Image Quiz

Enlarging Painless Mass in a Four-Year-Old Girl (continued)

Answer: Subcutaneous granuloma annulare.


Fig. 1-A
Fig. 1-B		 Axial (Fig. 1-A) and coronal (Fig. 1-B) T1-weighted magnetic resonance images showing a lesion (arrows) that is isointense to muscle in the pretibial area within the subcutaneous fat extending to the skin. There is no osseous involvement.

For larger view, click on image

Fig. 2-A
Fig. 2-B		 Axial (Fig. 2-A) and coronal (Fig. 2-B) short tau inversion recovery (STIR) magnetic resonance images demonstrating a subcutaneous pretibial lesion (arrows) with a hyperintense signal adjacent to, but not involving, the tibia. (STIR images are similar to fat-saturated T2-weighted images but have more uniform fat-saturation.)

For larger view, click on image

Fig. 3-A
Fig. 3-B		 Fig. 3-A Low-power histologic section illustrating the area of necrosis (star) surrounded by fibroblasts and inflammatory cells (arrow) (periodic acid-Schiff stain; original magnification, ×4).
Fig. 3-B Higher power histological section showing central bland dystrophic necrosis (star) surrounded by palisading epithelioid cells (arrow) (periodic acid-Schiff stain; original magnification, ×10).

For larger view, click on image

Clinical Course

Following excision of the large lesion, there has been no recurrence noted as of the time of this writing. The satellite lesions regressed over the next few months and, by six months after the diagnosis, had disappeared.

Discussion

Subcutaneous granuloma annulare is an uncommon, benign, inflammatory disorder that occurs in children and that is characterized by deep dermal or subcutaneous nodules. Patients typically present between the ages of two and six years with a several-month history of firm, nontender, soft-tissue nodules. The most common sites of involvement are the pretibial area, other lower-extremity locations, the forearm, the forehead, and the scalp1-5. A slight female predominance has been reported2,5. Typical subcutaneous granuloma annulare lesions are single or multiple small nodules in the deep subcutaneous tissue2,3. These nodules are typically mobile but can be immobile if they adhere tightly to the underlying fascia.

The etiology of subcutaneous granuloma annulare is unknown. While trauma has been suggested as a cause of these lesions, one study reported a low rate of trauma history in these patients5. Subcutaneous granuloma annulare is a subtype of nodular granuloma annulare disorders, which also include localized, generalized, and perforating subtypes1. Granuloma annulare and rheumatoid-like nodules in adults have been associated with systemic connective-tissue diseases, such as rheumatoid arthritis, but subcutaneous granuloma annulare in children appears to be an isolated disease2,3. The literature lists several synonyms for subcutaneous granuloma annulare, including deep granuloma annulare, pseudorheumatoid nodule, subcutaneous palisading granuloma, and necrobiotic granuloma2,3,6.

Plain radiographs and magnetic resonance images can assist in narrowing the differential diagnosis of a subcutaneous mass. Radiographically, subcutaneous granuloma annulare presents as a nonspecific soft-tissue mass without osseous involvement or calcification3,5,6. Magnetic resonance imaging of subcutaneous granuloma annulare lesions confirms that the nodules are localized to the subcutaneous tissues extending to the fascia but not penetrating the deeper structures or adjacent compartments7,8. The lesions are heterogeneous and have indistinct or infiltrating margins due to the poorly circumscribed inflammatory response5,7. The nodules are isointense or slightly hyperintense to muscle on T1-weighted images (Fig. 1-A and 1-B)7. T2-weighted images show high signal intensity with surrounding edema in some cases (Fig. 2-A and 2-B)7-9. Contrast enhancement has been reported to be minimally heterogeneous to homogeneous, probably reflecting the inflammatory nature and increased vascularity in these lesions7,8. On computed tomographic scans, the lesions have a homogeneous attenuation similar to that of muscle and most often do not enhance10.

The differential diagnosis of subcutaneous nodules in the extremities includes trauma, infection, soft-tissue neoplasm, metabolic bone disease, skin disease, and inflammatory or autoimmune disorders3. Laboratory tests, such as those used to evaluate the complete blood count, the erythrocyte sedimentation rate, and the presence of antinuclear antibodies or rheumatoid factor, help exclude other possible causes of the nodules, as these tests reveal normal results in patients with subcutaneous granuloma annulare3,5,6,11. Atypical symptoms, such as pain, rapidly enlarging nodules, or nodules in atypical locations, along with the relative rarity of subcutaneous granuloma annulare may make initial diagnosis difficult7. While a complete history and physical examination in a typical patient often suggests the correct diagnosis, biopsy of the lesion (incisional or excisional), along with clinical correlation, is required for definitive diagnosis5,11.

Histologically, subcutaneous granuloma annulare in the deep dermis or subcutaneous layers contains three zones: (a) a central zone of fibrinoid degeneration of collagen and necrosis (necrobiosis), (b) a surrounding zone of palisading histiocytes, and (c) a peripheral zone of mononuclear inflammatory cells, fibroblasts, and eosinophils (Fig. 3-A and 3-B)2-6,12. The presence of mitotic figures varies between regions of the lesion, but most are usually present in the palisading region. A few multinucleated giant cells may be found, but this is not a typical finding in subcutaneous granuloma annulare5. Vascular proliferation is a common histologic finding at the periphery of the lesions4,5,12. Periodic acid-Schiff-positive material is present within the central foci of fibrinoid necrosis (Fig. 3-B)12.

While subcutaneous granuloma annulare and rheumatoid arthritis nodules are indistinguishable histologically, the clinical and laboratory findings for these entities differ substantially. Rheumatoid arthritis is almost always associated with high serum titers of rheumatoid factor, the presence of joint disease, and bone erosions, whereas subcutaneous granuloma annulare is not associated with these findings1,11. Additionally, subcutaneous granuloma annulare is not associated with generalized connective-tissue disorders or rheumatologic disorders such as rheumatoid arthritis2,6.

Since spontaneous resolution often occurs, complete excision of the lesions is not required for definitive treatment. Importantly, the risk of recurrence of the nodules ranges from 19% to 75% and recurrence can occur several months to years after excision2,3,5,13. Many pharmacologic treatments, such as corticosteroids, potassium iodide, dapsone, niacinamide (nicotinamide), chlorambucil, and isotretinoin, have been used experimentally for treatment without evidence of efficacy3,14.

In an otherwise healthy child who presents with a rapidly growing nontender subcutaneous soft-tissue mass or masses without radiographic evidence of osseous involvement or calcification, subcutaneous granuloma annulare must be included in the differential diagnosis.

*In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from Stryker (which sponsors the Research Fellowship of one of the authors). Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

References

1. Barron DF, Cootauco MH, Cohen BA. Granuloma annulare. A clinical review. Lippincotts Prim Care Pract. 1997;1:33-9.
2. Grogg KL, Nascimento AG. Subcutaneous granuloma annulare in childhood: clinicopathologic features in 34 cases. Pediatrics. 2001;107:E42.
3. Felner EI, Steinberg JB, Weinberg AG. Subcutaneous granuloma annulare: a review of 47 cases. Pediatrics. 1997;100:965-7.
4. Patterson JW. Rheumatoid nodule and subcutaneous granuloma annulare. A comparative histologic study. Am J Dermatopathol. 1988;10:1-8.
5. McDermott MB, Lind AC, Marley EF, Dehner LP. Deep granuloma annulare (pseudorheumatoid nodule) in children: clinicopathologic study of 35 cases. Pediatr Dev Pathol. 1998;1:300-8.
6. Trobs RB, Borte M, Voppmann A, Weidenbach H, Thiele J. Granuloma annulare, nodular type--a subcutaneous pseudorheumatoid lesion in children. Eur J Pediatr Surg. 1997;7:349-52.
7. Chung S, Frush DP, Prose NS, Shea CR, Laor T, Bisset GS. Subcutaneous granuloma annulare: MR imaging features in six children and literature review. Radiology. 1999;210:845-9.
8. Vandevenne JE, Colpaert CG, De Schepper AM. Subcutaneous granuloma annulare: MR imaging and literature review. Eur Radiol. 1998;8:1363-5.
9. Shehan JM, El-Azhary RA. Magnetic resonance imaging features of subcutaneous granuloma annulare. Pediatr Dermatol. 2005;22:377-8.
10. Argent JD, Fairhurst JJ, Clarke NM. Subcutaneous granuloma annulare: four cases and review of the literature. Pediatr Radiol. 1994;24:527-9.
11. Gurer G, Faruk Sendur O, Tasci Bozbas G. Benign rheumatoid nodules in childhood. Pediatr Int. 2006;48:94-6.
12. Charles CR, Johnson BL, Damm SR. Granuloma annulare. Int J Dermatol. 1976;15:655-65.
13. Patrizi A, Neri I, Guerrini V, Marini R, Fiorillo L. Granuloma annulare: clinical and laboratory findings in a pediatric group of patients. Acta Derm Venereol. 1996;76-4:326-8.
14. Smith MD, Downie JB, DiCostanzo D. Granuloma annulare. Int J Dermatol. 1997;36:326-33.