Plasma cell granulomas (PCGs) are uncommon, non-neoplastic lesions of unknown etiology and are considered an entity of IgG4-related diseases. History/Introduction PCGs were first discovered and described in 1973 by Bahadori and Liebow. PCGs are characterized by the proliferation and infiltration of different inflammatory cells with the main cell observed in highest concentrations being plasma cells. More specifically, PCGs are a type of mass-forming lesion arising from the accumulation of polyclonal plasma cells surrounded in a swirling storiform orientation of fibrosis and spindle cell proliferation. It has been noted that these granulomas have the propensity to manifest on any organ or soft tissue. Plasma cell granulomas are generally found to be benign, but in some cases, the granulomas have the ability to initiate malignancy and become symptomatic regardless of location or size. Common sites of plasma cell granulomas are in the oral gingiva, lungs, vagina, larynx, orbit, spinal cord meninges, breast, pelvic soft tissue, bladder, mesentery, retroperitoneum, kidney, lymph nodes, spleen, pancreas, liver, stomach, heart, thyroid, and trachea. Microscopically, plasma cell granulomas, demonstrate a lesional pattern of inflammatory pseudotumor. The term inflammatory pseudotumor has previously been used to classify plasma cell granulomas. However, this term has become more uncommon in recent years due to its lack of specificity. Today, scientist use more up to date diagnostic and medical terminology to avoid classifying lesions in the same group that are likely to have different etiologies. Other names associated with plasma cell granulomas are inflammatory myofibroblastic tumor, inflammatory myofibrohistiocytic tumor, benign myofibroblastoma, pseudosarcoma, fibrous histocytoma, fibroxanthoma, xanthomatous pseudotumor, xanthogranuloma, myxoid hamartoma, and lymphoid hamartoma. Etiology The etiology of plasma cell granulomas is widely unknown, however, there are a few ideas on what causes the condition to develop. Studies suggest that one possible causative factor is the presence of a foreign body. A foreign body is likely to give off an antigenic cue causing the accumulation of polyclonal IgG4 positive plasma cells. Others suggest that plasma cell granulomas have an autoimmune origin. PCGs have also been found to be drug and/or hormone induced. Pathology Diagnosis/Differentiation Since plasma cell granulomas have the ability to occur at any site, even though they are uncommon, it should be included in differential diagnostics in regard to plasma cell neoplasms. With granulomas that arise in the mouth, PCGs are commonly misclassified considering the malignancy of the disease due to its aggressive behavior and clinical presentation. Plasma cell granulomas located