Cover Quizlet
The sarcoidal variant of annular elastolytic granuloma Jacqueline G. Berliner MD1 , Anna Haemel MD1 , Philip E. LeBoit MD1,2 and Laura B. Pincus MD1,2 1
Department of Dermatology, University of California San Francisco, 2 Department of Pathology, University of California San Francisco, e-mail: [email protected]
Keywords: annular elastolytic granuloma, actinic granuloma, granulomatous dermatitis, sarcoid Accepted for publication September 10, 2013
A 59-year-old woman who was otherwise healthy presented for evaluation of an annular plaque on the left forehead. The plaque had an erythematous scaly raised border, and the central portion was hypopigmented and subtly atrophic (Figures 1 and 3). The plaque was solitary, as a full body examination did not reveal additional cutaneous lesions. It was asymptomatic and longstanding but had been slowly expanding. A biopsy of the plaque had been previously performed in 2004, at which time the patient was under the care of a different clinical team. At the time, scant clinical information was included with the specimen. The 2004 biopsy showed tightly packed nodular collections of histiocytes and was interpreted as probably representing sarcoidosis. Subsequent systemic evaluation for sarcoidosis, including a chest x-ray and an angiotensin converting enzyme (ACE) level, was negative. The patient recently presented to our institution, where our clinicians were unable to reconcile the histopathology with the clinical presentation. Therefore, an additional biopsy was performed. The biopsy showed dense small and large compact sarcoidal aggregations of histiocytes distributed in a vaguely band-like configuration in the upper dermis (Figures 2 and 4). The aggregations were accompanied by small lymphocytes (Figures 4 and 5). A diagnosis of sarcoidal granulomatous dermatitis was rendered, and a differential diagnosis that included sarcoidosis, infection, granulomatous rosacea, and a cutaneous manifestation of Crohn’s disease was offered. Special stains (Fite, PAS-D, and Brown-Brenn) were performed and failed to reveal organisms (mycobacteria, fungi and bacteria,
918
Fig. 1. Frontal view displaying an annular plaque with an erythematous raised border and central subtle atrophy with hypopigmentation.
respectively). Granulomatous rosacea was the least favored diagnosis, since the granulomas were not perifollicular. Our clinicians subsequently provided a clinical photograph, which the dermatopathology group considered to be compelling for annular elastolytic granuloma (AEG), and thus a sarcoidal variant of AEG was favored as the best diagnosis for the case. An elastic von Gieson (EVG) stain was then performed and revealed loss of elastic tissue throughout the dermis, including areas outside the sarcoidal granulomas (Figure 6). Of note, an ACE level was re-evaluated at that time and again was negative. Additional pulmonary evaluation was deferred due to lack of symptoms. AEG is a granulomatous skin disease characterized by annular plaques typically occurring on sun-exposed skin. Each plaque classically has an elevated rim and central pallor, atrophy, or depression,
Cover Quizlet
Fig. 2. A scanning magnification view demonstrates sarcoidal granulomas in a band-like distribution within the upper dermis.
as is exemplified by the patient presented herein.1 Over the past several decades, there has been significant debate surrounding the nosology, spectrum of disease, etiology, and defining histopathologic features of AEG. This condition is commonly referred to as actinic granuloma, which reflects the hypothesis that actinic radiation induces damage to the elastic tissue, which then functions as an autoimmune target or antigen.2 The term annular elastolytic giant cell granuloma (AEGCG) was put forth by those who did not favor a causal relationship with sun exposure.1 We prefer AEG as a less redundant alternative to AEGCG. Other conditions such as necrobiosis lipoidica of the face and scalp, Miescher’s granuloma of the face, and granuloma multiforme fall in the same spectrum of disease and possibly represent the same condition.3 The literature regarding whether a sarcoidal pattern of granulomatous inflammation can represent the histopathology of AEG is inconsistent. In early descriptions, it is mentioned that occasionally the granulomatous infiltrate of AEG can assume a sarcoidal pattern in patients without systemic sarcoidosis.2,4,5 However, one early report explicitly distinguishes AEG from sarcoid by the presence tightly packed granulomas, thereby implying that such granulomas are not a feature of AEG.1 The case presented herein demonstrates that a sarcoidal pattern of granulomatous inflammation can be a manifestation of AEG. Some authorities contend that AEG is a variant of granuloma annulare (GA), and, indeed, there are many overlapping features. For example, clinically, annular plaques characterize both conditions. Microscopically, both conditions are characterized by palisading or interstitial granulomatous dermatitis;
the presence of mucin is more common in GA, while elastolysis and elastophagocytosis are more common in AEG. In some patients, lesions with the typical histopathology of GA present within sunprotected sites, while sun-damaged skin shows the findings of AEG. Also, elastolysis can be seen in association with any granulomatous infiltrate, especially when occurring in skin heavily altered by solar elastosis, and thus its presence alone is not specific.6 Nonetheless, some argue that the degree of elastolysis is significantly increased in AEG, suggesting that the damaged elastic fibers trigger a granulomatous inflammatory response.3 Frequently, multinucleated histiocytes represent a component of the infiltrate, and these cells contain elastic tissue fibers in their cytoplasm. In the most developed cases, the area lacking elastotic fibers that is bordered by histiocytes (but not infiltrated by them) is also fibrotic. The relationship between AEG and sarcoidosis also is complex. For example, a clinical presentation similar to AEG has been described in patients with systemic sarcoidosis. Such patients are probably best classified as having an annular variant of cutaneous sarcoidosis.7 However, lesions that are clinically and histopathologically compatible with AEG, without a sarcoidal pattern of inflammation, have been described in patients with systemic sarcoidosis.1 These patients likely reflect occasional clinical and histopathologic overlap that can be seen in patients with non-infectious granulomatous dermatitides, such as GA, AEG and sarcoidosis. While the pattern of granulomatous inflammation in AEG is typically palisaded or interstitial, we posit that it can rarely consist of tightly packed nodular aggregates of histiocytes in a sarcoidal pattern, as seen in this case. Therefore, if there is a compelling clinical presentation for AEG, with a sarcoidal pattern of granulomatous inflammation seen microscopically, AEG probably represents the best diagnostic pigeonhole. As this case illustrates, sometimes a picture can say a thousand words. Fig. 3. A lateral view of the annular plaque highlights scale overlying its erythematous raised border. Fig. 4. At medium magnification, large and small collections of epitheloid histiocytes form tight sardoidal granulomas in a band-like distribution
919
Cover Quizlet within the papillary dermis. There are also admixed lymphocytes. Fig. 5. High magnification demonstrates small collections of epitheloid histiocytes forming a sarcoidal granuloma.
Fig. 6. An elastic tissue stain demonstrates loss of elastic tissue throughout most of the reticular dermis extending to the depth of the arrow. Intact elastic tissue fibers are present subjacent to the arrow.
References 1. Hanke CW, Bailin PL, Roenigk HH,Jr. Annular elastolytic giant cell granuloma. A clinicopathologic study of five cases and a review of similar entities. J Am Acad Dermatol 1979; 1: 413. 2. O’Brien JP, Regan W. Actinically degenerate elastic tissue is the likely antigenic basis of actinic granuloma of the skin and of temporal arteritis. J Am Acad Dermatol 1999; 40: 214.
920
3. Steffen C. Actinic granuloma (O’brien). J Cutan Pathol 1988; 15: 66. 4. O’Brien JP. Actinic granuloma. an annular connective tissue disorder affecting sun- and heat-damaged (elastotic) skin. Arch Dermatol 1975; 111: 460. 5. O’Brien JP. Actinic granuloma: The expanding significance. an analysis of its origin in elastotic (‘‘aging”) skin and a definition of necrobiotic
(vascular), histiocytic, and sarcoid variants. Int J Dermatol 1985; 24: 473. 6. Ragaz A, Ackerman AB. Is actinic granuloma a specific condition? Am J Dermatopathol 1979 Spring; 1: 43. 7. Gambichler T, Herde M, Hoffmann K, Stucker M, Altmeyer P, Jansen T. Sarcoid variant of actinic granuloma: Is it annular sarcoidosis? Dermatology 2001; 203: 353.
The sarcoidal variant of annular elastolytic granuloma Jacqueline G. Berliner MD1 , Anna Haemel MD1 , Philip E. LeBoit MD1,2 and Laura B. Pincus MD1,2 1
Department of Dermatology, University of California San Francisco, 2 Department of Pathology, University of California San Francisco, e-mail: [email protected]
Keywords: annular elastolytic granuloma, actinic granuloma, granulomatous dermatitis, sarcoid Accepted for publication September 10, 2013
A 59-year-old woman who was otherwise healthy presented for evaluation of an annular plaque on the left forehead. The plaque had an erythematous scaly raised border, and the central portion was hypopigmented and subtly atrophic (Figures 1 and 3). The plaque was solitary, as a full body examination did not reveal additional cutaneous lesions. It was asymptomatic and longstanding but had been slowly expanding. A biopsy of the plaque had been previously performed in 2004, at which time the patient was under the care of a different clinical team. At the time, scant clinical information was included with the specimen. The 2004 biopsy showed tightly packed nodular collections of histiocytes and was interpreted as probably representing sarcoidosis. Subsequent systemic evaluation for sarcoidosis, including a chest x-ray and an angiotensin converting enzyme (ACE) level, was negative. The patient recently presented to our institution, where our clinicians were unable to reconcile the histopathology with the clinical presentation. Therefore, an additional biopsy was performed. The biopsy showed dense small and large compact sarcoidal aggregations of histiocytes distributed in a vaguely band-like configuration in the upper dermis (Figures 2 and 4). The aggregations were accompanied by small lymphocytes (Figures 4 and 5). A diagnosis of sarcoidal granulomatous dermatitis was rendered, and a differential diagnosis that included sarcoidosis, infection, granulomatous rosacea, and a cutaneous manifestation of Crohn’s disease was offered. Special stains (Fite, PAS-D, and Brown-Brenn) were performed and failed to reveal organisms (mycobacteria, fungi and bacteria,
918
Fig. 1. Frontal view displaying an annular plaque with an erythematous raised border and central subtle atrophy with hypopigmentation.
respectively). Granulomatous rosacea was the least favored diagnosis, since the granulomas were not perifollicular. Our clinicians subsequently provided a clinical photograph, which the dermatopathology group considered to be compelling for annular elastolytic granuloma (AEG), and thus a sarcoidal variant of AEG was favored as the best diagnosis for the case. An elastic von Gieson (EVG) stain was then performed and revealed loss of elastic tissue throughout the dermis, including areas outside the sarcoidal granulomas (Figure 6). Of note, an ACE level was re-evaluated at that time and again was negative. Additional pulmonary evaluation was deferred due to lack of symptoms. AEG is a granulomatous skin disease characterized by annular plaques typically occurring on sun-exposed skin. Each plaque classically has an elevated rim and central pallor, atrophy, or depression,
Cover Quizlet
Fig. 2. A scanning magnification view demonstrates sarcoidal granulomas in a band-like distribution within the upper dermis.
as is exemplified by the patient presented herein.1 Over the past several decades, there has been significant debate surrounding the nosology, spectrum of disease, etiology, and defining histopathologic features of AEG. This condition is commonly referred to as actinic granuloma, which reflects the hypothesis that actinic radiation induces damage to the elastic tissue, which then functions as an autoimmune target or antigen.2 The term annular elastolytic giant cell granuloma (AEGCG) was put forth by those who did not favor a causal relationship with sun exposure.1 We prefer AEG as a less redundant alternative to AEGCG. Other conditions such as necrobiosis lipoidica of the face and scalp, Miescher’s granuloma of the face, and granuloma multiforme fall in the same spectrum of disease and possibly represent the same condition.3 The literature regarding whether a sarcoidal pattern of granulomatous inflammation can represent the histopathology of AEG is inconsistent. In early descriptions, it is mentioned that occasionally the granulomatous infiltrate of AEG can assume a sarcoidal pattern in patients without systemic sarcoidosis.2,4,5 However, one early report explicitly distinguishes AEG from sarcoid by the presence tightly packed granulomas, thereby implying that such granulomas are not a feature of AEG.1 The case presented herein demonstrates that a sarcoidal pattern of granulomatous inflammation can be a manifestation of AEG. Some authorities contend that AEG is a variant of granuloma annulare (GA), and, indeed, there are many overlapping features. For example, clinically, annular plaques characterize both conditions. Microscopically, both conditions are characterized by palisading or interstitial granulomatous dermatitis;
the presence of mucin is more common in GA, while elastolysis and elastophagocytosis are more common in AEG. In some patients, lesions with the typical histopathology of GA present within sunprotected sites, while sun-damaged skin shows the findings of AEG. Also, elastolysis can be seen in association with any granulomatous infiltrate, especially when occurring in skin heavily altered by solar elastosis, and thus its presence alone is not specific.6 Nonetheless, some argue that the degree of elastolysis is significantly increased in AEG, suggesting that the damaged elastic fibers trigger a granulomatous inflammatory response.3 Frequently, multinucleated histiocytes represent a component of the infiltrate, and these cells contain elastic tissue fibers in their cytoplasm. In the most developed cases, the area lacking elastotic fibers that is bordered by histiocytes (but not infiltrated by them) is also fibrotic. The relationship between AEG and sarcoidosis also is complex. For example, a clinical presentation similar to AEG has been described in patients with systemic sarcoidosis. Such patients are probably best classified as having an annular variant of cutaneous sarcoidosis.7 However, lesions that are clinically and histopathologically compatible with AEG, without a sarcoidal pattern of inflammation, have been described in patients with systemic sarcoidosis.1 These patients likely reflect occasional clinical and histopathologic overlap that can be seen in patients with non-infectious granulomatous dermatitides, such as GA, AEG and sarcoidosis. While the pattern of granulomatous inflammation in AEG is typically palisaded or interstitial, we posit that it can rarely consist of tightly packed nodular aggregates of histiocytes in a sarcoidal pattern, as seen in this case. Therefore, if there is a compelling clinical presentation for AEG, with a sarcoidal pattern of granulomatous inflammation seen microscopically, AEG probably represents the best diagnostic pigeonhole. As this case illustrates, sometimes a picture can say a thousand words. Fig. 3. A lateral view of the annular plaque highlights scale overlying its erythematous raised border. Fig. 4. At medium magnification, large and small collections of epitheloid histiocytes form tight sardoidal granulomas in a band-like distribution
919
Cover Quizlet within the papillary dermis. There are also admixed lymphocytes. Fig. 5. High magnification demonstrates small collections of epitheloid histiocytes forming a sarcoidal granuloma.
Fig. 6. An elastic tissue stain demonstrates loss of elastic tissue throughout most of the reticular dermis extending to the depth of the arrow. Intact elastic tissue fibers are present subjacent to the arrow.
References 1. Hanke CW, Bailin PL, Roenigk HH,Jr. Annular elastolytic giant cell granuloma. A clinicopathologic study of five cases and a review of similar entities. J Am Acad Dermatol 1979; 1: 413. 2. O’Brien JP, Regan W. Actinically degenerate elastic tissue is the likely antigenic basis of actinic granuloma of the skin and of temporal arteritis. J Am Acad Dermatol 1999; 40: 214.
920
3. Steffen C. Actinic granuloma (O’brien). J Cutan Pathol 1988; 15: 66. 4. O’Brien JP. Actinic granuloma. an annular connective tissue disorder affecting sun- and heat-damaged (elastotic) skin. Arch Dermatol 1975; 111: 460. 5. O’Brien JP. Actinic granuloma: The expanding significance. an analysis of its origin in elastotic (‘‘aging”) skin and a definition of necrobiotic
(vascular), histiocytic, and sarcoid variants. Int J Dermatol 1985; 24: 473. 6. Ragaz A, Ackerman AB. Is actinic granuloma a specific condition? Am J Dermatopathol 1979 Spring; 1: 43. 7. Gambichler T, Herde M, Hoffmann K, Stucker M, Altmeyer P, Jansen T. Sarcoid variant of actinic granuloma: Is it annular sarcoidosis? Dermatology 2001; 203: 353.
