Samir K. El-MoJty, DMD, .F’I?D,~ and Daniel Santa Cruz, MD,b St. Louis, MO.

WASHINGTON UNIVERSITY- SCHOOL OF MEDICINE

The subepidermal calcified nodule, also known as cutaneous calculi, is a form of idiopathic calcinosis that affects children and is occasionally present at birth. It occurs usually in the faciai skin and has no relationship to connective tissue disease or to any abnormality in calcium or phosphorus metabolism. The oral cavity is very rarely affected by calcinosis cutis of any type, and idiopathic calcinosis has not been previously reported in the oral mucosa. This is a report of two cases of calcified nodules that occurred in the gingiva of a l-year-old girl and the tongue of a 5-year-old boy. The lesions showed clinical, histologic, and histochemical similarities to the subepidermal calcified nodule. The name orai mucosal calcified nodule is proposed for this form of calcinosis. (ORAL SURG ORAL MED ORAL PATWOL 1992;73:472-5)

aicinosis cutis, or pathologic calcification of the skin, is manifested histologically as small or large calcium deposits in the dermis or subcutis surrounded by a foreign body reaction. Calcinosis cutis is classi- fied into three main types’: metastatic, dystrophic, and idiopathic calcinosis. Metastatic calcinosis cutis is caused by hypercalcemia and hyperphosphatemia. In dystrophic calcinosis the calcium is deposited in previously damaged tissue in normocalcemic and normophosphatemic patients. Two main types are known: calcinosis universalis with numerous large deposits and calcinosis circumscripta with few depos- its. As in metastatic calcinosis, the calcified material is found as granules or small deposits in the dermis and as massive deposits in the subcutis.

The third type of calcinosis cutis is less well defined and has no known pathogenetic mechanism.‘, 2 It is commonly referred to as idiopathic calcinosis. The three known main types of idiopathic calcinosis cutis are tumoral calcinosis, calcinosis of the scrotum, and subepidermal calcified nodule. Tumoral calcinosis3* 4 is manifested as subcutaneous deposits of calcium that occur in periarticular locations and resemble tu- mors. It is known to affect more than one sibling in the

Presented at the annual meeting of the Academy of Oral Pathol- ogy in San Diego, Calif., in April 1990. “Professor of Oral Pathology, Division of Surgical Pathology. bDirector of Cutaneous Pathology, St. John’s Mercy Medical Cen- ter, and Visiting Associate Professor of Pathology. 7/14/30988

same family, and hyperphosphatemia has been ob- served in some instances.4, 5

Idiopathic calcinosis of the scrotum occurs as mul- tiple nodules of the scrotal skin that appear in child- hood and early adult life and subsequently increase in size and number.6 Some authors believe the patho- genesis of these nodules is the result of calcification in various preexisting cysts including epidermal, ec- crine, and pilar.” 7: *

The subepidermal calcified nodule, also known as cutaneous calculi, usually occurs as a single small, raised, hard nodule in the facial skin.‘, 9-*1 It affects Tredominantly children and is occasionally present at birth.9 There is no relationship to connective tissue disease, and the blood chemistry is normal.

Involvement of the oral mucosa in calcinosis cutis Ls extremely rare. Only two such cases have been re- ported in the English-language literature. One patient was a 3-year-old Indian boy w-ho had dermatomyosi- 5s with widespread calcified deposits.12 The oral lesions included calcified masses in the floor of the .mouth and cheek. The other was a case of the milk- alkali syndrome in a 68-year-old man with a sublin- gual-submandibular calcific mass associated with several periarticular calcified lesions of the extremi- t.ies.13 Idiopathic calcinosis has not, to the best of our knowledge, been previously reported in the oral cav- ity or in any other mucosal surface. This is a report of two cases of idiopathic calcification of the oral mu- cosa that are histologically and histochemically sim- ilar to the subepidermal calcified nodule of the skin.

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Fig. 1. Case 1. Histologic section of mucosal lesion shows areas of pooled matrix containing calcified deposits. Mild foreign body reaction is present in connective tissue septae. (Hematoxylin-eosin smin; original magnification, X90.)

Fig. 2. Case 2. Mucosal lesion shows advanced foreign body reaction. Areas of calcifying matrix are reduced. (Hematoxylin-eosin stain; original magnification, x90.)

CASE REPORTS Case 1

A l-year-old white girl had a soft nodule in the gingiva, palatal to the right maxillary central deciduous incisor. The lesion grew slowly within a period of 3 months and caused labial displacement of the incisor. The covering mucosa was intact and of normal clolor, and the patient was well devel- oped and had no history of connective tissue disease or cal- cium or phosphorus abnormality. The lesion was excised.

Case 2

A 5-year-old white boy had a hard nodular lesion about 1 cm in diameter on the anterior dorsal surface of the tongue. Extrusion of calcified material from the site of the lesion occurred frequently during a prolonged period. At the time of examination the covering mucosa appeared normal. The patient was ,well developed and had no history of con- nective tissue disease or any abnormality in calcium or phosphorus metabolism. The lesion was excised.

HISTOLOGIC TECHINIQUES AND FINDINGS

The formalin-fixed specimens were processed for routine light microscopic examination, and the sec-

tions were stained with hematoxylin and eosin. Addi- tional sections were cut from both specimens and stained with the following histochemical stainst4: von Kossa; alcian blue at pH 3.0 and pH 0.5; and tolui- dine blue at pH 3.0 and pH 1.5, with and without hy- aluronidase digestion.

The histologic findings in both cases were generally similar. Pools of calcifying homogeneous basophilic matrix were present subepithelially in the connective tissue of the mucosa and were surrounded by a foreign body reaction. These areas extended deep in the mu- cosa (Figs. 1 and 2) and into the muscle layer of the tongue in the second case (Fig. 3). The two lesions differed mainly in their stage of maturation. In case 2, the process was more advanced with regard to cal- cification and extent of the foreign body reaction (Figs. 2 and 3). The calcified deposits formed aggre- gated globules or larger structures and psammoma- like bodies (Figs. 1 to 3). These structures showed positive reactivity with von Kossa stain whereas the matrix was negative. Macrophages and multinucle- ated cells constitu.ted the foreign body reaction in the connective tissue. The cytoplasm of many giant cells

‘DR.&L SURG URAL ?Vi\/iEJ %A; PATHOL April 1992

ig. 3. Case 2. Extension of pathologic calcification into muscle layer of the tongue. Both calcification and foreign body reaction are prominent. (Hematoxylin-eosin stain; original magnification, X90.)

and some macrophages contained pha.gocytosed cal- cified particles (Fig. 4).

The calcifying homogenous matrix stained posi- tively with alcian blue at pH 3.0 and less intensely at pH 0.5. It also stained metachromatically with tolu- idine blue. The metachromasia was more marked at pH 3.0 than at pH 1.5. The material also showed some positivity with alcian blue staining after hyaluroni- dase digestion.

hn both reported cases a nodular oral lesion was detected in young children, neither of whom had a history of connective tissue disease or calcium or phosphorus abnormality. In the first case the patient was 1 year old, and her gingival lesion was of 3 months’ duration. In case 2 the patient was a Syear- old boy. His tongue lesion was of longer duration with recurrent extrusion of calcified masses. Histologi- cally, the lesion in the latter case was more mature with regard to the extent of the calcification and the foreign body reaction. In both cases calcification took

ig. 4. Case 2. Higher magnification view of foreign body reaction. Cytoplasm of several giant cells show phagocy- tosed calcified particles. (Hematoxylin-eosin study; original magnification, X90.)

place in a homogeneous basophilic matrix. His- tochemical stains showed positive staining of the cal- cifying matrix with alcian blue and metachromasia with toluidine blue at pH 3.0. In both cases staining was positive albeit less intense at more acidic pH val- ues of 1.5 and 0.5. Prior hyaluronidase digestion did not totally eliminate the alcian blue positivity. These findings suggest that the amorphous basophilic mate- rial is composed of sulfated and nonsulfated acid mu- copolysaccharides, most likely hyaluronic acid and chondroitin sulfate. Similar findings have been re- ported in the subepidermal calcified nodule.r, l1

The pathogenetic mechanism leading to accumu- lation of this material in the dermis or mucosa is not known. It has been postulated that calcification in the subepidermal calcified nodule occurs within a homo- geneous matrix originating from specific preexisting structures such as sweat glands’ or nevus cells.1° It has also been suggested that the matrix might be pro- duced by degranulation of mast cells.” In mucosal calcified nodules we found no evidence to support ei- ther of these two hypotheses. There were no mast cells or any specific structures in the connective tissue in the vicinity of the lesions. An exogenous origin of the calcified material is unlikely because there was no history of trauma and calcification occurred in a gly- cosaminoglycan matrix.

The two oral lesions were similar to the subepider- ma1 calcified nodule in several respects: they occurred as solitary calcified nodules in children with no known connective tissue disease,. or calcium or phosphorus abnormality. The calcified deposits were present in the connective tissue immediately under the epithe- lium, within a matrix of sulfated and nonsulfated acid proteogiycans. The exact mechanism that leads to

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excessive production and pooling of this ground sub- stance and its subsequent calcification is not clear. It seems likely that this substance is produced by fibro- blastic cells in the area. The history of extrusion of calcified particles and of the progressive foreign body reaction suggests that these lesions might resolve spontaneously with time. This might explain their absence in adults. We propose the term mucosal cal- cified nodule of the oral cavity for this lesion.

REFERENCES 1, Lever WF, Lever GS. Histopathology of the skin. Philadelphia:

JB Lippincott, 1990:466-9. 2. Haim S, Friedman-Elirnbaum R. Two cases of circumscribed

calcinosis. Dermatologica 1971;143:111-4. 3. Whiting DA, Simson IW, Kallmeyer JC. Unusual cutaneous

lesions in tumoral calscinosis. Arch Dermatol 1970;102:465-73. 4. Pursley TV, Prince MJ, Chausmer AB. Cutaneous manifesta-

tions of tumoral calcinosis. Arch Dermatol 1979;115:1100-2. 5. Mozaffarian G, Lalferty FW, Pearson OH. Treatment of tu-

moral calcinosis with phosphorus deprivation. Ann Intern Med 1972;77:741-5.

6. Shapiro L, Platt N, Torres-Rodriguez VM. Idiopathic calci- nosis of the scrotum. Arch Dermatol 1970;102:199-204.

7. Swinehart JM, Gelitz LE. Scrotal calcinosis, dystrophic calci- fication of epidermal cysts. Arch Dermatol 1982;118:985-8.

8. Song DH, Lee KH, Kang WH. Idiopathic calcification of the scrotum. J Am Acad Dermatol 1988;19:1095-101.

9. Winer LH. Solitary congenital nodular calcification of the skin. Arch Dermatol Syph 1952;66:204-11.

10. Woods B, Kellaway TD. Cutaneous calculi. Br J Dermatol 1963;75:1-11.

11. Tezuka T. Cutaneous calculus: its pathogenesis. Dermatolog- ica 1980;161:191-9.

12. Sanger RG, Kirby JW. The oral and facial manifestations of dermatomyositis with calcinosis. ORAL SURG ORAL MED ORAL PATHOL 1973;35:476-88.

13. Wiggins HE, Karian BK, Smith BM. Sublingual-submandible calcific mass associated with tumoral calcinosis in a patient with suspected milk-alkali syndrome. ORAL SURG ORAL MED ORAL PATHOL 1975;40:8-18.

14. Luna LG. Manual of histologic staining methods of the Armed Forces Institute of Pathology. New York: McGraw-Hill, 1968:163-9.

Reprint requests: Samir K. El-Mofty, DMD, PhD Professor of Oral Pathology Division of Surgical Pathology Oral Pathology Section Washington University School of Medicine One Barnes Hospital Plaza St. Louis, MO 63110