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 Table of Contents  
REVIEW ARTICLE
Year : 2018  |  Volume : 15  |  Issue : 2  |  Page : 60-64

Collision tumors of the thyroid: Review of literature and report of a case of papillary–Follicular collision tumor


Department of General and Laparoscopic Surgery, M.O.S.C. Medical College, Kolenchery, Kerala, India

Date of Web Publication17-Jul-2018

Correspondence Address:
Vijy Paul Thomas
Department of General and Laparoscopic Surgery, M.O.S.C. Medical College, Kolenchery - 682 311, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/trp.trp_6_18

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  Abstract 


It is a known fact that thyroid malignancies are the most common of endocrine malignancies. Furthermore, differentiated thyroid malignancies including the papillary and follicular types are the most common among these malignancies of the thyroid. However, it is extremely uncommon to get a combination of two primary malignancies within the same thyroid gland. These combinations can be classified into collision tumors, mixed tumors, and composite tumors. Whenever such tumors have been described, they have almost always been combinations of papillary carcinoma and medullary carcinoma. Recently, a couple of cases of combinations of papillary and follicular carcinomas are being reported. It is difficult to completely explain the occurrence of such tumor types together in the same gland. Various theories have been proposed to explain this simultaneous occurrence such as the stem cell theory, collision theory, and the hostage theory. It is now accepted that these tumors should be considered more aggressive and having a higher risk of recurrence as compared to either of the tumors occurring independently. Treatment should be patient specific and is directed by the more aggressive of the tumors; however, no standardized protocols for diagnosis or treatment have evolved due to lack of significant information on their behavior.

Keywords: Carcinoma, collision tumors, follicular, medullary, papillary


How to cite this article:
Thomas VP, George R. Collision tumors of the thyroid: Review of literature and report of a case of papillary–Follicular collision tumor. Thyroid Res Pract 2018;15:60-4

How to cite this URL:
Thomas VP, George R. Collision tumors of the thyroid: Review of literature and report of a case of papillary–Follicular collision tumor. Thyroid Res Pract [serial online] 2018 [cited 2018 Oct 20];15:60-4. Available from: http://www.thetrp.net/text.asp?2018/15/2/60/236706




  Introduction Top


Collision tumors, which are histologically distinct malignant tumors coexisting in the same organ, although rare in occurrence, have been described in many sites. Some of the organs implicated are the liver, stomach, adrenal gland, ovary, lungs, kidneys, and colon. Even more rarely, these tumors may be found in the thyroid gland. Here too, it is the combination of papillary carcinoma with medullary carcinoma that is seen to occur. Here, we present the report of a case of follicular carcinoma–papillary carcinoma combination of the thyroid.


  Case Report Top


A 33-year-old male presented with an anterior neck swelling of 6-month duration with no other associated symptoms. On examination, he was found to have a solitary nodule of the right lobe of thyroid with deviation of the trachea to the left and no palpable enlarged lymph nodes. Thyroid function tests were normal. Ultrasound scan of the neck showed a 3.6 cm × 3.0 cm hyperechoic nodule in the right lobe of thyroid with multiple internal cystic areas. Fine-needle aspiration cytology was done and reported as adenomatous nodule/follicular neoplasm. Hence, a right hemithyroidectomy was done. Postoperative period of hospital stay was uneventful. Histopathologic examination of the resected specimen showed it to be 8 cm × 6 cm × 2.5 cm with two nodules – one 4 cm × 4 cm × 6 cm and a smaller one 0.8 cm. Within the larger nodule was a neoplasm composed of closely packed follicles showing capsular invasion at two sites but no vascular invasion [Figure 1]. Thyroid tissue outside the neoplasm showed lymphocytic thyroiditis. The second nodule showed a focus of papillary microcarcinoma [Figure 2]. Biopsy was reported as minimally invasive follicular carcinoma with capsular invasion, a focus of papillary microcarcinoma in the second nodule, and thyroid tissue outside the neoplasm showing lymphocytic thyroiditis. Consequently, completion thyroidectomy was done and again postoperative period was uneventful. Histopathologic examination of this specimen revealed Hashimoto's thyroiditis. Radioactive iodine scan done 3 months later showed one focus of increased uptake in the region of the thyroid bed and no distant metastasis. Radioactive iodine ablation was done with 2923 MBq of I-131. He was later started on suppressive doses of L-thyroxine. He is presently asymptomatic and is carrying on with his earlier occupation without any restrictions and latest thyroid-stimulating hormone (TSH) value is 0.02 μIU/mL (0.465–4.68).
Figure 1: Follicular carcinoma in the lesion showing capsular invasion

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Figure 2: Papillary microcarcinoma within the lesion

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  Discussion Top


Thyroid malignancy is the most common type of endocrine cancer and its incidence has been continuously increasing worldwide. Different types of thyroid cancer have been described including differentiated thyroid cancers – papillary and follicular, medullary, undifferentiated or anaplastic, lymphoma, and metastasis. Of these, the anaplastic variety and metastases generally carry a poor prognosis. Although differentiated thyroid malignancies of the thyroid are common, it is rare for the gland to harbor more than one type of malignancy at the same time. This kind of dual pathology affecting the thyroid gland could take different forms such as medullary carcinoma–papillary carcinoma combination or squamous cell carcinoma–papillary carcinoma combination.

Multiple primary tumors occurring together, to be considered so, need to satisfy the criteria established first by Bilroth and later modified by Warren and Gates. These are (i) each tumor must demonstrate a definite picture of malignancy, (ii) each tumor must be distinct, and (iii) the possibility that one of the tumors is a metastatic lesion from the other should be excluded. Such combinations of tumors occurring in the same gland or organ could be one of three types – collision tumors, mixed tumors, or composite tumors.

A collision tumor is described as the coexistence of two adjacent but histologically distinct and morphologically independent malignant tumors in the same organ with no histological admixture. In contrast, the term mixed tumor is used when there is a histological admixture of the two tumors in the same organ.[1],[2] Mixed tumors are, therefore, thought to have a common cell of origin.[3] The term composite tumor, in turn, refers to the condition where a tumor contains two discrete cell populations as with thyroglobulin positive papillary carcinoma cells and calcitonin-positive medullary carcinoma cells.[3] Collision tumors can occur in various organs such as the ovaries, colon, lung, stomach, skin, and kidneys but are extremely rare in the thyroid.[4] The most common type described is the presence of mixed histology consisting of papillary and medullary carcinomas.

Some pairs of collision tumors have been noted to occur with slightly increased frequency, for example, hepatocellular carcinoma and cholangiocarcinoma and gastric adenocarcinoma and gastric lymphoma.[5],[6] Of such combinations of tumors in the thyroid, the various types described include the more common papillary carcinoma – medullary carcinoma collision tumors and extremely rarely even metastatic liposarcoma from the thigh to the thyroid with a focus of papillary carcinoma.[7] Interestingly, cases of synchronous follicular carcinoma, papillary carcinoma, and medullary carcinoma in the same thyroid gland have also been described, although very rarely. The first case of synchronous papillary and follicular carcinoma of the thyroid with metastasis to lymph node and bone, respectively, was reported in the year 2018.[8]

Differentiated thyroid cancers including both papillary and follicular carcinomas which originate from the thyroglobulin-secreting follicular cells are the most common type of thyroid malignancy, constituting about 80%, whereas medullary carcinoma which originates from the calcitonin-producing parafollicular C cells is relatively rare at about 5%–10%. Although collision tumors of the papillary-medullary type are the common type described, even this presence of concurrent papillary and medullary pathological features in a single thyroid tumor is extremely rare, constituting about 1% of all thyroid malignancies. They are actually two distinct types of thyroid malignancies with considerable difference in terms of cellular origin, histopathologic appearance, clinical course, and prevalence.[9] There are no pathogenetic mechanisms available so far to completely explain neoplastic transformation of follicular cells and parafollicular C cells within the same thyroid nodule.[10]

The most widely accepted hypotheses suggested to explain the concurrent occurrence of medullary carcinoma and papillary carcinoma thyroid are stem cell theory, random collision effect theory, and hostage theory.[7] The stem cell theory postulates that such tumors are the result of the ability of cancer stem cells to differentiate into different tumor cell lines in the same organ or anatomic site.[11] It is thus possible that two entirely different tumors could arise very close to each other from adjacent cancer stem cell lines. This is supported by the occurrence of coexpression of thyroglobulin, synaptophysin, and chromogranin by the papillary component of collision tumors. However, this theory cannot describe collision tumors involving cell types of distinct embryologic origin occurring in the thyroid. The random collision effect theory suggests the possibility that two separate and distinct tumor types, either a medullary carcinoma thyroid and a follicular carcinoma or a medullary carcinoma thyroid and a papillary carcinoma thyroid, get initiated in close proximity to one another, thus resulting in a polyclonal neoplasm which, however, gets clinically recognized as a single tumor. Positive staining for calcitonin but not for thyroglobulin in the medullary component of the tumor along with the separation of tumors by an area of normal thyroid tissue have been highlighted by proponents of this theory as indicating the likelihood of a collision effect.[6] These tumors are actually polyclonal and show different genetic alterations in each component of the tumor. Field cancerization, a concept suggested first by Slaughter et al. in 1953, is important here. It was proposed that the multicentric origin and the high probability of cancer recurrence in the oral mucosa were due to the presence of a genetically altered field of precancerous cells. This field cancerization generates multifocal areas of cancer development from multiple genetically distinct clones precipitated by carcinogenic events. Each of these cancer clones is thought to originate from a different cancer stem cell and bear different genetic alterations. These cancer clones can thus lead to tumor development either synchronously or metachronously.[12] The hostage theory, also described as neoplastic coercion, is based on a situation in which normal thyroid follicles get entrapped within a focus of medullary carcinoma and later undergo hyperplasia and finally neoplastic transformation.[13] This theory is also corroborated by the fact that some medullary carcinomas may exhibit entrapped and well-preserved thyroid follicles exhibiting cytological features unlike that of the surrounding nonneoplastic follicles. Some unknown trophic factors secreted by the tumor may be responsible for keeping the entrapped follicles alive or even stimulate them to proliferate. Furthermore, it is possible that some follicles may secrete substances that prevent them from being destroyed by the medullary carcinoma within which they are entrapped. This microenvironment within the medullary carcinoma could be responsible for the formation of adenomatous follicular foci which could later on become neoplastic foci through the acquisition of molecular defects.[14] In addition, it is worthy to note that medullary carcinoma thyroid, unlike most other human cancers, exhibits a different pattern of growth which does not destroy the tissue in which it arises. However, this theory cannot explain why such tumors are then so rare. Furthermore, it is unable to define the conditions that need to exist in the first primary tumor to promote the growth of a second tumor. Most of the literature describes the co-occurrence of medullary carcinoma thyroid and papillary carcinoma thyroid or metastatic tumors along with papillary carcinoma thyroid. The first report of a collision tumor of follicular carcinoma thyroid and papillary carcinoma thyroid was made by Plauche et al. in the year 2013.[15] Follicular and papillary carcinomas of the thyroid are both types of differentiated thyroid carcinoma and generally are tumors with a relatively good prognosis. However, the presence of two primary cancers, even though of the differentiated type, should be considered as signifying an aggressive potential and also an increased risk of recurrence.[15]

The tumorgenesis of various types of thyroid carcinoma has been studied and several genes and genetic alterations involved have been identified. BRAF mutations were exclusively detected in papillary carcinoma thyroid in 30%–70% cases.[16] Furthermore, somatic rearrangements of RET/PTC were also noted to be highly prevalent in papillary thyroid carcinoma.[17] A model for thyroid carcinogenesis called the “fetal cell carcinogenesis” model was proposed by Takano in 2004.[18] In contrast to the conventional multistep carcinogenesis model where thyroid carcinomas are thought to develop from thyrocytes through multiple genomic changes, the fetal cell carcinogenesis model suggests that thyroid carcinomas originate from remnants of fetal thyroid cells that have the ability to migrate to surrounding tissues. This model believes that papillary carcinomas, follicular tumors, and anaplastic carcinomas are derived from the remnants of thyroblasts, prothyrocytes, and thyroid stem cells, respectively.[18] Moreover, since follicular cells are the end result of the process of differentiation, follicular tumors can originate from several different cells including thyroid stem cells, thyroblasts, and prothyrocytes, whereas papillary carcinoma almost always are derived from thyroblasts. As per this theory of fetal cell carcinogenesis, follicular carcinoma can hence arise from a papillary carcinoma which originates first or both tumors could originate from a common stem cell.

There is also a view contrary to the one described above. Follicular carcinoma of the thyroid including its Hurthle cell/oncocytic variants, unlike papillary carcinoma, has not been shown to have any great association with BRAF or RET oncogene rearrangements.[19] Furthermore, increased incidence of follicular carcinoma thyroid in populations in iodine deficiency areas has been shown to correlate well with chronic elevation of TSH.[20] Hence, as per this view, it is but natural that synchronicity should be coincidental rather than due to a genetic linkage. In addition, it is pertinent to note that only 25% of medullary carcinoma thyroid cases are linked to RET oncogene activation, while the vast majority (75%) are sporadic. This again is suggestive of a nongenetically linked pathogenesis in the vast majority of cases. To explain the combination of papillary carcinoma and squamous cell carcinoma thyroid, what has been suggested is either an embryologic origin as could happen with the presence of a branchial cyst or a persistent thyroglossal duct, or as a result of chronic inflammation or the primary thyroid malignancy itself promoting squamous metaplasia.[21] As of now due to inadequate data and evidence, a single theory cannot explain the pathogenesis of all of such collision tumors and hence a combination of theories will have to be accepted.

Management plan of collision tumors of the thyroid is usually complex due to the presence of dual pathology in the tumor tissues and also the fact that literature on this condition is pretty scarce. Generally, the treatment needs to be patient specific and what is suggested is that treatment should be guided by the more aggressive of the neoplasms.[22] It has also been suggested that each component of the combination should be treated like an independent primary.[22],[23] Surgical management with adjunct therapy is the recommendation.[22]


  Conclusion Top


Collision tumors are a rarity but are now being increasingly reported from across the globe. They are a diagnostic as well as therapeutic challenge due to the dual pathology that they harbor. No single theory can completely explain the pathogenesis of these tumors in all cases, and so, with the present level of understanding of the disease, a combination of theories has to be accepted. Specific treatment guidelines are almost not available due to the absence of much of literature on this topic as well as the fact that the reports that are available do not have much of data on long-term follow up of such patients. It is hoped that with greater reporting and follow-up of these and other such patients, standardized diagnostic and treatment protocols will be evolved.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Nikiforov YE, Biddinger PW, Lester DR. Diagnostic Pathology and Molecular Genetics of the Thyroid: A Comprehensive Guide for Practicing Thyroid Pathology. Washington DC: Lippincott Williams and Wilkins; 2012.  Back to cited text no. 13
    
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Volante M, Papotti M, Roth J, Saremaslani P, Speel EJ, Lloyd RV, et al. Mixed medullary-follicular thyroid carcinoma. Molecular evidence for a dual origin of tumor components. Am J Pathol 1999;155:1499-509.  Back to cited text no. 14
    
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Plauche V, Dewenter T, Walvekar RR. Follicular and papillary carcinoma: A thyroid collision tumor. Indian J Otolaryngol Head Neck Surg 2013;65:182-4.  Back to cited text no. 15
    
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Fukushima T, Suzuki S, Mashiko M, Ohtake T, Endo Y, Takebayashi K, et al. BRAF mutations in papillary carcinomas of the thyroid. Oncogene 2003;25:6455-7.  Back to cited text no. 16
    
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