Discussion

Prostate cancer is the second most common cancer in men, accounting for 1 in 9 of all new cancers, and with more than 670,000 new diagnoses worldwide annually (9). The metastatic spread is primarily in the axial skeleton in which lesions are often located in vertebra and ribs via dissemination through Batson's venous plexus. The spread in bone also follows the distribution of adult red bone marrow, that is skull, thorax, pelvis, spine, proximal long bones (10,11), subsequently progressing to involve adjacent cortical bone.

Although metastatic prostate carcinoma is predominantly osteoblastic (bone forming type), osteoclast activation also has an important role in the growth of sclerotic metastasis in bones. In a study of 68 patients with prostatic bone metastasis who underwent surgery for stabilization of pathological fracture or impending fracture, most lesions were osteoblastic and only 29.1% were osteolytic or mixed (12).

Histopathologic analysis of metastatic prostate tumors typically shows substantial numbers of osteoblasts adjacent to prostate cancer cells, whereas few or no osteoblasts can be seen in normal bone or in metastatic bone lesions from other types of cancers (kidney, lung, and most cases of breast cancer) in which most often exist plenty of osteoclasts in cancer-affected areas. Increased osteoblast activity in metastatic prostate cancer lesions of bones is accompanied by elevated serum level of osteoblast proliferation markers such as bone-specific alkaline phosphatase in the affected patients similar to the reported cases here (13).

Skeletal metastases occur in approximately 90% of patients presenting with advanced prostate cancer and the extent of bone disease directly correlates with survival (14, 15); however, Metastasis to jaw bones is uncommon. The identification of these lesions can become a real diagnostic challenge because they present non-specific symptoms. Nevertheless, they have a diagnostic (a quarter of them reveal unknown cancer) and prognostic significance (their presence is correlated with limited survival of the patient) (7, 16).

In an extensive review of metastatic tumors to jaw bones, Hirshberg et al. observed that the most common primary cancer site was breast, followed by lung, adrenal, kidney, bone, colorectal and prostate (17). In accordance with results from other studies, they also showed that the most common site of metastatic tumors was the mandible (85%) and only 13.6% of the metastatic tumors happened in maxilla (5, 17, 18, 19).

In most patients who present with a metastatic tumor, as in our second case, the distant primary tumor has already been diagnosed, and in most cases treated. However, as in our first case, the discovery of a metastatic tumor leads to detection of an occult primary malignancy elsewhere in the body (17, 19, 20). In such cases, the histopathologic features of the metastatic tumor may provide an evidence for detection of primary tumors.

Compatible with other authors’ descriptions, our first patient's chief complaints were swelling, ill-fitting denture, pain, trismus and paresthesia (5, 17, 21, 22). Metastatic Prostate cancer tends to be osteoblastic and leads to make the surrounding bone thicker and denser, whereas many other metastatic cancers to the bones tend to be osteolytic. The metastatic deposits of prostate cancer cells in the mandible around the inferior alveolar nerve can cause pain and paresthesia characterized as numb chin syndrome (NCS) (23, 24).

Although most cases of NCS are of benign origin (e.g., dental disease, dental anesthesia or trauma, diabetes mellitus, sarcoidosis, multiple sclerosis, amyloidosis or osteomyelitis), in the absence of trauma or dental history, especially in elderly people, malignancies must be included in the differential diagnoses of NCS (24,25).

Systemic diseases such as diabetes mellitus, lupus erythematosus or sarcoidosis usually present as mononeuropathy multiplex, not as numbness restricted to the distribution of the mental nerve. Giant cell arteritis is another unusual cause of NCS (26).

On the other hand, metastasis to temporal bone typically presents with the classical triad of otalgia, periauricular swelling and facial nerve palsy (27). Also, increased bone volume due to metastatic lesion, in some cases, can lead to trismus (5, 17, 22).

Detection of an asymptomatic metastatic disease in prostate cancer is greatly affected by the staging tests performed. Radionuclide bone scans are currently the most widely used tests for metastases to bone, which is the most common site of distant tumor spread. Magnetic resonance imaging (MRI) is more sensitive than radionuclide bone scans but is impractical for evaluating the entire skeletal system.

Some evidence suggests that serum PSA levels can predict the results of radionuclide bone scan in newly diagnosed patients. In one series, only 2 of 852 patients (0.23%) with a PSA of less than 20 µg/l, had a positive bone scan in the absence of bone pain (28). In another series of 265 prostate cancer patients, 0 of 23 patients with a PSA of less than 4μg/l, had a positive bone scan, and 2 of 114 patients with a PSA of less than 10 μg/L had a positive bone scan (29).

Detection of bone metastases indicates progression to lethal prostate carcinoma (30). At this stage, complete remissions are rare and onset of complications of bone metastases is likely. Survival of the patient with prostatic carcinoma is related to the extent of tumor. When cancer is confined to the prostate gland, median survival in excess of 5 years can be anticipated. Patients with locally advanced cancer are not usually curable and a substantial fraction will eventually die of the tumor, though median survival may be as long as 5 years. If prostate cancer has spread to distant organs, current therapy will not cure it. Median survival is usually 1 to 3 years and most such patients will die of prostate cancer (31).

In the two reported cases, in addition to hormonal therapy, local treatment of mandibular metastasis was performed by radiotherapy, which usually subsides pain and functional loss. Even in this group of patients, however, indolent clinical courses lasting for many years may be observed, but finally, death from cancer is inevitable.

Conclusion:

Although rare and with atypical symptoms, metastatic urogenital malignancies have been shown in jaws and cranium. A hamatogenous mechanism for spread from the primary site has been postulated and widely accepted. So, unusual symptoms such as a recently ill-fitting denture, chin numbness or generalized musculoskeletal pain should be considered the result of metastasis of cancer until proven otherwise. Consequently, physicians should be aware of the disorder and seek the cause when it is detected.

Acknowledgment

I wish to express my sincere appreciation to Dr. Seyed Habibollah Mousavi Bahar, for his valuable assistance in the treatment of the above patients and revision of this manuscript, without his favor this project would not have been possible