Case Report
Thymic Carcinoma Metastatic to the Mandible Mistaken for Medication-Related Osteonecrosis of the Jaw: A Case Report and Review of the Literature
Lee CYS1*, Rahman M2, Lee KL3 and Hirata KY4
*Corresponding author: Cameron YS Lee, Department of Periodontology and Oral Implantology, Temple University, USA
Published: 02 Aug, 2018
Cite this article as: Lee CYS, Rahman M, Lee KL
Hirata KY. Thymic Carcinoma
Metastatic to the Mandible Mistaken for
Medication-Related Osteonecrosis of
the Jaw: A Case Report and Review of
the Literature. Clin Surg. 2018; 3: 2060.
Abstract
Thymic tumors usually metastasize locally to the liver, lung, bone and brain. Thymic carcinoma
metastasizing to the mandible is a rare occurrence. This case report describes metastatic thymic
carcinoma that was presumed to be medication-related osteonecrosis of the jaw after extraction of
a molar tooth. To our knowledge, there have been no reported cases of metastases from the thymus
gland to the mandible in the medical and dental English literature. We report a case of metastatic
thymic carcinoma to the mandible that was mistaken for Medication-Related Osteonecrosis of the
Jaw (MRONJ).
Keywords: Thymic carcinoma; Extrathoracic metastasis; Medication-related osteonecrosis of the mandible (MRONJ)
Introduction
Metastatic carcinoma of the jaws represents 1% of all malignancies of the oral cavity [1-3]. The
mandible is the primary anatomic site of metastases [4]. In women, metastasis has been reported to
occur from distant sites such as the breasts, kidneys, genitals, colorectal region and thyroid gland. In
men, they can metastasize from the lungs, kidneys, prostate gland, and colorectal region [1,5,6-8].
Metastasis via vascular dissemination from abdominal organs to the oral and maxillofacial region is
considered rare because malignant cells must circulate through organs such as the lung and liver
[9]. To the best of our knowledge, there have been no reported cases of extrathoracic metastases
from the thymus gland to the mandible. We present a case of metastatic thymic carcinoma to the
mandible that was mistaken for medication-related osteonecrosis of the jaw (MRONJ).
Thymic neoplasms are rare tumors of the anterior mediastinum with an incidence estimated
at 1 to 3 cases per 10 million individuals [10,11]. Thymic carcinoma is usually diagnosed during
the fifth to seventh decade of life. Although most metastatic sites were not biopsied and histology
not available, Ichino et al. [12] was able to document 83 cases of extrathoracic metastasis from the
thymus gland. In a more recent study, Huang and colleagues [13] described 120 cases of thymic
tumors treated at Memorial-Sloan Kettering Cancer Center from 1995 to 2006. Of the 120 patients,
eight developed extrathoracic metastatic thymic carcinoma. As in the previous study, this was not
confirmed histologically, as all 8 patients did not complete biopsy procedures. However, in review
of thirty-five cases of extrathoracic metastasis of thymus origin, liver and lymph node were the most
frequent metastatic sites and 9 cases were biopsy positive for lymph node metastasis [14].
Thymic tumors are derived from thymic epithelium of the thymus gland, which is important
in childhood immunity. In adults, the gland is still present, but in an atrophic state [15,16]. It is the
most common tumor of the anterior mediastinum in adults [11,17]. Patients with thymic carcinoma
may have any of the following clinical symptoms: chest pain, back pain, dyspnea, voice changes,
cough, dysphagia, and fatigue and weight loss [18]. Rarely, polymyositis or dermatomyositis are
observed in the patient with thymic carcinoma [19-21]. There are two types of tumors derived from
the thymus gland, thymomas and thymic carcinoma. Thymomas make up about 50% of tumors
of the anterior mediastinum. Thymic carcinoma is a rare malignancy and accounts for 5% of all
malignancies of thymic origin. Compared to thymoma, thymic
carcinoma has a greater metastatic potential and invasiveness that
result in a poor prognosis [22-25]. Of the 11 different subtypes
recognized by the 2004 World Health Organization classification,
squamous cell carcinoma is the most common subtype and accounts
for up to 40% of reported cases. Histologically, it is undistinguishable
from carcinoma from other organs [22,26-28].
Figure 1
Figure 1
Panoramic radiograph showing osteolytic lesion with ill-defined
margins and what appears to be bone fragments in the right posterior
mandible.
Figure 2
Figure 2
Axial cone beam CT scan reveals osteolytic lesion with erosion of
the buccal cortex of the right posterior mandible.
Case Presentation
In January 2017, a 74-year old Asian female was referred from
her dentist for a non-healing extraction site. A molar tooth of the
right posterior mandible that was extracted in October 2016 due
to mobility and pain. One month after the tooth extraction, the
dentist performed a local curettage for a post-operative infection.
As the infection failed to resolve and was unresponsive to antibiotic
therapy, the family dentist was concerned about the possibility of
medication-related osteonecrosis of the jaw. The patient was treated
for osteoporosis for greater than 5 years with the bisphosphonate
drug, fosamax (70 mg/week) for osteoporosis. At the time of clinical
presentation, the patient was also diagnosed with stage IVb thymic
carcinoma (Masaoka staging system) and treated with combination
systemic chemotherapy consisting of carboplatin (300 mg/m2/
day) and paclitaxel (200 mg/m2/day) every three weeks. Panoramic
radiograph revealed a mixed radiolucent-radiopacity in the area of
the extraction site (Figure 1). The patient reported that there was
a constant aching pain in the right posterior mandible that failed
to resolve by both narcotic and non-steroidal over the counter
medications after the molar tooth was extracted by her dentist. She
also reported a history of paresthesia over the skin of the right chin
and right lower lip. Based on the patient’s medical history and clinical
findings, metastatic disease to the mandible could not be excluded.
The differential diagnosis included medication-related osteonecrosis
of the mandible, osteomyelitis and thymic carcinoma metastatic to
the mandible.
The patient’s medical history was significant for osteoporosis,
hyperlipidemia, depression and stage IVb thymic carcinoma diagnosed
in January 2015 by supraclavicuar lymph node biopsy. At the time
of presentation, the anterior mediastinal tumor was inoperable. No
allergies to medication were reported by the patient. She was a former
for 20 years who quit in 1980. Physical examination revealed
a female in mild distress from the chronic, unrelenting pain in the
right mandible. No facial swelling, asymmetry or orocutaneous fistula
was observed. Cranial nerve examination revealed a V3 paresthesia
over the skin of the right chin and right lower lip. Head and neck
examination was positive for lymphadenopathy.
Oral examination of the right posterior mandible revealed teeth
#30 and 32 missing. The gingival tissues in the area of missing tooth
#30 were edematous and erythematous with signs of inflammation.
Purulent discharge was observed from the non-healing extraction
site. No exposed bone was observed in the extraction site. Cone
beam CT scan revealed an osteolytic lesion with destruction of the
buccal cortical plate of the right posterior mandible (Figure 2).
Under local anesthesia, the extraction site was debrided of non-vital
necrotic osseous and granulation tissue under local anesthesia. The
tissue specimens were sent to the laboratory for histopathologic
examination.
Histopathology
Decalcified sections of bone from the right posterior mandible
revealed devitalized bone infiltrated by nests of neoplastic cells
associated with a desmoplastic response. Tumor cells demonstrated
atypical enlarged nuclei with prominent nucleoli. Occasional mitotic
figures were observed (Figure 3A and 3B). The results are consistent
with squamous cell carcinoma of the mandible and are similar to a
supraclavicular lymph node biopsy performed at another medical
center.
Immunohistochemistry
Immunohistochemical analysis revealed that the neoplastic cells
stained immunopositive for p40 (Figure 4A) and CD5 (Figure 4B).
Figure 3
Figure 3
Histopathologic analysis of specimen from right mandible
(hematoxylin and eosin stain). 3A: Lower power view (original magnification
x 10) shows infiltration of large islands of polygonal neoplastic cells of varying
size. 3B. High power view (original magnification x 20) shows bone infiltrated
by neoplastic epithelial cells with enlarged nuclei, marked pleomorphism,
eosinophilic glassy cytoplasm and hyperchromasia.
Figure 4A and 4B
Figure 4A and 4B
Immunohistochemical analysis of specimen from right
mandible. Neoplastic cells are positive for p40 and CD5 suggestive of
squamous cell thymic carcinoma metastatic to the mandible.
Discussion
Bisphosphonates are the cornerstone in the management of
osteoporosis and prevention of skeletal related events [29-31]. Patients
prescribed bisphosphonates who complete surgery that involves the
jaw bones are at risk for developing MRONJ. They may experience
delayed wound healing that results in dehiscence of soft tissues with
exposed necrotic bone, pain, infections involving both hard and soft
tissues of the affected area and altered neurosensation [32-35].
There have also been reports of patients treated with the cancer
medications carboplatin and paclitaxel that may develop MRONJ.
Wang et al. [36], reported three cases of osteonecrosis of the jaw
associated with systemic cancer chemotherapy for metastatic
breast cancer. The risk of developing osteonecrosis of the jaws is
approximately 1% for patients treated with both drugs [37,38].
Paclitaxel is an antimicrotubulin agent that binds to microtubules
during mitosis and prevents cell division in malignant and normal
cells [39]. Such antitumor effect at the cellular level may lead to
osteonecrosis. Carboplatin is a derivative of the chemotherapy cancer
alkylating agent, cispalatin [37,40]. It binds to DNA and inhibits
synthesis by cross-linking the DNA strands. Such action results in
cell death. Cancer polychemotherapy is the standard of care, as both
drugs have their primary effect at different phases of the reproductive
cell cycle.
Because metastatic lesions to the oral cavity are rare and may
be mistaken for MRONJ, they can pose a diagnostic challenge [41-
43]. Bedogni et al. [44] reported two cases that were mistaken for
MRONJ based on medical history, clinical and radiographic findings.
In both cases, biopsy of the jaw was not performed and the patients
underwent surgical resection of the jaw because of failure to resolve the
osteonecrosis with antibiotic treatment and constant pain. In our case,
thymic carcinoma metastatic to the mandible was also a diagnostic
challenge as the clinical and radiographic signs and symptoms were
not pathognomonic for MRONJ. Therefore, the authors recommend
that incisional biopsy for histopathologic analysis be routinely
performed in patients with documented malignancy [11,41-46,47].
Based on the medical history of stage IVb thymic carcinoma,
no exposed bone observed and that our patient was experiencing
paresthesia of the right lower lip and chin, metastatic disease was an
important consideration in the differential diagnosis even though
she was referred by her dentist for suspected MRONJ. Altered
neurosensory function involving the chin and lower lip is considered
a major clinical symptom of metastatic disease to the oral cavity [48-
50].
Clinical signs and symptoms of metastatic lesions of the oral
cavity are similar to MRONJ and may include edema, erythema, pain,
mobility of teeth, soft tissue masses, pathologic fractures and altered
neurosensation [1,6,51-53]. The clinician must always be aware that
MRONJ and metastatic lesions to the oral cavity have many similar
pathognomonic radiographic signs [41,42,44,47]. In an analysis of 390
cases, Hirshberg et al. [54], discovered that 5.4% did not demonstrate
any radiographic changes suggestive of metastatic disease to the jaws.
In a retrospective study of 114 metastatic tumors in the jaws, D’Silva
and colleagues [7], reported that no radiographic evidence was
detected in 5% of the cases studied. However, intraosseous carcinoma
on computed tomography may appear as a homogenous mass with
irregular borders and bone destruction [55].
Although treatment of thymic carcinoma is beyond the scope
of this case report, it is important to realize that the prognosis of
metastatic lesions to the oral cavity usually have a poor prognosis
[56]. In a Japanese study, 46.5% of patients with stage IVb thymic
carcinoma have more advanced disease at the time of presentation and
therefore, are unresectable compared to patients that are diagnosed
with stage IV thymoma [57]. Such poor prognosis is usually due to
a delay in the initial diagnosis [2,3,25,27]. The 5-year survival rate is
less than 10% [25,58,59]. At the time of presentation, our patient had
already been diagnosed at an advanced tumor stage with metastases
to the liver and skeleton. The patient expired five months later after
the biopsy procedure of the mandible.
In the evaluation of the patient with metastatic thymic disease,
it is important to rule-out other neoplasms [46,60]. The differential
diagnosis of metastatic squamous cell thymic carcinoma to the jaw
should include metastasis from other mediastinal organs such as the
lung and esophagus. Because there is no current immunohistochemical
marker for thymic carcinoma and the morphologic variation of this
neoplasm, exclusion of metastatic disease from the thymus gland
must rely on clinical and imaging studies, and examination of biopsy
samples when available. For the patient with an anterior mediastinal
mass, clinical symptoms described earlier and no tumor discovered in
another part of the patient, thymic carcinoma must be included in the
differential diagnosis [14].
Conclusion
This case report emphasizes the importance of obtaining a careful medical history in addition to a thorough clinical examination. This is especially with the patient that presents with presumed medicationrelated osteonecrosis of the jaws but has a significant medical history of metastatic disease. Imaging studies such as plain radiographs and computed tomography are not specific for either MRONJ or metastasis to the jaws. For a definitive diagnosis for either pathologic entity, we recommend routine incisional biopsy for histopathologic examination of all patients with metastatic disease.
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