Translated Abstract
Background:
Orofacial granulomatosis (OFG) is a rare granulomatous diease characterized by recurring and permanent swelling and edema in orofacial and maxillofacial region. It was firstly named by Weisenfeld in 1985. It includes both Melkersson-Rosenthal syndrome (MRS) and granulomatous cheilitis (GC). Melkersson-Rosenthal syndrome refers to the clinical triad of swollen lips, fissure tongue and peripheral facial paralysis, accounts for only 13% of OFG. Granulomatous cheilitis refers to localized progressive swelling and hypertrophy of the lips.
The lesions of Orofacial granulomatosis are always specially located in orofacial regions. Therefore, it usually leads to tremendous physical and mental pain to the patient. However, it is actually not a very common disease and is still somehow great mystery and challenge to many physicians. And the exact cause of orofacial granulomatosis is unclear. Several factors including infection, delayed-type hypersensitivity, food allergies, genetic susceptibility and immune disorders have been reported to have potential connection with its pathogenesis. However, the opposite negative conclusions have also been reported in some other reports. So there is no definite conclusion about which factor directly determines the occurrence of the disease and how those various factors play roles together and influence each other to cause the disease. Moreover we are not clear about the mechanism of its clinical character of orofacial swelling.
Objectives:
1) To summarize clinical and pathological features of orofacial granulomatosis and to explore diagnostic criteria of it.
2) To analyze possible relationship between its clinical manifestation of swelling and formation of granulomas.
Methods:
1) Nineteen cases of orofacial granulomatosis were analyzed, their information including general information, possible etiology and incentives, course of disease, clinical symptoms and signs, pathological features were collected and retrospectively analyzed.
2) Paraffin-embedded tissue from their lesions were cut into slices and treated by immunohistochemical staining of CD68, CD31 and D2-40. And the results were carefully observed under a microscope to analyze the shape of blood and lymphatic vessels, the distribution of granulomas, and the relationship between granuloma and the shape of lymphatic and blood vessels.
Result:
1) General information and clinical characteristics of orofacial granulomatosis:
A total number of 19 cases of OFG were reviewed, including 7 males and 12 females, from 13 to 76 years old, with an average of 50.32 years. The disease course ranged from 2 months to 20 years, with an average of 33.62 months. 6 out of 19 cases had a history of dentures installation (31.58%), other possible incentives including gastritis, food allergies, oral infections and hyperthyroidism. The lips were the most frequently involved parts of OFG, which were found in all the 19 patients (100%), followed by tongue and cheek. 11 out of 19 patients had only lip involved and they were diagnosed as granulomatous cheilitis, and 4 out of 19 patients presented clinical triad of edema, facial paralysis and tongue folds and they were diagnosed as Melkersson-Rosenthal syndrome. Eight patients had two or even more lesions, and there was one patient had even four lesions, they are lips, periorbital region, tongue and buccal mucosa. The primary manifestation of OFG was persistent indurated edematous erythema with a small amount of scale on the surface, other signs include fissured tongue, hypertrophy of tongue, gingival hyperplasia, buccal mucosa thickening and ulceration.
2) Pathological results of orofacial granulomatosis.
In the HE staing of biopsies of lip from 19 cases of orofacial granulomatosis, tissue cells and lymphocyte predominant inflammatory cells were found forming non-caseating epithelioid granuloma in all specimens. Granulomas were mainly located in the superficial and middle layer of dermis in 13 out of 19 cases, restricted to the papillary layer in one case, and widely distributed from the papillary to the subcutaneous tissue layer in other five cases. That granuloma formed around or jajacent to lumens can be observed in all patients.
3) Immunohistochemical results of 19 cases of orofacial granulomatosis.
CD68 was strongly positive in all 19 cases, the positive cells including tissue cells and multinucleated giant cells, a large number of CD68-positive cells gathered in the granulomatous nodular area, and part of them were located within vessels. Granulomas’ formation around D2-40 positive lymphatic vessels were seen in 17 cases ( 89.47%). Granulomas’ formation within lymphatic vessels in and out of granulomatous area was seen in 13 cases(68.42%). Granulomas’ formation around CD31 positive blood vessels can also be found in 12 (63.15%) cases, however, different from lymphatic vessels there are just several scattered erythrocytes and lymphocytes within it, none histocyte, multinucleated giant cell or atypical cells were found.
Conclusion
1) Clinical features of orofacial granulomatosis.
Orofacial granulomatosis can occur both in men and women at any age, and it is clinically characterized by non-pitting persistent swelling. Lips were the most common involved part, other lesion sites including periorbital region, tongue, buccal mucosa, jaw and other lesion beyond orofacial region like vulva. Oral chronic infection may be the underlying cause of the disease.
2) Pathological features of orofacial granulomatosis
Orofacial granulomatosis is histopatholoically characterized by epithelial granuloma which is formed by aggression of large number of histocytes and lymphocytes. A small number of plasma cells, eosinophils and multinucleated giant cells can sometimes be also found. Granulomas were mostely frequently located in the supper or middle layer of dermis. Those granulomas were surrounding, adjacent to or within vessel structure.
3) Possible mechanism of localized swelling in orofacial granumatosis.
The formation of granuloma around or within lymphatic vessels leads to obstruction of lymphatic system, that drainage disorders in lymphatic system may be the underlying important mechanism of its localized swelling.
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