Inflammatory pseudotumors in the buccal tissues of children

Inflammatory pseudotumors in the buccal tissues of children S. L. Liston, F. R.A.C.S., F.R.C.S., L. P. Dehner, M.D., C. W. Jarvis, M.D., C. Pitzele, M.D., and T. L. Huseby, M.D., Minneapolis, Minn. DEPARTMENTS SURGICAL

OF OTOLARYNGOLOGY, PATHOLOGY

DEPARTMENT

AND

OF PATHOLOGY,

PEDIATRICS, ST. PAUL

LABORATORY

MEDICINE

UNIVERSITY CHILDREN’S

AND

OF MINNESOTA

PATHOLOGY, MEDICAL

DIVISION SCHOOL,

OF AND

HOSPITAL

Inflammatory pseudotumor is a nonneoplastic lesion of unknown origin. Most cases occur in the respiratory tract or orbit. This study reports three cases, all involving children, of rapidly enlarging masses in the soft tissues of the oral cavity. They were initially suspected to be malignant but proved to be inflammatory pseudotumors. The histologic appearance was that of a fibroproliferative process containing chronic inflammatory cells. The pleomorphism and mitotic activity of the fibroblasts were worrisome features. Regression without sequelae occurred in all three patients.

A

rapidly enlarging mass in the oral cavity of a child who is otherwise asymptomatic presents a disturbing problem. The head and neck region and particularly the oral cavity may be the site of such neoplasms as embryonal rhabdomyosarcoma, vascular tumor, metastatic neuroblastoma, fibromastosis with aggressive local growth, non-Hodgkin’s malignant lymphoma, and acute leukemia.’ Within a brief period of time, we had the opportunity to study three children who presented in virtually identical fashions and had very similar cellular lesions designated as “inflammatory pseudotumor.” The nosology and possible pathogenesis are reviewed. CASE REPORTS Case 1

A 4-year-old girl had a mass in the right cheek which had been present for less than 1 week when she was seen by a family practitioner. The mass measured approximately 1 by 1 cm. when initially examined. There was no history of preceding injury or infection in the area of the cheek. The child was afebrile. The white cell count was 8,800 per cubic millimeter. Oral peniciliin therapy was started. In 1 week there had been marked enlargement to 4 by 5 cm. (Fig. 1). Tenderness was not elicited, but the masswas quite hard and adherent to the mandible. There were no mucosal lesions in the nose, nasopharynx, oropharynx, or hypopharynx. Cutaneous erythema and other evidence of infection on the face or scalp were not evident. There was no regional lymphadenopathy. The 0030.4220/81/030287

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1981

The C. V. Mosby Co.

Fig. 1. Case 1. Clinical photograph of mass in cheek without evidence of overt inflammatory changes.

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Fig. 2. Case 2. Stellate appearance of inflammatory pseudotumor with misture of tibroblasts and chronic inflammatory cells. Despite brevity of clinical history, very few neutrophils were apparent. (Hematoxylin and eosin stain. Magnification X50).

child was alert and active, without any apparent malaise. A roentgenograph of the mandible failed to show bone erosion, and there was no sign of a dental infection. Eight days after the initial presentation the child was taken to the operating room. The clinical impression at that time was that of a soft-tissue sarcoma, probably a rhabdomyosarcoma. Neither fluid nor pus could be aspirated from the mass, but the blood and tissue were sent for microbiologic cultures. An incisional biopsy was performed through the buccal mucosa. The mass appeared encapsulated, with a line of demarcation between it and the surrounding tissues. The surface of the mass was uniformly pink. Cystic and hemorrhagic areas were not apparent, and the cut surface did not bleed. During the next 2 days the mass continued to enlarge, but by the fourth day after surgery the mass had ceased its apparent growth. The incision healed satisfactorily. The cultures were negative for bacteria and fungi. A pathologic diagnosis of inflammatory pseudotumor was made. Over the next 3 weeks, the mass decreased in size to the point that a remnant was barely palpable. Four months later, the patient was readmitted with a swelling in the same area. This swelling differed from the

original mass in that it was more obviously inflammatory, with erythema, tenderness, and warmth. Her temperature was 37.6 “C. Four days later aspiration in the operating room yielded approximately 1 C.C. of purulent material which, on Gram staining, was positive, for cocci and neutrophils. The area of the abscess was opened through the previous incision. An encapsulated abscess cavity was not identified, and no foreign bodies were found. Tissue similar to the inflammatory pseudotumor was not found. The wound was left open to granulate, and it healed without further problems. The patient has been well for the past 6 months. Case 2

A 19-month-old Korean child was admitted to St. Paul Children’s Hospital with 4-day history of swelling of the left cheek and associated induration. There was no history of trauma, and the parents originally thought that the swelling may have been due to an insect bite. At the time of admission her temperature was 38’ C. The hemoglobin was 13.2 gram/d1 and the white cell count was 12,000/ mm n with 50 percent neutrophils and 23 percent lymphocytes. The purified protein derivative was negative. Man-

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Fig. 3. Case 1. Loose myxoid stroma containing plump fibroblasts and occasional dense eosinophilic bands of collagen was noted centrally in the lesion (Hematoxylin and eosin stain. Magnification x 300.)

dibular radiographs showed only soft-tissue swelling. Two blood cultures were obtained, and there was no growth. The mass continued to enlarge to 5 by 3 cm. Two weeks after admission the patient was taken to the operating room, and a biopsy specimen was obtained through a skin incision 1.5 cm below the mandible. The area was inflamed, but no pus was found. It appeared as though the area of swelling was circumscribed by a pseudocapsule. There was no obvious cystic formation or suppuration. The pathologic diagnosis was inflammatory pseudotumor. The wound healed well, and over the next month the induration resolved spontaneously. Since then the child has remained well for 10 months. Case 3

A 6-year-old boy presented to his family practitioner with a l-day history of right-sided facial swelling. This swelling was thought to be either a lymph node or the submandibular gland. There was no sore throat or other symptom of an infection which might have produced lymphadenitis. The patient’s temperature was 37.8” C. The hemoglobulin level was 11.7 gm/dl, and the white cell count was 11,000/mm3 with 72 percent segmented

cells, 2 percent bands, and 25 percent lymphocytes. The patient was started on erythromycin. Two days later he was admitted to the hospital, as the swelling had increased considerably. He remained afebrile, and the white cell count had fallen to 9,500/mm3. It was thought that the swelling might have been due to a dental infection, but dental roentgenograms were normal and mandibular roentgenograms showed only soft-tissue swelling. Treatment with penicillin and Keflin in combination was then started. Throat cultures and nasal cultures grew only normal flora, and blood cultures revealed no growth. The mass,which had increased to 4 by 5 cm., was fixed to the mandible and the overlying skin was reddened. The mass was not particularly tender. Because of our experience with the first two cases,we were suspicious of an inflammatory pseudotumor. An intraoral biopsy specimen was obtained, and a frozen section revealed an inflammatory process.The permanent sections confirmed the diagnosis of inflammatory pseudotumor. At the time of the biopsy the masswas described as fibrotic, inflamed tissue, and no capsule was noted. Although the biopsy was performed intraorally, a small area of skin broke down and drained for a week. The incision was left to granulate, and it

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healed well. Over the next month the mass resolved spontaneously and the child has remained well ever since. PATHOLOGIC

FINDINGS

The histologic findings were virtually identical in all cases. Microscopically, the lesions as biopsied were not encapsulated but circumscribed, with involvement of the subcutaneous fat (Fig. 2). Salivary gland tissue was not identified. There were delicate bands of connective tissue which radiated into the adjacent fat. Centrally, a mixture of, cell types was evident, including plump and spindleshaped fibroblasts in a myxoid to collagenous stroma (Fig. 3). Mitoses were relatively abundant, but none were bizarre or atypical. Small lymphocytes, plasma cells, histiocytes, and occasional eosinophils were the principal inflammatory elements (Fig. 3). Collections of neutrophils in the form of microabscesses were not found. Histologic stains for microorganisms yielded negative results. The interpretation in each case was that of an “inflammatory pseudotumor” of unknown origin. DISCUSSION

All three children described in this report presented in very similar fashions, each with a rapidly enlarging mass in the soft tissues of the cheek. The children’s temperatures and white cell counts were either normal or only slightly elevated. None of the children had an obvious source of infection. In each case the physical examination and roentgenographic studies indicated the presence of an exclusive soft-tissue process. Preoperatively, we strongly suspected that this might be a malignant soft-tissue neoplasm. Surgical exploration revealed a circumscribed, solid, mass in the soft tissues. Suppuration was apparent only in the first patient (Case 1) when the mass recurred 4 months after the initial presentation. Histopathologically, the biopsy findings were essentially identical in these children; all showed a predominantly fibroproliferative process with a prominent mixed inflammatory infiltrate, most notable in the center of the lesion. There was not a striking vascular component, and thus the reaction did not qualify as a granulation tissue response. It was clearly inflammatory, yet the pleomorphism of the fibroblasts, brisk mitotic activity, and the grossly tumefactive nature were synthesized into the term injlammatory pseudotumor. The term injlammatory pseudotumor is a somewhat confusing and possibly ambiguous designation for a recognized entity of unknown etiology. The interrelationship between these entities in various

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parts of the body is confusing, and no wellrecognized classification has yet been devised. There are many unresolved points concerning the pathogenesis and even the histogenesis when one considers the elastofibroma and fibrohistiocytic group of neoplasms in children such as the fibrous histiocytoma, the histiocytoma, and the juvenile xanthogranuloma. Cozzutto and associates’ have described five fibrohistiocytic retroperitoneal tumors in children, each with a striking chronic inflammatory infiltrate. Thus, the presence of the inflammatory cells in our cases was not immediately interpreted as indicative of absolute benignancy. The fibrohistiocytic tumors are well known for their potentially lethal behavior, even in children.,’ Yet another histogenetic and differential diagnostic consideration was the pseudosarcomatous proliferation known as “nodular fasciitis.“‘. 3 The cellular common denominator to the fibrohistiocytic lesions and nodular fasciitis is the seemingly ubiquitous myofibroblast.“. 7 Since electron microscopy was not performed in either of our cases, these various points must remain speculative. The respiratory tract and orbit are the most familiar sites of the inflammatory pseudotumor, but Pisciotto and co-authors8 reported an abdominal plasma cell pseudotumor in a 2-year-old girl. In the respiratory tract, the trachea, mainstem bronchi, and pulmonary parenchyma are the most frequently affected locations.!’ As noted previously in the description of the “plasma cell pseudotumor” of the abdomen, Bahadori and Liebow’” mentioned the prominence of plasma cells in the respiratory tract lesions and suggested the designation of plasma cell granuloma. Other authors have been equally impressed with the histiocytic or macrophagic component and thus used the appelation of xanthomatous pseudotumor.” In the orbit, the inflammatory pseudotumor has been reported in association with Wegener’s granulomatosis, but most cases in this site have an unknown etiology.” Gonzalez-Crussi and colleagues’” described a very unusual tumor in the right atrium of the heart in a 5-year-old child. It was composed histologically of variably cellular connective tissue, small lymphocytes, and plasma cells, not unlike the appearance of the tumors in our cases. They likewise considered their case a probable example of an inflammatory pseudotumor. Oral pathologists have recognized for some time that the connective tissues and epithelium of the oral cavity may respond to defined or poorly defined insults by simulating a neoplasm.” In children especially it is important to be aware of this phenomenon, since some pediatric neoplasms are

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Inflammatory pseudotumors in buccal tissues of children J

rapidly proliferating mesenchymal lesions. In the head and neck region of children cellular vascular tumors, fibromatosis, and rhabdomyosarcomas are three of the more common tumors which could conceivably be confused with the inflammatory pseudotumor. So-called dental granulomas and traumatic eosinophilic granuloma of the gingiva, fibromatoid lesions of the gingiva, and reparative lesions of the tongue are processes of the oral cavity in which the histologic descriptions are very similar to the buccal lesions in our patients.*j. l6 One such case in a 6-month-old boy presented as a 2 cm. firm mass on the tongue, with surface ulceration.” The microscopic appearance in the underlying soft tissues was quite reminiscent of our cases. McDaniel and Marano’* emphasized the potential risk of a misdiagnosis of a malignant lesion. That pitfall is avoidable, but not completely so, as has been pointed out with regard to the fibrohistiocytic tumors, if careful note is taken of the polymorphous inflammatory reaction and the fibromyxomatous stroma. Clinically, the clinician should not be misled by the rapid growth of the lesion. There is a distinct risk of excessive overtreatment. The lesion can be expected to resolve completely and spontaneously. REFERENCES I. Bhaskar, S. N.: Oral Tumors of Infancy and Childhood. A Survey of 293 Cases, J. Pediatr. 63: 195-210, 1963. 2. Cozzutto, C., De Bemardi, B., Guarino, M., Cornelli, A., and Soave, F.: Retroperitoneal Fibrohistiocytic Tumors in Children: Report of Five Cases, Cancer 42: 1350-1363, 1978. 3. Weiss, S. W., and Enzinger, F. M.: Malignant Fibrous Histiocytoma: An Analysis of 200 Cases, Cancer 41: 22502266, 1978. 4. Allen P. W.: Nodular Fasciitis, Pathology 4: 9-26, 1972. 5. Wirman, J. A.: Nodular Fasciitis, a Lesion of Myofibroblasts: An Ultrastructural Study, Cancer 38: 2378-2389, 1976.

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6. Churg, A. M., and Kahn, L. B.: Myofibroblasts and related Cells in Malignant Fibrous and Fibrohistiocytic tumors, Hum. Pathol. 8: 205218, 1977. 7. Ramos, C. V., Gillespie, W., and Narconis, R. J.: Elastofibroma: A Pseudotumor of Myofibroblasts, Arch. Pathol. Lab. Med. 102: 538-540, 1978. 8. Pisciotto, P. T., Grav, G. F.. Jr.. and Miller. D. R.: Abdominal Plasma Cell Pseudotumor, J. Pediatr. 93: 628-630, 1978. 9 Buell, R., Wang, N.-S., Seemayer, T. A., and Ahmed, M. N.: Endobronchial Plasma Cell Granuloma (Xanthomatous Pseudotumor): A Light and Electron Microscopic Study, Hum. Pathol. 7: 41 l-426, 1976. 10. Bahadori, M., and Liebow A: Plasma Cell Granuloma of the Lung, Cancer 31: 191-208, 1973. 11. Greenberg, S. D., and Jenkins D. E.: Xanthomatous Inflammatory Pseudotumor of the Lung, South. Med. J. 68: 754-756, 1975. 12. Weiter J., and Farkas, T. G.: Pseudotumor of the Orbit as a Presenting sign in Wegener’s Granulomatosis, Surv. Ophthalmol. 17: 106-I 19, 1972. 13. Gonzalez-Crussi, F., Vanderbilt, B. L., and Miller, J. K.: Unusual Intracardiac Tumor in a Child: Inflammatory Pseudotumor of “Granulomatous” Variant of Myxoma? Cancer 36: 2214-2226, 1975. 14. Eversole, L. R., and Rovin, S.: Reactive Lesions of the Gingiva, J. Oral Pathol. 1: 30-38, 1972. 15. Zegarelli, D. J., Rankow, R. M., and Zegarelli, E. V.: A Dental Granuloma (? Inflammatory Pseudotumor) With Unusual Features: Report of Cases, J. Am. Dent. 89: 891-894, 1974. 16. Bhaskar, S. N. and Lilly, G. E.: Traumatic Granuloma of the Tongue (Human and Experimental), ORAL SURG 18: 206281, 1964. 17. Tornes, K., and Bang, G.: Traumatic Eosinophilic Granuloma of the Gingiva, ORAL SURG. 38: 99-102, 1974. 18. McDaniel, R. K., and Marano, P. ,D.: Reparative Lesion of the Tongue, ORAL SURG 45: 266-272, 1978. Reprint

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Dr. S. L. Liston Department of Otolaryngology A605 Mayo Memorial Building University Hospitals University of Minnesota Minneapolis, Minn. 55455