuloma annulare.