Clinical pathologic conference case 6: nonhealing extraction site

Abstract

Clinical Presentation

A 42-year-old male presents for a 5 week follow up appointment after extraction and bone graft of tooth #31. The area appeared to be healing normally at the 2 week postoperative appointment. The patient reported no significant medical history and a remote social history of smoking cigarettes.

At the initial appointment the patient reported pain for 4 weeks associated with tooth #31. Periapical radiograph (Figure 1) demonstrates a periapical radiolucency associated with the distal root and a radiolucency at the furcation. Clinical exam revealed a probing depth of greater than 7 mm on the facial/lingual aspect extending into the furcation and mobility of the tooth.

At the 5 week follow up appointment the patient reported a nonhealing extraction site and pain. Periapical radiograph (Figure 2) demonstrated a soft tissue enlargement with small radiopacities scattered in the soft tissue and residual extraction site. Clinical exam revealed an exophytic and ulcerated soft tissue mass in the area of #31 (Figure 3). Incisional biopsy of the soft tissue mass was performed at this appointment.

Differential Diagnosis

Prior to considering the postextraction clinical scenario, it is appropriate to comment on the pre-extraction presentation. Critical features to consider include the patient's report of pain along with the radiographic findings of an absence of caries, evidence of fracture or bone loss pattern associated with chronic periodontitis. Additionally, there is a loss of the lamina dura and asymmetrical widening of the periodontal ligament space. These findings, when considered in aggregate, raise the index of suspicion for malignancy. This will be discussed further as the overall postextraction differential diagnosis is considered.

This patient is presenting with an ulcerated soft tissue mass. Such a finding in the oral cavity could represent a long list of both reactive and neoplastic entities, in this case that list becomes shortened when taking into account the corresponding radiographic features.

Developing the differential diagnosis in this case it is important to consider the volume of bone observed radiographically at 5-weeks postextraction (Figure 2). Araújo and colleagues cite 3 months as the earliest point at which bone is observable on radiograph following exodontia,¹ suggesting that the bone present in this case is abnormal. This provides 2 possibilities for the presence of bone: (1) the bone graft placed at the time of extraction was not resorbed, or (2) the graft was resorbed, and the visible bone present at 5 weeks is neoplastic in origin.

Considering the first possibility, the bone graft may have failed due to any number of local factors including microbial colonization at the site. Hence, the radiographic bone could be the original graft material with the soft tissue mass representing an epulis granulomatosa. Epulis granulomatosa is a tumor-like growth of granulation tissue that may develop at extraction sites during the healing process.² It is also possible a neoplastic process was responsible for the patient's symptoms. In this case, a neoplasm may have disrupted the normal local immune function and inhibited graft resorption. Possible primary gnathic malignancies include squamous cell carcinoma derived from remnants of odontogenic epithelium and lymphoma.² Both entities can present with an ulcerated soft tissue mass, as well as the radiographic features observed. Although extremely rare, salivary gland neoplasms have been reported in the mandible yet the radiographic features are unlikely to align with what is seen in this patient.²

If the radiopaque material represents the formation of new bone, benign and malignant entities may be considered. The central ossifying fibroma (COF) is an uncommon benign tumor that occurs in the jaws over a broad age range.² While it produces bone, the typical radiographic finding is a well-defined lesion, unlike the scattered radiopacities seen in Figure 2. Furthermore, pain is uncommon with COF, and the bone volume at observed at the 5-week mark in this case suggests a high growth rate that is unlikely with a benign process.

Osteosarcoma is a bone-producing mesenchymal malignancy with a potential for rapid growth. It is known to present with a broad diversity of radiographic features.² A soft tissue mass is often present and this disease occurs in the 4th and 5th decades of life when primary to the gnathic skeleton. Several features in this case align with primary osteosarcoma, including the patient's experience of pain, and the preoperative radiograph showing a poorly defined radiolucency and asymmetrical widening of the periodontal ligament space (Figure 1).

While this patient's medical history was negative for prior malignancies, the possibility of an occult primary tumor metastasizing to the jaw, while unlikely, cannot be completely excluded³. The literature has documented several metastatic carcinomas that have osteogenic potential, including prostate, renal, lung and breast.^4-6

Diagnosis and Management

Incisional biopsy was submitted for histopathologic evaluation. Microscopic examination revealed ulcerated squamous mucosa overlying a diffuse infiltrate of intermediate-to-large round blue cells with focally vesicular chromatin and prominent nucleoli (Figure 4). Fragments of hard tissue consistent with bone graft material are seen scattered throughout the large round blue cells. Lesional cells were positive for CD20, CD10, BCL-6, and MUM1 (Figure 5). Ki-67 highlights an increased proliferation index at approximately 70%-80%. Additional immunohistochemical studies were performed and can be found in Table 1. Based on the immunohistochemical and histopathologic findings a diagnosis of large b-cell lymphoma, germinal center subtype was made. Fluorescence in situ hybridization studies were ordered and 3 copies of IGHG1 were found due to either rearrangements or copy number gain. No rearrangements of BCL6, MYC, or BCL2 were found.

This patient was subsequently referred to an outside hematology-oncology for treatment and management.

Discussion

Large b-cell lymphomas are a diverse group of tumors with variable genetic features, histomorphology, and clinical behavior. Classification of these tumors can be challenging with the largest diagnostic group being diffuse large b-cell lymphoma, not otherwise specified (DLBCL, NOS) comprising about 80% of diffuse large b-cell lymphomas.⁷ Tumors in this group do not fulfill diagnostic criteria for any other large b-cell lymphomas. In addition to DLBCL, NOS the most recent edition of the World Health Organization Hematolymphoid Tumors (5th ed) recognizes 17 unique large b-cell lymphomas that are characterized by specific genetic alterations as well as clinical context and location. About half of cases are diagnosed at Stage I or Stage II.⁸

Lymphomas affecting the head and neck are relatively common neoplasms, second in incidence to squamous cell carcinoma, and account for about 5% of all oral malignancies.⁹ The DLBCL, NOS group is genetically heterogenous, however, analysis for MYC, BCL2, and BCL6 rearrangements are clinically relevant due to the poor prognosis. Presence of double hit (BCL2/MYC or BCL6/MYC) or triple hit (BCL2/BCL6/MYC) rearrangements results in an extremely poor prognosis.¹⁰ While the current case was positive for BCL6 and MUM1 on immunohistochemistry, genetic testing found no rearrangements of BCL2, MYC, or BCL6.

Current treatment for large b-cell lymphomas is R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone with rituximab) therapy, which has significantly improved survival rates. The 5-year overall survival rate for patients with diffuse large b-cell lymphoma , germinal center subtype is estimated at 60% following R-CHOP.¹¹

This case highlights the importance of biopsy in suspicious lesions in the oral cavity and the rapid growth that oral lymphomas can demonstrate.