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Turkish Neurosurgery 2007, Vol: 17, No: 1, 19-22

Hakan SABUNCUO⁄LU1

Kamil ÖGE2

Figen SÖYLEMEZO⁄LU3

Arzu SA⁄LAM4

1 Neurosurgery Department, Ufuk University School of Medicine, Ankara-Turkey

2 Neurosurgery Department, Ankara Güven Hospital, Ankara-Turkey

3,4 Pathology Department, Hacettepe University,School of Medicine, Ankara-Turkey

Received : 18.01.2007Accepted : 21.02.2007

* This case report was presented at the 17th Scientific Congress of TNS, 20-24 May 2003, Antalya, Turkey

Correspondence address:Hakan SABUNCUO⁄LUKoza Sokak No:72/3606700 Gaziosmanpafla-Ankara, TurkeyPhone : +90 312 44744 83E-mail : hsabuncuoglu@hotmail.com

Subcutaneous GranulomaAnnulare of the Scalp inChildhood: A Case Reportand Review of the Literature

ABSTRACTGranuloma annulare is a benign inflammatory skin lesion of unknown etiologythat is usually seen in adults and children and subtypes of it includes localizedgranuloma annulare, generalized granuloma annulare, subcutaneousgranuloma annulare and arcuate dermal erythema. Etiology and pathogenesisof granuloma annulare are obscure, although there is much evidence for animmunologic mechanism. Precipitating factors are insect bites, sunburn,photochemotherapy, drugs, physical trauma, acute phlebitis and sepsis afters u rg e r y. Some investigators were suggested a relationship of granulomaannulare to a latent or clinically manifest diabetes or rheumatoid arthritis. Incontrast, an association of subcutaneous granuloma annulare with thesediseases in childhood has not been reported in the literature. Subcutaneousgranuloma annulare of the scalp is rare lesion in childhood and nodules on thescalp are usually non-, or slightly mobile, whereas lesions on the extremities arefreely mobile. For definitive diagnosis, a biopsy should be performed but wides u rgical intervention or medical treatment is not indicated. In case ofrecurrence, no additional diagnostic studies are necessary.KEY WORDS: Childhood, Scalp, Subcutaneous granuloma.

INTRODUCTIONGranuloma annulare (GA) is a common, self-limited, benign

inflammatory skin lesion of unknown etiology that is usually seen inboth adults and children. Subtypes with distinct clinical feature sinclude localized granuloma annulare (LGA), generalized granulomaannulare (GGA), subcutaneous granuloma annulare (SGA) and arcuatedermal erythema (3,4). Different authors have referred to the samecondition as benign rheumatoid nodule, pseudorheumatoid nodule,isolated subcutaneous nodule, subcutaneous palisading granuloma andpalisading granuloma nodosum (2). Although SGA is seen exclusivelyin children, most cases are reported in surgical, pathology ordermatologic journals with little information in the general pediatricliterature (3).

CASE REPORTA 2 - y e a r-old girl was admitted to our hospital with thre e

subcutaneous scalp masses. Two of these were in the rightoccipitoparietal area and 6 and 5 mm in diameter respectively and onewas in the occipital area and 4 mm in diameter. In history, we learnedthat these masses were appeared 15 days before without any traumaand grew up in days. The lesions were immobile, nontender and no

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Turkish Neurosurgery 2007, Vol: 17, No: 1, 19-22 Sabuncuoğlu: Subcutaneous Granuloma Annulare of the Scalp in Chilhood

the areas of altered collagen. Occasional foreignbody giant cells are present. Immunohistochemicallythese histiocytes were characterized by Mac 387 andCD68 expression. A diagnosis of palisadinggranuloma was confirmed. No recurrences or newmasses were determined in the scalp subcutaneoustissue of this patient during two-year follow up.

other dermatologic lesion was observed over theskin. No abnormality was determined during theneurological examination and the remainder of thephysical examination. Laboratory tests revealed anormal complete blood count, antistreptolysin O,erythrocyte sedimentation rate, rheumatoid factor,blood glucose level and anti-nuclear antibody level.Cranial computed tomography with intravenousadministration of contrast substance showed 2 rightoccipitoparietal and one occipital subcutaneousmasses without any bone destruction orhyperosteosis (Figure 1). The masses were totallyexcised to prevent an increase in size. They werehard, involved the galea, tight on the periosteumand immobile. Histologically, the lesion wascomposed of palisading granulomas in thesubcutaneous tissue. The granulomas werecharacterized by a well-demarcated zone ofdisintegrating extracellular material mixed with celldebris surrounded by a cuff of radially orientedf i b roblasts varying with lymphocytes andhistiocytes (Figure 2). The centrally located materialhad the appearance of collagen and elastic fibers intrichrome staining (Figures 3). Mucin was present in

Figure 1: On cranial computed tomography withintravenous 1 administraton of cnotrast substance, rightoccipitoparietal and one occipital subcutaneous massesw e re seen without any bone destruction andhyperosteosis.

Figure 2: Typical granuloma with palisading histiocytesaround necrobiotic collagen center (HE, x 20).

Figure 3: Typical granuloma with palisading histiocytesaround necrobiotic collagen center (Trichrome staining, x20).

DISCUSSIONGA was first described by Fox in 1895. Ziegler, in

1941, was the first to note the histological similarityof the isolated nodule seen in GA to the nodules seenin rheumatoid arthritis (3). The etiology andpathogenesis of GA are obscure, although there ismuch evidence that an immunologic mechanism,p robably a delayed-type hypersensitivity, isinvolved (10). Immunologic studies of lymphocytessubsets and serum monocyte-modulating factorssupport the hypothesis that GA is the result of anaberrant cell-mediated immune response (2). Morerecently, vasculitis and cellular immunity have beenhypothesized to play a role in GA.

Regarding the etiology, there is no good evidencefor putative causes of SGA including tuberculosis,trauma, streptococcal infection, thyroid disease,Epstein-Barr virus, herpes zoster/varicella orcollagen disord e r. The majority of cases werereported in the first three decades of life (89% inMuhlemann and Williams' study, 79% in Andersenand Verdich's study, 62% in Studer's study) (10) .Reported precipitating factors of GA are insect bites,sunburn, Psoralen UV-A (PUVA), drugs, physicaltrauma, acute phlebitis and sepsis after surg e r y(1,10). Although there is no relationship betweenemotional stress and SGA, Studer mentioned that15% of their patients reported stress situations as atrigger of recurrences.

The study and treatment of patients with SGA ofall types generates controversy and confusionbecause widely variant clinical syndromes can beseen, the histology mimics other disorders andeffective therapy remains to be undetermined (3).Adults presenting with rheumatoid nodules,histologically identical to SGA, are at significant riskfor the development of rheumatoid arthritis or otherconnective tissue disease (2). Because of thisassociation, efforts have been made to determinewhether children with these lesions are at similarrisk. Draheim et al (4) collected 54 cases at theArmed Forces Institute of Pathology in 1959; in nocase did connective tissue disease develop after 1 to14 years follow-up. Subsequent reports with smallernumbers of cases have also concluded that there isno increased risk for systemic rheumatologic diseasein the children (3).

Although the association of SGA with diabetesmellitus is not yet established (4), severalinvestigators have attempted to demonstrate a

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Turkish Neurosurgery 2007, Vol: 17, No: 1, 19-22 Sabuncuoğlu: Subcutaneous Granuloma Annulare of the Scalp in Chilhood

relationship of SGA with other systemic diseases,most notably with diabetes mellitus (4,7,9,10). Thereason for searching for a relationship betweendiabetes mellitus and SGA is similarhistopathological features with necrobiosis lipoidicad i a b e t i c o rum, a well-recognized dermatologiccomplication of diabetes mellitus. In contrast, anassociation of SGA with diabetes mellitus inchildhood has not been published in the medicalliterature (5).

Various diseases have been reported to involvethe subcutaneous portion of the scalp in childhood.These include osteoma, eosinophilic granuloma,cranial fasciitis, palisading granuloma, sarcoidosis,f i b rous dysplasia, dermoid tumor, traumaticgranuloma, abscess, hemangioma, sinus pericraniiand primary sarcoma (5). The differential diagnosisof subcutaneous nodules of the scalp and/ore x t remities is extensive and includes trauma,infection, tumor, metabolic bone or skin disease andinflammatory/autoimmune disease. All of the abovecan be ruled out with a proper history, focusing onissues regarding diet, weight loss and/or fever (3).

S G A most often manifests as a larg e ,asymptomatic soft tissue mass. Although nodulesare usually stable for months, they may rapidlyenlarge over the course of weeks. The typical lesionsof SGA a re single or multiple, small, pinkish,nonulcerated nodules in the deep subcutaneoustissue. As shown in current studies, the mostcommon lesion location is lower extre m i t y,especially the pretibial area, followed by the hands(4). The buttocks, forehead and scalp are lesscommonly affected. Deep dermal or subcutaneousnodules on the extremities are attached to fascia andare often therefore mobile, whereas lesions on thescalp are attached to underlying periosteum and aretherefore fixed or only slightly mobile. SGA of thescalp is a rare lesion in childhood and presents withimmobile, nontender masses that are multiple andtend to vary in size over time (5). On histologicalevaluation, these nodules are similar to the nodulesseen in adults with rheumatoid arthritis and to thelesion recognized in adult diabetic patients asnecrobiosis lipoidica diabeticorum (4). The typicalhistology shows that the focus of the lesion has acentral core of incomplete and mostly reversiblechange (necrobiosis) of connective tissue,surrounded by a wall of palisaded histiocytes. Then e c robiotic centers are usually oval in outline,

slightly basophilic, devoid of nuclei and marked bya loss of outline of collagenous and elastic tissuefibers. Characteristically, the necrobiotic focus is notso large or deeply situated as those of rheumatoidnodules or as broad and diffuse as those ofnecrobiosis lipoidica (diabeticorum). If an accuratehistory is not available, simple laboratory testsincluding a complete blood count (CBC), plainradiograph and erythrocyte sedimentation rate(ESR) may be obtained for laboratory investigation.Further serologic studies such as antinuclearantibody, rheumatoid factor, complement and C-reactive protein are uniformly negative andprobably not warranted (2). In case of benign historyand normal examination except the nodules, noadditional work-up is necessary (3). The presence orabsence of calvarial invasion is an importantconsideration in the diagnosis: Plain radiographsshow a soft tissue mass without bony involvement,calcification, or ossification. Cranial computerizedtomography is useful for this assessment and helpsrule out calvarial invasion. The possible value ofmagnetic resonance imaging findings ind i ff e rentiating between types of subcutaneousmasses has not been sufficiently clarified.

Although the clinical profile is characteristic, thedefinite diagnosis is based upon biopsy study andexcisional biopsy should provide an adequatespecimen in all cases. Therapy for these lesions hasalso varied. Most have been treated by excisionalb i o p s y. Unfortunately, some patients haveunnecessarily been treated with wide local excisionthat has required subsequent skin grafting (7). Sincemultiple lesions develop in many of these children,there has been a tendency to surgically excise themas they re c u r. However, the knowledge in theliterature supports the fact that these lesions willregress over time if left alone. Medical therapy in theform of steroid injections, antibiotics, potassiumiodine, dapsone, niacinamide, chlorambucil,isoretionin, retinoids (vitamin A derivates), PUVAand aspirin has also been attempted and found to beof no value (3,8).

The prognosis for children with these lesions isexcellent. Although subsequent additional lesionswill develop in some, they are self-limiting. A fineneedle aspiration of a new lesion may serve to

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Turkish Neurosurgery 2007, Vol: 17, No: 1, 19-22 Sabuncuoğlu: Subcutaneous Granuloma Annulare of the Scalp in Chilhood

re a s s u re the physician that the lesion is indeedbenign. In a child with a negative history, otherwisenormal physical examination and normal ESR, theseappears to be no increased risk for the developmentof any systemic collagen vascular disease over that ofthe general population (8). Spontaneous resolutionof SGA has occurred within 2 years in 50% of cases,although lesions may last weeks to decades.Recurrence, often at the same site, is noted 40% ofcases.

In summary, no additional studies are necessaryif the history and physical examination correlatewith SGA. A biopsy should be performed for adefinite diagnosis but wide surgical excision ormedical treatment is not indicated. Recurre n c e slocally or at other sites are common but usually donot need additional biopsy procedures (11).

REFERENCES1. Dabski K, Winkelmann RK. Generalized granuloma annulare:

clinical and laboratory findings in 100 patients. J Am AcadDermatol: 20(1):39-47, 1989

2. Davids JR, Kolman BH, Billman GF, Krous HF. Subcutaneousgranuloma annulare: recognition and treatment. J PediatrOrthop:13(5): 582-586, 1993

3. Felner EI, Steinberg JB, We i n b e rg AG. Subcutaneousgranuloma annulare: a review of 47 cases. Pediatrics:100(6):965-967, 1997

4. G rogg KL, Nascimento AG. Subcutaneous granulomaannulare in childhood: clinicopathologic features in 34 cases.Pediatrics: 107(3):42, 2001

5. Hata N, Inamura T, Imayama S et.al. Multiple palisadinggranulomas in the scalp of an infant: a case report. SurgNeurol: 56(6):396-399, 2001

6. Hutcheson AC, Hurray DH, Smith MT, Shannon A B .Subcutaneous granuloma annulare of the scalp: a case reportand case review. Cutis: 76(6):377-82, 2005

7. Kossard S, Goellner JR, Su WP. Subcutaneous necrobioticgranulomas of the scalp. J Am Acad Dermatol: 3(2):180-185,1980

8. Minifee PK, Buchino JJ. Subcutaneous palisading granulomas(benign rheumatoid nodules) in children. J Pediatr Surg:21(12):1078-1080, 1986

9. Muhlemann MF, Williams DR. Localized granuloma annulareis associated with insulin-dependent diabetes mellitus.Muhlemann MF, Williams DR. Br J Dermatol: 111(3):325-329,1984

10. Studer EM, Calza AM, Saurat JH. Precipitating factors andassociated diseases in 84 patients with granuloma annulare: aretrospective study. Dermatology: 193(4):364-368, 1996

11. Takeyama J, Sanada T, Watanabe M, Hatori M, Kunikata N,Aiba S. Subcutaneous granuloma annulare in a child's palm: acase report. J Hand Surg: 31(1):103-6, 2006