Collision tumors of thyroid

1. Collision tumours of thyroid
Clinicopathological and
Molecular Profiling of a rare entity

2. INTRODUCTION
 Collision tumors at any site are defined as histologically
distinct and morphologically independent malignant
tumors that coexist geographically.1
 Collision Tumor of thyroid represents the presence of
two intimately associated but morphologically different
malignant neoplasms in the thyroid.2
 Although differentiated thyroid malignancies of the
thyroid with multi-focality is no longer considered a rare
event, it is extremely uncommon for the gland to harbor
more than one type of malignancy at the same time.3

3.  This kind of dual pathology affecting the thyroid gland
could take different forms such as medullary carcinoma–
papillary carcinoma combination , squamous cell
carcinoma–papillary carcinoma combination etc. 1,2
 We undertook an extensive literature search of the PubMed
data bases from 1985 till date and identified only 36 cases
of collision tumors in 30 different publications.
 All these were case reports and to the best of our
knowledge, this is the first documentation of a case series
of collision tumor of the thyroid gland and the first ever
attempt for molecular profiling.

4. REVIEW OF LITERATURE
 The first report of Collision tumors of the thyroid was
found to be in 1985 by Ishida et al in Japan.5
 Since then, several hypotheses have been suggested as
mechanisms for origin of collision tumors.
 Most of the studies showed a predominance for women
with average age range of 53 years. 5
 The most common collision tumor was that of papillary and
medullary carcinomas with metastatic deposits common at
the time of presentation.5

5.  Genetic alterations form the basis of thyroid carcinogenesis.
 Most alterations occur in genes for important signaling
pathways, in particular the mitogen-activated protein
kinase (MAPK) pathway, the study of which can have
potential use as diagnostic, therapeutic and prognostic
targets.
 A multidisciplinary therapy was adopted with surgery and
adjuvant treatment in majority of the case reports.
 Until date, even though multiple case reports were published
all over the world, only four case reports are from India and
one from Kerala.

6. RESEARCH QUESTION
What are the clinico-pathological, molecular characteristics
and prognostic features of patients diagnosed with collision
tumors of thyroid at Malabar Cancer Centre, Thalassery
during the period Jan 2012- Dec 2019?

7. AIM AND OBJECTIVE
AIM:
 To study clinico-pathological molecular and
prognostic/survival features of patients diagnosed with
collision tumors of thyroid
PRIMARY OBJECTIVE
 To study the clinico-pathological and molecular features of
collision tumors of thyroid
 To study the prognostic /survival features of collision
tumors of thyroid

8. MATERIALS AND METHODS
 Study setting - Division of Oncopathology, Division of
Molecular Oncology, Department of CLSTR, MCC,
Thalassery
 Study design –Prospective
 Study period –4months, August- November 2020
 Expected Sample size – 5 to 10
 Study population – All cases of collision tumor of thyroid
diagnosed during the period from Jan 2012 – Dec 2019

9. METHOD OF DATA COLLECTION:
 Clinical details including demographic details will be
obtained from the patient’s record file retrieved from the
Department of Cancer Registry of the hospital.
 The pathological details will be retrieved from archives of
division of Oncopathology.
 Treatment offered, response to treatment and clinical
outcome will be recorded from case files for all the
patients.
 The status of molecular markers will be detected from
FFPE blocks archived in the division of Oncopathology

10. Genomic studies
The status of KRAS mutation and BRAF mutation in the
archived biopsy samples will be evaluated using Sanger
sequencing or through ARMS PCR
Proteomic studies
We aim to develop an in-house novel untargeted shot-gun
proteomic method for the detection of molecular markers
from FFPE samples
METHOD OF DATA COLLECTION:

11. GENOMIC STUDIES WORK FLOW
DNA Extraction from FFPE samples using commercial
FFPE DNA extraction kit
Quality evaluation of the extracted DNA
Mutation analysis
through Sanger
sequencing
BRAF/KRAS Mutation
analysis through
Amplification
Refractory Mutation
System (ARMS) PCR

12. PROTEOMIC STUDIES WORK FLOW
Extraction of total protein from FFPE samples
Protein estimation using BCA assay followed by
quality evaluation on SDS PAGE
Tryptic digestion of the normalized proteins
LC/MS/MS analysis using Thermo Q Exactive coupled
with nano LC system
Data analysis using Proteome discoverer 2.2

13. ETHICAL CONSIDERATIONS
 The permission from the institutional review board/
Institutional scientific committee will be obtained for the
study.
 The process of data collection will not pose any risk or
harm to the subjects as no kind of intervention or any
interference with treatment is undertaken in this study.
 Waiver of informed consent from IEC will be applied to
perform genomic and proteomic studies
 Data confidentiality: The names of the patients will not be
entered anywhere in the study.

14. DISSEMINATION OF RESULTS
 The results will be published in peer reviewed national
/international journals and conferences, increasing the body
of knowledge and informing the larger scientific/medical
body.

15. REFERENCES
1. 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.
2. Warman M, Lipschitz N, Ikher S, Halperin D. Collision tumor of the
thyroid gland: primary squamous cell and papillary thyroid carcinoma.
ISRN otolaryngology. 2011 May 31;2011.
3. Baloch ZW, Mandel S, LiVolsi VA. Combined tall cell carcinoma and
Hürthle cell carcinoma (collision tumor) of the thyroid. Archives of
pathology & laboratory medicine. 2001 Apr;125(4):541-3.
4. Walvekar RR, Kane SV, D'Cruz AK. Collision tumor of the thyroid:
follicular variant of papillary carcinoma and squamous carcinoma.
World journal of surgical oncology. 2006 Dec 1;4(1):65.
5. Ryan N, Walkden G, Lazic D, Tierney P. Collision tumors of the
thyroid: A case report and review of the literature. Head & neck. 2015
Oct;37(10):E125-9.

16. PROFORMA:
Name: Age/Sex: UHID: Biopsy No:
•Previous H/o radiation:
•Occupation :
•Family history:
•Clinical presenting symptoms:
•Duration of complaints (months):
Investigations:
•USG- TIRADS 1st case TIRADS 2nd case
•Cytology- FNAC 1st case FNAC 2nd case
•Clinical staging : (cT, cN)
Histological details:
•LN involvement
•ENE
•Prognostic stage (AJCC, 8th ed):

17. Histologic type:
Tumor size:
Tumor site:
Predominant pattern:
LVE
PNI
ETE
Pathological stage:
(pT N)
BRAF Mutation
KRAS Mutation
RAS Mutation
TUMOR 1 TUMOR 2

18. Treatment details:
•Started On: Completed on:
•Surgery:
•Adjuvant treatment received: yes/ no
•Radioiodine treatment:
•Recurrence: yes/no Date of recurrence: Date of last follow up:
•Status: Alive/Dead
•DFS:
•Overall Survival: