1. 4 Cancers That Spread Hematogenously
2. 4 Carcinomas That Spread Hematogenously

• Tumors that directly in vade the colon, or spread hematogenously, tend to involv e the outer layers of the bowel wall with relative sparing of the mucosa (Fig.
• Head and neck squamous cell carcinoma (SCCA) is well known for its local recurrence and spread via lymphatic and hematogenous routes. Areas of common metastasis from head and neck primaries include lung, liver, bone, kidney, adrenals, and the pleura. The brain is a rare site of metastasis for tumors originating in the head and neck.
• Lymphatic spread – colon carcinoma 2. Hematogenous spread – renal cell carcinoma. 2 Tumor Progression to. For many carcinomas, activation of RTK’s such as.

FA: Pathology-Carcinogens & Oncogenic Microbes study guide by JenBrockmeyer includes 26 questions covering vocabulary, terms and more. Quizlet flashcards, activities and games help you improve your grades. Usually are carcinomas rather than sarcomas.4. Lymphatic spread. 6 Thyroid carcinoma metastasizing to the jaw is extremely rare accounting about 3.85% of all jaws metastases & 0.1% of all malignancies. Hematogenously, affecting lung and bone most commonly. While distant metastases at.

Ali Solmaz¹, Ali Muhammedoğlu², Serdar Altınay², Candaş Erçetin¹, Erkan Yavuz¹, Osman Bilgin Gülçiçek¹, Şenay Yalçın², Yeşim Erbil³

¹Clinic of General Surgery, Bağcılar Training and Research Hospital, İstanbul, Turkey
²Clinic of Pathology, Bağcılar Training and Research Hospital, İstanbul, Turkey
³Department of General Surgery, İstanbul University İstanbul Faculty of Medicine, İstanbul, Turkey

Abstract

Metastatic neoplasms of the thyroid are uncommon when compared to primary tumors of the gland. Renal cell carcinoma (RCC) is a highly aggressive tumor of the urinary system. It can spread all over the body. Isolated solitary metastases of RCC to the thyroid are very rarely observed. A 64-year-old woman with a history of left radical nephrectomy for RCC, was referred to our clinic with palpable thyroid nodule. Ultrasound confirmed the nodule on the left lobe. Histopathological examination of the thyroidectomy specimen revealed that there were two solitary metastasis of RCC. No other distant metastasis were detected. Metastatic tumors of the thyroid gland are very rare. When patients with thyroid nodule are referred to our clinic with the history of other malignancies, we must consider metastasis. Thyroidectomy is recommended in the case of isolated thyroid metastasis of RCC.

Keywords: Renal cell carcinoma, metastasis, thyroidectomy

Introduction

Renal cell carcinomas (RCC), (also known as renal adenocarcinoma) are most common cancer type of kidneys originating from proximal tubules. It accounts for 2–3% of all adult malignancies and is also the seventh most common cancer in men and the ninth most common cancer in women (1). Renal cell carcinoma can metastasize to all organs hematogenously. In 30% of the cases, metastasis is present at diagnosis (2). The most common sites of metastasis are lungs, bone, lymph nodes, and liver (3). Gastric, brain, and skin involvement are also rarely seen. Although the thyroid gland is the second most common vascular organ of the body following the adrenal glands, metastasis of RCC is seen very rarely. In the autopsy series, tumors that metastasize to the thyroid are generally lung, breast, kidney, and head and neck (4). Isolated thyroid metastasis of RCC is very rare. When present, metastatic RCC mimics primary tumors of the thyroid gland. Renal cell carcinoma generally presents as a mass in the neck.

We describe herein a patient with solitary metastasis to the thyroid, who had undergone a left nephrectomy for RCC 17 months previously.

Case Presentation

A 64-year-old woman with a history of 15 years of non-toxic multinodular goitre was consulted to our clinic from urology. She had no other symptoms such as dysphagia or dyspnea. A physical examination revealed palpable nodules on both sites of the thyroid gland. She had a left nephrectomy operation 17 months earlier. She was followed-up without any other treatment. On follow-up, thoracoabdominal computed tomography (CT) showed enlargement of the thyroid gland and hypoechoic nodule with a diameter of 22 mm in the left lobe of the thyroid gland (Figure 1). Ultrasound was performed on this neck. There was heterogeneity of the gland and there was a 22 mm hypoechoic nodule in the left lobe. The result of the radiological features and the thyroid volume led us to operate the patient. She did not accept the fine needle aspiration cytology.

A total thyroidectomy was performed in our clinic. Parathyroid glands and recurrent nerves were recognized and preserved. Macroscopic examination of the specimen showed that there is a 2 cm and 0.5 cm nodule and an ill-defined 0.8 cm nodule on the left lobe. The right lobe was normal. Microscopic examination revealed that there is lymphocytic thyroiditis and nodular hyperplasia in the nodule that is 2 cm in diameter, but there are some atypical cells with clear cytoplasm and large vesicular nuclei and prominent nucleoli in the nodules (0.5 cm diameter). The same atypical cells were also found in an area of 0.8 cm in diameter, in the same lobe out of the nodules described. We learned from the history of the patient that she had left nephrectomy 16 months ago for pT3 RCC. Immunohistochemical examination showed strong immunoreactivity with RCC and CD10 and vimentin. These neoplastic cells were negative for thyroid transcription factor-1 (TTF-1). These findings proved that these two nodules, which are 0.8 and 0.5 in diameter, are the metastasis of RCC (Figure 2). After the operation, the patient was referred to the oncology clinic.

Discussion

Tumors of thyroid glands are mostly primary tumors, which are papillary, follicular, medullary, and anaplastic carcinomas in the order of frequency. On the other hand, metastatic thyroid gland tumors are seen very rarely and account for 2–3% of the thyroid malignancies (5). Common primary tumors metastasizing to the thyroid are lung, breast, kidney, and head and neck (4). These secondary thyroid gland tumors are found in 5–24% of the autopsy series. Metastases to thyroid in these autopsy series are generally multifocal, but in clinical series, metastases are solitary and <15 mm in size (6). Our patient displays similarities with literature in terms of the tumor diameter.

According to the article published by Chung et al. (7), the most common non-thyroid malignancies metastasizing to the thyroid are RCC (48.1%), colorectal (10.4%), lung (8.3%), breast carcinoma (7.8%), and sarcoma (4.0%). Metastases are generally nodular (44.2%) and are more common in females as observed in our case.

Renal cell carcinoma is the most common and very aggressive tumor of the urinary system. Its incidence increases with age. Until the widespread use of screening tests in recent years, many of the detected RCC had been metastasized. However, nowadays, by the use of these screening tests, 70% of them are detected as an incidental finding (8). This induces early detection of the cancer. However, despite early detection and surgical treatment, patients do not recover from the disease. We can see the metastasis of RCC even 10–20 years after diagnosis. Distant metastasis may be seen in one out of three patients. Our patient had left nephrectomy 16 months ago for pT3 RCC.

Renal cell carcinoma spreads hematogenously or through the lymphatic pathway to distant organs. The metastatic pathway is unpredictable for RCC. The lung, bone, liver, adrenal glands, brain, and skin are the most common sites of metastasis (8). The less frequent distant metastatic sites are orbit, parotid gland, nasal and paranasal cavities, tongue and tonsils, heart, skin, ovaries, uterus, testis, and thyroid glands.

The clinical findings of the primary and metastatic cancers of the thyroid gland are similar. We may not be able to differentiate them even with radiological evidences. Sometimes, fine needle aspiration biopsy may not be helpful in differentiating primary tumor from metastasis. However, if the pathologist is aware of the oncologic history of the patient, then by the use different antibodies and immunohistochemical studies, he/she may discriminate the pathology (9).

Thyroidectomy is recommended for isolated solitary thyroid metastasis of RCC. The mean survival rate after surgery is variable in the literature because the information about survival is limited to case reports. Heffess et al. (9) reported a series of 36 cases. According to this series, the mean overall survival period was 12.3 years from nephrectomy and 6.4 year from the date of thyroid metastasis. Machens and Dralle (10) reported that after definitive surgery of the thyroid metastasis of RCC, the mean survival rate may rise up to 30–60%. Considering that our patient, who was at an advanced age and presented with two nodules at a diameter of 5 mm and 8 mm, would have a poor prognosis, we are monitoring her closely in order to share her survival data in future studies.

Conclusion

Renal cell carcinoma can metastasize to distant organs even after many years. The thyroid gland is rarely affected by this. When the patient referred to our clinic with the thyroid nodule, we had data about the oncological history of the patient. If the patient had isolated thyroid metastases from RCC, thyroidectomy must be performed to improve prognosis.

Cite this paper as: Solmaz A, Muhammedoğlu A, Altınay S, Erçetin C, Yavuz E, Gülçiçek OB, Yalçın Ş, Erbil Y. Isolated thyroid metastasis from renal cell carcinoma. Turk J Surg 2017; 33(2): 110-112

Informed Consent

Written informed consent was obtained from patient who participated in this case.

Peer Review

Externally peer-reviewed.

Author Contributions

Concept - A.S., S.A.; Design - A.S., O.B.G., S.A.; Supervision - Y.E.; Funding - C.E., A.S.; Materials - A.M., S.A., Ş.Y.; Data Collection and/or Processing - E.Y., A.S.; Analysis and/or Interpretation - A.S., O.B.G., C.E.; Literature Review - E.Y., A.S.; Writer - A.S.; Critical Review - Y.E.; Other - A.S., O.B.G., S.A.

Conflict of Interest

No conflict of interest was declared by the authors.

Financial Disclosure

The authors declared that this study has received no financial support.

References

1. Rini B, Campbell S, Escudier B. Renal cell carcinoma. Lancet 2009; 373: 1119-1132.
2. De Stefano R, Carluccio R, Zanni E, Marchiori D, Cicchetti G, Bertaccini A, et al. Management of thyroid nodules as secondary involvement of renal cell carcinoma: case report and literature review. Anticancer Res 2009; 29: 473-476.
3. Hoffmann NE, Gillett MD, Cheville JC, Lohse CM, Leibovich BC, Blute ML. Differences in organ system of distant metastasis by renal cell carcinoma subtype. J Urol 2008; 179: 474-477.
4. Medas F, Calo PG, Lai ML, Tuveri M, Pisano G, Nicolosi A. Renal cell carcinoma metastasis to thyroid tumor: a case report and review of the literature. J Med Case Rep 2013; 7: 265.
5. Bohn OL, Casas LE, Leon ME. Tumor-to-tumor metastasis: renal cell carcinoma metastatic to papillary carcinoma of thyroid. Report of a case and review of the literature. Head Neck Pathol 2009; 3: 327-330.
6. De Lellis RA, Lloyd RV, Heitz PU, Eds CE. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Endocrine Organs. IARC Press, Lyon, France, 2004.
7. Chung AY, Tran TB, Brumund KT, Weisman RA, Bouvet M. Metastases to the thyroid: a review of the literature from the last decade. Thyroid 2012; 22: 258-268.
8. Koul H, Huh JS, Rove KO, Crompton L, Koul S, Meacham RB, et al. Molecular aspects of renal cell carcinoma: a review. Am J Cancer Res 2011; 1: 240-254.
9. Heffess CS, Wenig BM, Thompson LD. Metastatic renal cell carcinoma to the thyroid gland: a clinicopathologic study of 36 cases. Cancer 2002; 95: 1869-1878.
10. Machens A, Dralle H. Outcome after thyroid surgery for metastasis from renal cell cancer. Surgery 2010; 147: 65-71.

Abstract

Mandibular metastasis due to thyroid carcinoma is not very frequent and the cases described in the literature are few. Due to its bloodstream dissemination, most of them are a consequence of the follicular variant of thyroid carcinomas. We are presenting a case in which the metastatic lesion of mandible was detected before diagnosis of primary malignancy.

Introduction

Metastatic tumors of oral cavity are very rare, accounting for 1% of neoplasm in the area and their primary origin can be anywhere.[] Most such patients were previously diagnosed with primary neoplasm. The literature states that in about 30% of cases of patients with gnathic bone metastases, the primary tumor is asymptomatic and not diagnosed.[] The most common primary tumors leading to mandibular metastasis were lung in men and breast in women.[] These metastatic lesions (or tumors) usually are carcinomas rather than sarcomas.[]

Mandibular metastasis due to thyroid carcinoma is not very frequent and the cases described in the literature are few. Due to its bloodstream dissemination, most of them are a consequence of the follicular variants of thyroid carcinomas.[] We are presenting a case in which the metastatic lesion of mandible was detected before diagnosis of primary malignancy.

Case Report

A 40-year-old female patient reported to the oral medicine and radiology department with complaint of growth arising through nonhealing extraction socket since 3 months.

Three months back the patient developed diffuse extraoral swelling over lower left side of the face. After consultation with a local dentist, the patient underwent extraction of lower left first, second, and third molars. However, the swelling persisted even after extraction. Few days after extraction, the patient noticed a small growth arising from extraction socket. It was tender and used to bleed spontaneously. No history of paresthesia/numbness with the concerned region was reported.

The patient also revealed the presence of a small lump in the neck region, which she noticed 3–4 months prior; however, she neglected it as it was asymptomatic.

The patient was averagely built and had been cleaning her teeth with mishri (fine black powder of roasted tobacco leaves) since last 30–35 years.

General examination revealed the presence of lump in the midline of anterior region of neck; it was about 3.5 cm × 3 cm in size, soft to firm in consistency and was nontender. It used to move with swallowing.

Extraoral examination revealed swelling in the lower left side of the face. The swelling was oval shaped and was extending horizontally from mid-portion of left body of mandible to left angle of mandible and vertically from mid-ramus region to inferior border of mandible. It was tender, about 4.5 cm × 4.5 cm in size with bony hard consistency. The patient also presented with bilateral submandibular lymphadenopathy.

Intraoral examination revealed sessile growth [Figure 1] arising from extraction socket of lower left first, second, and third molars. It was about 3.5 cm × 2 cm × 2.5 cm in size with soft consistency and corrugated surface.

Intraoral photograph showing granulomatous growth arising from extraction socket

As the growth was arising from an extraction socket and the patient was a chronic tobacco chewer, a provisional diagnosis of malignant tumor of mandible was considered. The patient was then referred for radiographic examination, computed tomography (CT) scan imaging, complete blood count, and incisional biopsy of the intraoral growth.

OPG [Figure 2] revealed an osteolytic lesion in the lower left first, second, and third molars, which was ill defined, uncorticated. A pathologic fracture of the inferior border of the mandible was also noticed. Bone and soft tissue algorithm of CT scan [Figures ​[Figures33 and ​and4]4] examination revealed destructive lesion involving posterior region of body and ramus of the left mandible. On careful examination, soft tissue window revealed an expansile lesion with hyperintense periphery involving thyroid gland.

Orthopantomograph showing ill-defined osteolytic lesion with islands of remaining bone within the interior and pathologic fracture of lower border of mandible left side. (Digitally enhanced image)

Coronal section at bone window level showing osteolytic lesion causing erosion of lower border of left mandible

4 Cancers That Spread Hematogenously

Axial section at soft tissue window level showing destructive lesion involving posterior region of body and ramus of left mandible

Incisional biopsy of the intraoral growth revealed a metastatic follicular thyroid carcinoma.

The patient was then referred to higher center for further management.

Discussion

Follicular thyroid cancer tends to be a malignancy of older persons, with the mean age of patients in most studies being more than 50 years. Although papillary thyroid carcinomas are generally more common than follicular cancers, the latter are more prone to spread hematogenously, especially to lung and bones, with a rate of 5%–20%. Conversely, follicular cancers exhibit a relatively small propensity for lymphatic spread.[]

4 Carcinomas That Spread Hematogenously

Metastasis is a consequence of complex biologic cascade that begins with the detachment of tumor cell from primary tumor spreading into the tissues, invading the lymphovascular structures followed by their survival in the circulation.[] The microvasculature of the target organ provides room for the metastatic tumor cells to harbor, from where they can extravagate, proliferate, and invade within this target tissue. Angiogenesis is mandatory for the tumor cell load beyond 2–3 mm for adequate supply of oxygen and nutrients.[] Recent studies on the mechanism by which cancer metastasizes to bone have shown that cancer cells alter the physiologic balance between bone resorption and bone formation. Breast cancer metastases are frequently osteolytic and this has been attributed to overexpression of osteoclasts, inducing factors such as parathyroid hormone–related protein, interleukin (IL)-8, and IL-11.[] Predominantly osteoblastic metastasis is mediated by osteoblast-mediating factors, such as bone morphogenetic proteins, Wnt family ligands, endothelin 1, and platelet derived growth factors (PGDF). Furthermore, the release of matrix embedded growth factors, such as insulin-like growth factors and transforming growth factor-beta upon osteolysis promotes the induction of osteoclast-promoting factors.[]

Reports from different parts of the world show a variable incidence of metastasis to jaw bone from different primary sites, ranging from 1–4 cases per year.[,] Most of the metastatic tumors occur in 5^th, 6^th, and 7^th decades[,]; however, in an Indian study the metastatic tumors were found to occur at an early age between the 3^rd and 7^th decade. In the younger age group (first to second decade) the metastasis was found to occur from adrenal neuroblastoma, medulloblastoma, and osteogenic sarcoma.[] The clinical presentations of the metastatic lesions include pain, swelling, loosening of tooth, paresthesia, and pathologic fracture.[,] Less frequently the lesion can present as pain in the temporomandibular joint region or as an osteomyelitis in the jaw or as trigeminal neuralgia.[] Studies have shown that chronic trauma to the oral tissue favors metastatic spread to the oral cavity.[14] In another study it was found that in 55 cases tooth extraction preceded the discovery of metastasis.[] In the majority of the cases, a latency period of 2 months between the extraction and the development of the metastasis was reported. In our case also we observed a similar finding. Thus the role of trauma to the oral mucosa in the causation of oral metastasis needs further investigation.

Emre and Ehab studied various cases and observed that the most frequent location for metastasis among jaw bones is mandible. In the mandible, ramus and angle are more commonly involved. They concluded that the propensity of posterior mandible for metastasis is due to its better vascularity.[] A few investigators believe that metastasis to jaw bone through hematogenous route requires the presence of hematopoietically active bone marrow well connected with the sinusoidal vascular spaces at the site of deposition of malignant cells.[,]

The posterior mandible and the focal osteoporotic bone marrow defects in the edentulous mandible have been shown to be the hematopoietically active sites that may attract the metastatic tumor cells.[,] Still some other investigators believe that the high bone turnover in this region may be the cause.[]

Although the incidence of metastatic tumors in oral cavity is considered low, a significant number of such lesions have a high tendency to go undetected, this is because of the following:

1. Micrometastasis is rarely detected by radiographic survey.[]

2. Cases with poor prognosis and terminal stage of the disease lose or are dead before presenting to a clinician.[]

3. Earlier jaw bones were not included in the radiographic survey for metastatic workup.[]

The exact incidence of metastatic diseases that affect the mandible is still unknown. Hence all medical and dental clinicians must include malignant disease, primary or metastatic, alongside the more common benign pathologies when considering the differential diagnosis of oral complaints. This is particularly important in the primary care setting, especially when dealing with elderly patients, or those with a history of malignancy.

Footnotes

Source of Support: Nil.

Conflict of Interest: None declared.

References