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Subcutaneous Granuloma Annulare in a Child's Palm: A Case Report

Posted on: Sunday, 12 February 2006, 03:03 CST

By Takeyama, Junji; Sanada, Takehiko; Watanabe, Mika; Hatori, Masahito; Et al

We present a rare case of subcutaneous lesions arising in the palm of a 4-year-old girl. Histologic examination of the biopsy specimens showed granulomatous inflammation with focal necrobiosis, which was consistent with subcutaneous granuloma annulare. Subcutaneous granuloma annulare is a self-limited disease and treatment is not required, although recurrence and/or multiple lesions are frequent. (J Hand Surg 2006;31A:103-106. Copyright 2006 by the American Society for Surgery of the Hand.)

Key words: Subcutaneous granuloma annulare, child, palm, histiocyte, immunohistochemistry.

Granuloma annulare (GA) is a benign, usually self-limited granulomatous disease of the dermis and subcutaneous tissue. There are 4 predominant types: localized, generalized, perforating, and subcutaneous.1 The subcutaneous form is characterized by its presence on the extremities and scalp and by its predilection for children.2-7 Histologie features are palisading granuloma with a small focus of necrosis or necrobiosis. Although histologically it resembles a rheumatoid nodule, it has no association with rheumatologic or generalized connective-tissue disorders. Several labels such as subcutaneous granuloma annulare (SGA), deep GA, and pseudorheumatoid nodule have been applied to this lesion.2-7 The etiology of childhood SGA remains unknown although proposed mechanisms and associations are numerous. Trauma appears to be the most probable association with SGA.5,6 We present a case of SGA arising in a 4-year-old girl's palm. Granuloma annulare involving the palm is very rare.8-10 In reviewing the literature we found 1 adult case of the localized form9 and 1 pediatric SGA.10

Case Report

A Japanese girl aged 4 years 8 months was referred for evaluation of 2 painless, enlarging subcutaneous nodules in the left palm that had been present for 4 months (Fig. 1). She was otherwise healthy and had no apparent history of trauma or subcutaneous nodules. Laboratory examination (hemogram and biochemistry) showed no abnormalities. On magnetic resonance imaging both nodules showed low intensity on T1-weighted images and high intensity on T2-weighted images. The nodules were defined poorly, suggesting infiltrative margins. The continuity of the lesions was not apparent. We performed an incisional biopsy procedure for definitive diagnosis. Histologic examination of the 2 lesions yielded the same findings. We observed granulomatous inflammation with foci of necrobiosis in the deep dermis and subcutaneous tissue (Figs. 2A, B). Chronic inflammation with sparse eosinophils was seen in the background. Fragmented elastic fibers were scattered in the cellular aggregates (Fig. 2C). The epidermis became thick with hyperkeratosis. Perivascular, non-specific lymphocytic infiltration was seen in the upper and mid-dermis. Immunohistochemical study showed that the predominant mononuclear cells were positive for the markers of mesenchymal cells (vimentin) and histiocytes (CD68, Clone PGM1). PGM1 showed a relatively restricted reactivity with elements of the monocyte/macrophage lineage. Mitoses were observed scattered in the cellular area (Fig. 2A). Test results for MIB-1, which detects a proliferation-associated nuclear antigen and is often used as a marker of cells with proliferative nature, were positive in approximately 15% of the histiocytic cells. Examination with an electron microscope showed histiocytes containing numerous phagosomes, phagocytosed lipid droplets, and degenerated fibrinoid material (Fig. 3). These findings were consistent with SGA. No bacteria, fungi, or acid-fast bacilli were detected by microscopic examination and tissue culture. The lesions became smaller in size after the biopsy procedure without treatment. At the 6-month follow- up evaluation, however, another nodule appeared close to the surgical scar of the hypothenar eminence, suggesting recurrent lesion. It did not show aggressive growth and showed tendency for resolution but did not completely resolve in the following 3 months.

Figure 1. The lesions are located at the base of the middle finger and the hypothenar eminence of the left hand.

Figure 2. (A) Histologic examination shows infiltration of histiocytes with somewhat epithelioid appearance and scattered lymphocytes. Mitotic figures are observed sporadically (arrows) (hematoxylin-eosin, magnification 400). (B) There are areas of collagen necrosis accompanied by palisading histiocytes (hematoxylin- eosin, magnification 200). (C) Numerous fragmented elastic fibers are seen admixed with the histiocytic infiltration (Elastica-Masson stain, magnification 200).

Discussion

The case reviews of SGA are summarized in Table 1. Subcutaneous granuloma annulare is a disorder mainly in children in which deep dermal or subcutaneous nodules are distributed on the head and extremities. Although SGA often affects the hands and the fingers a case involving the palm is very rare. Grant et al8 reported 7 cases of GA in the hand, all of which affected the dorsal surfaces. In our review of the English literature we found only 2 cases of GA in the palm.9,10 The first report9 described a localized GA arising on the palms of a 40-year-old woman. The second report10 involved a 2-year- old boy diagnosed with SGA, the cause of which appeared to be a burn on his hands. It is not clear why the volar surfaces usually are spared; the clinical and pathologic features of GA occurring in the palm are the same as those involving the other sites.

Figure 3. Electron micrograph shows histiocyte phagocytosing lipid droplets (arrows) and fibrinoid material (asterisk) (magnification 10,000).

The diagnosis of SGA occasionally is difficult. The history of rapid growth and multiple recurrences can mimic a malignant lesion.4,5 Subcutaneous GA typically resolves spontaneously although most lesions persist for months to years.2-8 Treatment usually is not indicated even for recurrent lesions.2-8 Nonsteroidal antirheumatics,7 dapsone,11 and intralesional injections of triamcinolone12 have been proposed for those cases resistant to spontaneous healing. An incisional or excisional biopsy examination is diagnostic but neither is curative because a recurrence and/or development of subsequent lesions may occur in a high proportion of patients.2-7 In our case we do not plan to add further therapies for the new lesion because spontaneous regression is anticipated.

Table 1. Summary of Case Reviews

Histologic examination of the lesion is necessary to differentiate it from other soft-tissue tumors that may occur in a child's hand: rhabdomyosarcoma, giant-cell fibroblastoma, fibromatosis, plexiform fibrohistiocytic tumor, epithelioid sarcoma, malignant fibrous histiocytoma, and juvenile xanthogranuloma.13-16 Immunohistochemical studies of the markers for histiocytes (CD68), muscle cells (desmin), myofibroblasts (α-smooth muscle actin), epithelial cells (cytokeratin), and endothelial cells (CD34) are useful in making the diagnosis. The pathognomonic histologie feature of SGA is a palisading granuloma showing a central zone of necrobiosis with a peripheral zone of inflammation in which the infiltrtes are in a palisading-like arrangement. Although a variety of cutaneous infections may show palisading granulomas12,17 we could not find a cause in this case by using tissue culture and special histopathologic stains. Histologically identical lesions are found in adults as either rheumatoid nodules or necrobiosis lipoidica diabeticorum. This patient, however, was a healthy child without rheumatoid disease or diabetes mellitus.

In this case the microscopic examination showed an excessive proliferation of histiocytes and the ultrastructural findings showed histiocytes with active phagocytosis of degenerated connective tissue components. Histiocytes in clinically typical GA often have an increased mitotic rate that can mimic a malignant lesion.18 Mullans and Helm19 hypothesized that a local immunologically distinct population of histiocytes proliferates after a variety of different insults, producing the reaction pattern of GA. Mesenchymal cells in the dermis are transformed into histiocytes with phagocytic properties that surround and invade collagen and elastic fibers.20 These phagocytic cells then become more activated and release enzymes such as matrix metalloproteinase (MMP)-2 and MMP-9, which further lyse the collagen and elastic fibers.21 Another interesting histologic finding was the fragmentation of elastic fibers. Hanna et al22 postulated that the degeneration of elastic fibers might promote the granulomatous reaction, leading to the formation of the typical GA. It has been suggested that the destructive potential of the inflammatory cells in GA is restricted by activation-induced apoptosis.21 We speculate that recurrence will occur when control of the lesion by apoptosis is insufficient.

References

1. Muhlbauer JE. Granuloma annulare. J Am Acad Dermatol 1980;3:217-230.

2. Felner EI, Steinberg JB, Weinberg AG. Subcutaneous granuloma annulare: a review of 47 cases. Pediatrics 1997;100: 965-967.

3. Grogg KL, Nascimento AG. Subcutaneous granuloma annulare in childhood: clinicopathologic features in 34 cases. Pediatrics 2001;107:E42.

4. Letts M, Carpenter B, Soucy P, Davidson D. Subcutaneous granuloma annulare of the extremities in children. Can JSurg 2000;43:425-430.

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;1:300-308.

6. Evans MJ, Blessing K, Gray ES. Pseudorheumatoid nodule (deep granuloma annulare) of childhood: clinicopathologic features of twenty patients. Pediatr Dermatol 1994;11:6-9.

7. 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;7:349-352.

8. Grant I, Mohammed P, Mahaffey PJ. Granuloma unnulare in the hand. J Hand Surg 2002;27B:556-558.

9. Hsu S, Lehner AC. Chang JR. Granuloma annulare localized to the palms. J Am Acad Dermatol 1999;41:287-288.

10. Mur EC, Fernandez CM, Hermosa JMH. Bilateral and subcutaneous palmar nodules in a 2-year-old child suggesting deep granuloma annulare. J Eur Acad Dermatol Venereol 2005;19:100-103.

11. Miljkovic J, Krajnc I. Subcutaneous granuloma annulare in an adult. Wien Klin Wochenschr 2003;115:309-311.

12. Chang SE. Bae GY. Moon KC, Do SH, Lim YJ. Subcutaneous granuloma annulare following herpes zoster. Int J Dermatol 2004;43:298-299.

13. Gross E, Rao BN, Pappo AS, Michalkiewicz E, Hudson MM, Kaste SC, et al. Soft tissue sarcoma of the hand in children: clinical outcome and management. J Pediatr Surg 1997;32:698-702.

14. Remstein ED, Arndt CA, Nascimento AG. Plexiform fibrohistiocytic tumor: clinicopathologic analysis of 22 cases. Am J Surg Pathol 1999;23:662-670.

15. Bullon A, Nistal M, Razquin S, Novo A, Fregenal J, Regadera J. Malignant fibrous histiocytoma in a child's hand. J Hand Surg 1986;14:744-748.

16. Janssen D, Harms D. Juvenile xanthogranuloma in childhood and adolescence: a clinicopathologic study of 129 patients from the Kiel pediatric tumor registry. Am J Surg Pathol 2005;29:21-28.

17. Su WP, Kuechle MK, Peters MS, Muller SA. Palisading granuloma caused by infectious diseases. Am J Dermatopathol 1992;14:211-215.

18. Trotter MJ, Crawford RI, O'Connell JX, Tron VA. Mitotic granuloma annulare: a clinicopathologic study of 20 cases. J Cutan Pathol 1996;23:537-545.

19. Mullans E, Helm KF. Granuloma annulare: an immunohistochemical study. J Cutan Pathol 1994;21:135-139.

20. Reed R. Connective-tissue activation. Am J Dermatopathol 1982;4:365-376.

21. Fayyazi A, Schweyer S, Eichmeyer B, Herms J, Hemmerlein B. Radzun HJ, Berger H. Expression of IFN γ, coexpression of TNFa and matrix metalloprotcinases and apoptosis of T lymphocytes and macrophages in granuloma annulare. Arch Dermatol Res 2000;292:384- 390.

22. Hanna WM, Moreno-Merlo F, Andrighetti L. Granuloma annulare: an elastic tissue disease? Case report and literature review. Ultrastruct Pathol 1999;23:33-38.

Junji Takeyama, MD, Takehiko Sanada, MD, Mika Watanabe, MD, Masahito Hatori, MD, Nagisa Kunikata, MD, Setsuya Aiba, MD

From the Departments of Pathology and Plastic Surgery, Miyagi Children's Hospital; the Department of Pathology, Tohoku University Hospital; and the Departments of Orthopaedic Surgery and Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.

The authors would like to express their thanks to Ms. Shizue Mochizuki, Department of Pathology, Tohoku University Hospital. Sendai. Japan, for her help in the ultrastructural study.

Received for publication May 24. 2005: accepted in revised form October 6. 2005.

No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

Corresponding author: Junji Takeyama, MD, Department of Pathology. Miyagi Children's Hospital 4-3-17 Ochiai, Aoba-ku, Sendai, 989-3126 Japan; e-mail: jtakeyama@miyagi-children.or.jp.

Copyright 2006 by the American Society for Surgery of the Hand

0363-5023/06/31A01-0019$32.00/0

doi: 10.1016/j.jhsa.2005.10.003

Copyright Churchill Livingstone Inc., Medical Publishers Jan 2006

Source: Journal of Hand Surgery, The

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