Introduction

Inflammatory myofibroblastic tumor (IMT) is a rare reactive, non-neoplastic tumor-like lesion of predictably, unknown etiology. It consists of a variable admixture of inflammatory cells, including mature lymphocytes, histiocytes, plasma cells and eosinophils, with infiltrates of collagen fibrils. The major histological finding is that of a chronic inflammatory cell infiltrate, predominantly composed of polyclonal plasma cells. Plasma cell granuloma, as inflammatory myofibroblastic tumor (IMT) was formerly recognized as, was first reported by Brunn in the lungs in 1939. In 1968, Bhasker, Levin and Firch were the first to report such a case in the gingival tissues (Bhaskar et al., 1968).  Plasma cell granuloma was first described as a specific entity by Bahadori and Leibow in 1973 (Son et al., 2010). Various synonyms used for it include inflammatory myofibrohistiocytic tumor, inflammatory pseudotumor, xanthomatous pseudotumor, plasma cell granuloma, myxoid hamartoma, lymphoid hamartoma, fibrous xanthoma, benign myofibroblastoma, pseudosarcoma and most recently, inflammatory myofibroblastic tumor (IMT) (Anila et al., 2008). Plasma cell granuloma is a relatively uncommon lesion with most of the cases reported in the lungs which are the most common site of involvement although it, might, also, be seen in relation to other visceral organs including brain, kidney, stomach, and heart (Urschel et al., 1992). In the head and neck region, it is seen primarily in relation to oral mucosa (Ide et al., 2000), temporal bone (Nam et al., 1994), tonsillar region (Weilbaecher and Sarma, 1984), submandibular region (Inui et al., 1993), paranasal sinuses (Toriumi et al., 1987), tongue (Soares et al., 1987), and gingival (Acevedo and Buhler, 1977) and periodontal tissues (Ronald and Kuppersmith, 1996). The exact etiology is still unknown but hypotheses suggest that it might be seen due to a focus of irritation or, an impacted foreign body or, an idiopathic, antigenic stimulation. The common microorganisms associated with the lesion include mycobacteria, Epstein barr virus, actinomycetes, nocardia, and mycoplasma etc. Clinically, plasma cell granuloma presents as a nodular, polyploidal mass with a relatively smooth surface. It remains asymptomatic until it reaches a sizeable dimension wherein it might get secondarily ulcerated and infected in cases of trauma. Histopathological examination of the lesion reveals plump spindle cells admixed with chronic inflammatory cell infiltrates in a richly vascular myxomatous stroma. The most common treatment accepted for plasma cell granulomas is surgical excision and/or, complete resection. Other treatment modalities include radiotherapy and steroids, which have, also, been used successfully to treat larger, non-resectable lesions in case they assume greater dimensions, are in close proximity to vital structures in the area or, are deeply seated or, infiltrating to the adjacent and subjacent tissues (Neville et al., 2002).

Case Report

A 52 year old male patient (Figure 1) reported with a chief complaint of an enlarging but painless, gingival growth in relation to upper front tooth region (Figure 2). The growth was present since two years and was slowly increasing in size. There was no history of trauma and/or, surgery to the concerned region. There were no systemic symptoms and medical history of the patient was not significant either. On examination, the growth was polyploidal, nodular, firm, non-tender and with regular and non-indurated borders measuring around 1.5×0.8 cms in dimensions and appeared to be arising from the inter-dental gingiva in 11 and 12 region with no evidence of tooth mobility or, displacement. The growth was not seen to be extending till the palatal aspect. Intra-oral periapical radiograph (IOPAR) did not reveal any bony involvement (Figure 3) and routine laboratory investigations were found to be normal. Based on the said history and clinical features, a provisional diagnosis of pyogenic granuloma was arrived-at. The differential diagnoses included peripheral ossifying fibroma, giant cell epulis, neurofibroma, peripheral giant cell granuloma and capillary hemangioma to add to the list in the end. The growth was surgically excised (Figure 4) and subjected to histopathological examination. Histopathological examination revealed a dense fibrovascular connective tissue with sheets of mixed inflammatory cell infiltrates comprising of plasma cells and lymphocytes with intervening osteoid matrix and few blood vessels with extravasated red blood cells and an overlying parakeratinized stratified squamous epithelium with anastomosing rete pegs. (Figure 5). The tissue was, also, subjected to immunohistochemical analysis. Immunohistochemical examination revealed kappa and lambda light chain immunoglobulin markers which are used to differentiate reactive from benign and malignant lesions as was confirmed in our case with a positive reaction revealing the lesion to be reactive rather than being benign or, malignant in nature (Figure 6). Also, CD-68 antibody marker was used which is used to differentiate benign from malignant lesions and it came-out to be negative in our case, thereby, further confirming our diagnosis to go in favor of a purely reactive and non-neoplastic lesion (Figure 7). Based on the above findings, a final diagnosis of plasma cell granuloma of gingiva was confirmed. The patient was re-called after 3 months for a follow-up when the examination revealed no clinical evidence of any possible recurrence (Figure 8).

Discussion

Inflammatory myofibroblastic tumor (IMT) and/or, Plasma cell granuloma, as it was formerly called as, was re-named, so, in the recent revision in nomenclature due to its heavy content of lymphoid and plasmacytic elements. In 1952, Zoon first described phenomenon of plasma cell infiltrates in Balanitis plasma cellularis (Aiba and Tagami, 1989). Later, during the late 1960’s and early 1970’s, cases of plasma cell infiltrates of tongue, gingiva and lips were described under the names idiopathic gingivostomatitis, atypical gingivostomatitis and allergic gingivostomatitis. Plasma cell granuloma is a rare tumor-like, reactive, proliferative lesion, consisting predominantly of plasma cells occurring in a broad age range and tends to affect more often children and young adolescents. No distinct radiographic changes are reported in most of the cases except for some which show infiltrative margins. Such lesions have an even rare occurrence in the head and neck region and when reported, are more commonly seen in adults with a definite male predisposition. In the head and neck region, inflammatory myofibroblastic tumors (IMTs) are most commonly seen in relation to the larynx, especially in the region of true vocal cords; the other common areas of involvement include the oral cavity, tonsils, para-pharyngeal spaces, sino-nasal tract, salivary glands and trachea. Corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs) have been successfully used for the treatment resulting in regression in most of the patients. IMTs were originally believed to be reactive, non-neoplastic lesions, although, few cases might be seen in the form of aggressive lesions and there are few reported cases of metastasis in the IMTs seen outside the head and neck region. This makes it even more obvious for the need for a detailed clinical and histopathological follow-up even after the lesions are excised, although, sometimes, the histopathological reports have, too, been found to be misleading in terms of declaring a lesion to be towards an aggressive clinical course. The myofibroblasts invariably maintain a low nuclear-to-cytoplasmic ratio. Focal nuclear pleomorphism may be present. Abnormal mitosis is common, sometimes, even abundant, but never showing atypical mitotic figures. Necrosis and marked nuclear pleomorphism are not seen, hence, IMTs are not considered as true neoplasms. In oral cavity, inflammatory myofibroblastic tumors (IMTs) and/or, plasma cell granulomas tend to occur more commonly in relation to the periodontal tissues and these lesions represent oral counterparts of cutaneous angio-plasma-cellular hyperplasias (Fumio et al., 2000). Kim et al reported gingival plasma cell granuloma in a patient with cyclosporine-induced gingival overgrowth and suggested that Interleukin-6 (IL-6) and phospholipase C-γ1 may induce plasma cell infiltrates in cyclosporine-induced gingival overgrowths (Kim et al., 2002). Roman hypothesized in literature that plasma cell granuloma might be associated with low levels of serum and secretory IgA which results in localized repetitive sub-clinical infections that lead to plasma cell infiltrations (Roman et al., 2002). Dalrymple and Henry Bence-Jones first described neoplastic proliferation of plasma cells in 1846 characterized by marked proteinuria and bone pains. Tumors which consist of plasma cells include multiple myeloma, solitary myeloma, plasmacytoma and plasma cell granuloma. Multiple myeloma and solitary myeloma are bone tumors where as plasmacytoma and plasma cell granuloma are soft tissue tumors. It is important to distinguish plasma cell granuloma from extra-medullary plasmacytoma, multiple and solitary myeloma as the latter ones have poorer prognosis. Plasmacytoma is a well-defined, locally destructive lesion located on the mucosa of oro-pharyngeal region. Histologically, they have typical and atypical plasma cells unlike plasma cell granulomas which contain normal plasma cells and small lymphocytes surrounded by connective tissue septa and Russel-Fuchs bodies (Nam et al., 1994). Immunohistochemistry determines clonality of the lesion which is done to rule-out malignancy in the lesion. It is based on kappa-lambda light chain gene re-arrangements. In reactive lesions, kappa to lambda light chain ratio is 2:1 and in case of malignant counterparts, this ratio may exceed to 10:1. (Peacock et al., 2001) It is generally considered that lesions consisting of monoclonal plasma cells are neoplastic and polyclonal plasma cells are inflammatory. Recurrence rates are reported to be in a range of 24-40% (Wood and Goaz, 1996). A correct recognition of the lesion, therefore, becomes all the more important to avoid needless, extensive and radical surgical procedures which leave the patient with considerable morbidity.

Conclusion

Inflammatory myofibroblastic tumor (IMT) and/or, Plasma cell granuloma, as it was formerly called as, of gingiva is a rarely reported peripheral soft tissue lesion that might be confused with a malignant mesenchymal tumor on clinical and radiographic investigations. The histopathological appearance which is similar to other common oral spindle cell tumors, also, leads to the fear of it being a more aggressive, rather, a neoplastic lesion. The exact idea of this clinical entity with its distinctive morphological features and with a rare occurrence, therefore, becomes even more significant in avoiding the possibility of a wrong impression of being a neoplastic lesion. It is, also, important to recognize this entity as a benign inflammatory lesion which is primarily reactive in nature to avoid extensive and potentially destructive surgery. With this background, this case report presents one of such rare cases with a distinct clinical entity of a gingival pathology that mimicked a neoplastic condition.

References

Acevedo A, Buhler JE. Plasma-cell granuloma of the gingiva. Oral Surg Oral Med Oral Pathol 1977, 43:196-200.

https://doi.org/10.1016/0030-4220(77)90156-6

Aiba S, Tagami H. Immunoglobulin-producing cells in plasma cell oro-facial mucositis. J Cutan Pathol 1989, 1:207-210.

https://doi.org/10.1111/j.1600-0560.1989.tb00042.x

Anila Namboodripad PC, Jaganath M, Sunitha B, Sumathi A. Plasma cell granuloma in the oral cavity. Oral Surg 2008, 1:206-212.

https://doi.org/10.1111/j.1752-248X.2008.00034.x

Bhaskar SN, Levin MP, Firsch J. Plasma cell granuloma of periodontal tissues: Report of 45 cases. Perio 1968, 6:272-276.

Fumio I, Tetsuo S, Norio H. Plasma cell granuloma of the oral mucosa with angiokeratomatous features: A possible analogue of cutaneous angioplasmocellular hyperplasia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000, 89:204-207.

https://doi.org/10.1067/moe.2000.103127

Ide F, Shimoyama T, Horie N. Plasma cell granuloma of the oral mucosa with angiokeratomatous features: A possible analogue of cutaneous angioplasmocellular hyperplasia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000, 89:204-207.

https://doi.org/10.1067/moe.2000.103127

Inui M, Tagawa T, Mori A, Yoneda J, Nomura J, Fukumori T. Inflammatory pseudotumor in the submandibular region. Clinico-pathologic study and review of the literature. Oral Surg Oral Med Oral Pathol 1993, 76:333-337.

https://doi.org/10.1016/0030-4220(93)90263-4

Kim SS, Eom D, Huh J, Sung I, Choi I, Sung HR, et al. Plasma cell granulomas in cyclosporine-induced gingival growth: A report of two cases with immunohistochemical positivity of Interleukin-6 and Phospholipase C. J Korean Med Sci 2002, 17:704-707.

https://doi.org/10.3346/jkms.2002.17.5.704

Nam BH, Rha KS, Yoo JY, Park CI. Plasma cell granuloma of the temporal bone: A case report. Head Neck 1994, 16:457-459.

https://doi.org/10.1002/hed.2880160512

Neville BW, Doliglas D, Carl M, Jerry E. Hematologic disorders. In: Neville BW, Doliglas D, Carl M, Jerry E, editors. Oral and Maxillofacial Pathology. 2nd ed. Philadelphia: Saunders; 2002. p. 526-527.

Peacock ME, Hokett SD, Hellstein JW, Herold RW, Matzenbacher SA, Scales DK, et al. Gingival plasma cell granuloma. J Periodontol 2001, 72:1287-1290.

https://doi.org/10.1902/jop.2000.72.9.1287

Roman CC, Yuste CM, Gonzalez MA, Gonzalez AP, Lopez G. Plasma cell gingivitis. Cutis 2002, 69:41-45.

Ronald B, Kuppersmith MD. Extra-medullary plasmacytoma of the head and neck. Grand Round Archive, Baylor College of Medicine, Houston, TX. 1996.

Soares J, Maura Nunes JF, Sacadura J. Plasma cell granuloma of the tongue: Report of a case. Histol Histopathol 1987, 2:199-201.

Son SB, Heo YS, Shin WW, Oh TS, Song HJ, Oh CH. A Case of Cutaneous Inflammatory Myofibroblastic Tumor. Ann Dermatol 2010, 22:91-95.

https://doi.org/10.5021/ad.2010.22.1.91

Toriumi DM, Sykes JM, Wolff AP, Goldschmidt RA. Plasma cell granuloma of the paranasal sinuses. Otolaryngol Head Neck Surg 1987, 96:562-564.

https://doi.org/10.1177/019459988709600608

Urschel JD, Horan TA, Unrach HW. Plasma cell granuloma of the lung. J Thorac Cardiovasc  Surg 1992;104:8705.

Weilbaecher TG, Sarma DP. Plasma cell granuloma of tonsil. J Surg Oncol 1984;27:228-231.

https://doi.org/10.1002/jso.2930270406

Wood NK, Goaz PW. Differential Diagnosis of Oral and Maxillofacial Lesions. St. Louis: The CV Mosby Co.; 1996. p. 385.