Abstract
Collision tumor comprise of existence of two histologically distinct and separate neoplasms in any organ. Thyroid gland is an uncommon site for these tumors, with frequently involved organs being liver, adrenal and stomach. Even among the synchronous tumors of thyroid, papillary and medullary carcinoma are most commonly reported. The present case reports a rare presentation of a collision tumor comprising of papillary and follicular carcinoma with scalp metastasis from the follicular carcinoma and lymph nodal metastasis from the papillary component.
It is essential for the clinician to be aware of such an entity so as to guide further treatment and management.
Keywords: Collision tumor, Follicular carcinoma, Papillary carcinoma, Synchronous tumor, Thyroid
Introduction
Collision tumors is characterized as the existence of two or more histologically and geographically separate neoplasms in any organ. The most frequently involved organs with these tumors include liver, adrenal, stomach, ovary, lungs, colon and kidney [1].
Collision tumors are very rarely seen in the thyroid gland with most of them comprising of papillary and medullary tumors [2–5].
Papillary and follicular carcinomas arise from the thyroid follicular cells. Despite these tumors being the most common tumors of thyroid, collision tumor comprising of these components are rarely reported [6, 7].
We report a rare case of collision tumor comprising of papillary (PTC) and follicular carcinoma (FTC) with scalp metastasis from the follicular carcinoma and lymph nodal metastasis from the papillary component.
Case Presentation
A 35-year female patient presented with complaints of right sided scalp swelling for one month. The swelling was insidious in onset and gradually progressive and associated with heaviness in the ear and headache. She also gave history of swelling in the anterior neck for last three months which was increasing in size. There was no significant family or personal history. There were no complaints of altered bowel habits, irregular menstrual cycles and any heat/ cold intolerance.
On examination, the scalp swelling was 6 × 4 cm, soft to firm, cystic in consistency with a regular border and smooth surface. There was an anterior neck swelling measuring 5 × 4 cm which was firm to hard in consistency and moved with deglutition. The trachea was deviated to the left side and there were multiple small cervical lymph nodes palpable in Level II, III and IV. There was no lid lag, exophthalmos or any other eye signs. Her thyroid profile was within normal limits.
Ultrasound neck revealed a well-defined multilobulated, solid cystic mass lesion noted in right lobe and isthmus with increased vascularity on colour Doppler. Multiple subcentimetric lymph nodes were also seen in the bilateral cervical region largest measuring 12.4 × 4.4 mm on right side. Computed tomography of neck showed a large solid nodule in right lobe of thyroid gland and isthmus with a dense calcific focus within and retrosternal extension. Also seen is a 33 × 45 mm lytic lesion in the left temporal bone with breach of inner and outer cortex and associated extraosseous soft tissue component with intracranial extradural soft tissue component causing indentation on the left temporal lobe. A possibility of metastasis was suggested on radiological workup.
Fine needle aspiration cytology was done from both the scalp and the thyroid swelling. The smears from the anterior neck swelling were cellular with follicular cells arranged as sheets, microfollicles, macrofollicles, papillaroid fragments with presence of nuclear overlapping. Nuclear grooving was also observed in some of the cells. It was reported as Suspicious for papillary carcinoma- Bethesda category V.
Smears from the scalp swelling were cellular and exhibited cells arranged in macrofollicular and microfollicular pattern. There was minimal nuclear atypia with round to oval nucleus and moderate cytoplasm. No papillary fragment or any nuclear features were observed. Based on the cytopathological and radiological findings, a possibility of metastasis from thyroid carcinoma / malignant adnexal tumor was suggested. [Figure 1]
Fig. 1.
Clinico-radiological and cytological findings of the scalp and neck mass. Clinical image of the scalp swelling which had regular borders with smooth surface Computed tomography scan showed lytic lesion in the left temporal bone with breach of inner and outer cortex. c-d) Fine needle aspiration cytology of scalp mass showed repetitive microfollicles with mild pleomorphism in a background of scant colloid. [May Grunwald Giemsa, Papanicolaou stain, x40, x10 magnification]. e) Clinical image of the anterior neck swelling which was involving almost entire thyroid gland. f) Computed tomography scan of neck showed large solid nodule in right lobe of thyroid gland and isthmus with retrosternal extension. g-h) Fine needle aspiration cytology of neck mass showed papillaroid fragments with moderate pleomorphism, nuclear enlargement and overlapping, grooving and intranuclear inclusions. [May Grunwald Giemsa, x40 magnification]
The patient was taken up for total thyroidectomy and central lymph node dissection and specimen was sent for histopathological examination. The thyroid gland was enlarged and multilobated. Cut surface showed a solid greyish white mass with a nodular pattern involving the entire thyroid gland including the right lobe, isthmus and left lobe and measuring 6.7 × 4.5 × 3.5 cm. Focal areas of hemorrhage and calcification were also observed.
Histopathological examination revealed two morphologically distinct malignant tumors. The first tumor which involved almost the entire thyroid gland was arranged in repetitive microfollicular pattern. The cells were monomorphic with presence of focal capsular and vascular invasion. This tumor did not show the presence of any nuclear features or papillary architecture. One of the nodules (measuring 1.5 × 1 × 1 cm) near the inferior pole of left lobe demonstrated completely different morphology- the tumor cells were arranged as papillae with fibrovascular cores. The cells exhibited nuclear overlapping, clearing with presence of intranuclear inclusions and grooving. The follicular carcinoma exhibited extrathyroidal extension. Four out of the 10 lymph nodes examined showed metastatic papillary carcinoma. [Figure 2] Thus, a final diagnosis of synchronous follicular pT4 N0 and papillary carcinoma with nodal metastasis, pT2 N1 was made.
Fig. 2.
Gross and histopathological images of the neck mass. a) The thyroid gland was enlarged and multilobated with a solid greyish-white mass with a nodular pattern involving the entire thyroid gland including the right lobe, isthmus and left lobe. (Blue arrow indicates the papillary thyroid carcinoma). b-d) Low power photomicrographs from follicular carcinoma showing microfollicles with capsular (c) and vascular (d) invasion. [Hematoxylin and eosin stain, x10 magnification]. e) High power photomicrographs from follicular carcinoma depicting thyroid follicular cells arranged as microfollicles with mild nuclear pleomorphism. [Hematoxylin and eosin stain, x40 magnification]. f-g) Papillary Carcinoma focus - Tumor cells arranged in papillae with nuclear clearing and grooving . [Hematoxylin and eosin stain, x10, x40 magnification]. h) Lymph node exhibiting metastatic papillary carcinoma. [Hematoxylin and eosin stain, x10 magnification]
The patient was given radioactive iodine following surgery and currently patient is on follow-up with no evidence of recurrence.
Discussion
Papillary carcinoma is the most common malignancy of thyroid followed by follicular carcinoma. However, synchronous malignancies are rarely reported in thyroid gland.
The most common synchronous thyroid malignancies reported include medullary carcinoma with papillary carcinoma. Till date very few cases of synchronous follicular [FTC]- papillary [PTC] carcinoma have been reported, with two of them also showing an additional medullary carcinoma. 6–15.
Table 1 depicts the summary of radiological and pathological parameters of the different cases of concurrent FTC and PTC reported till date.
Table 1.
Summary of previously reported cases of synchronous follicular and papillary carcinoma
| Author | Age/ Sex | Radiological findings | Cytological findings | Follicular carcinoma | Papillary carcinoma | Perineural invasion | Lymphatic/ Angioinvasion | Follow-up | |
|---|---|---|---|---|---|---|---|---|---|
| Abdelaal et al.7 (2020) | 31/F | USG- A large left-lobe thyroid nodule with small thin peripheral halo, peripheral and central vascularity and coarse calcifications. | Follicular cells of undetermined significance (FLUS). | pT3N0, left lobe (5 × 4 cm) | pT1bN0, left lobe (1.3 cm) | Absent | Absent | No residual/recurrence | |
| 61/M | USG- Enlarged right thyroid lobe with a large isoechoic, heterogenous nodule occupying entire lobe, with slightly increased peripheral vascularity. | Suspicious for follicular neoplasm | pT3aNx, right lobe (6 × 3 cm) | pT1aNx, right lobe (0.3 cm) | Absent | Present (angioinvasion) | No evidence of residual disease | ||
| 59/M | USG- left lobe and isthmus were enlarged with multiple nodules, showing solid complex echotexture with partially ill-defined margins | Follicular lesion of undetermined significance (FLUS) on a background of lymphocytic thyroiditis | pT3aNx, left lobe (5 cm) | pT1bNx, left lobe (1.5 cm) | Absent | Present (lymphatic invasion) | No evidence of residual disease | ||
| 56/M | USG- Two hypoechoic nodules in the right lobe, the largest was ill-defined with coarse calcification. | Atypical follicular lesion of undetermined significance (AUS) | pT3aNx, left lobe (4.5 × 3.5 cm) | pT1aNx, both lobe (0.6 cm) | Absent | Present (lymphatic invasion) | Lost to follow-up | ||
| 35/M | USG- Heterogeneous echopattern with mild increased vascularity and multiple nodules with calcification in both lobes | Malignant cells consistent with Papillary Thyroid Carcinoma | pT1bN0, right lobe (1.3 cm) | pT1aN0, right lobe (0.8 cm) | Absent | Absent | Lost to follow-up | ||
| 52/M | USG- Multiple right lobe solid thyroid nodules, with isoechoic nodule in left lobe | FLUS | pT2Nx, right lobe (2.7 × 1.5 cm) | pT1aNx, right lobe (0.8 × 0.6 cm) | Absent | Absent | No evidence of residual disease | ||
| Cracolici et al.6 (2018) | 63/F | - | - | Right lobe, 1.1 cm | Left lobe, 1.7 cm | Absent | Absent | Alive with disease | |
| Awadalla et al.8 (2022) | 59/F | USG-complex left thyroid nodule- 4.7 cm in greatest dimension and right thyroid nodule around 1.9 cm, both associated with micro-calcifications |
Left lobe- AUS, Right lobe- Benign follicular nodule |
Left lobe, 4.7 cm |
Papillary microcarcinoma, Left lobe | Absent | Present | No evidence of recurrence | |
| Feng et al.9 (2020) | 40/F | USG- Thyroid nodule | - | Left lobe | Right lobe, 1.8 × 1.2 cm | Absent | - | No evidence of disease | |
| Plauche et al.10 (2013) | 62/F | USG- diffusely nodular thyroid gland, with a 5.7 cm × 3.0 cm predominantly solid nodule in the left thyroid lobe. |
suspicious for follicular neoplasm |
Left lobe, 4.1 cm | Left lobe, 1 cm | Absent | Present | - | |
| Cupisti et al.11 (2005) | 52/M | UGS- Right lobe showed multiple echo-homogeneous and echo- complex nodules. Left lobe had echo complex and cystic nodules. | - | Right lobe, 5 cm |
Right lobe, 0.3 cm (Papillary microcarcinoma) Left lobe- Medullary carcinoma, 1.5 cm |
Absent | Present | - | |
| Ganguly et al.12 (2010) | 64/F | - | Degenerated cells in a background of necrosis |
Total tumor size- 7 × 4.5 cm Comprising anaplastic carcinoma, papillary carcinoma and follicular carcinoma |
Absent | Present | Died due to metastatic disease | ||
| Kim et al.13 (2014) | 67/F | USG- 4.4 cm heterogeneous iso-echoic nodule in the right thyroid and a 1.2 cm low-echoic nodule in the left thyroid |
Left lobe- Atypia of follicular cells with undetermined significance, Right lobe- Benign follicular nodule |
Right lobe, 4.3 cm |
Right lobe, 0.3 cm (Papillary microcarcinoma) Left lobe- Medullary carcinoma, 0.8 cm |
Absent | Absent | Disease free at follow up | |
| Abdullah et al.14 (2022) | 44/M | USG- Right thyroid lobe nodule measuring 35 × 27 × 25 mm suspicious for neoplasm | Follicular neoplasm | Follicular carcinoma with papillary thyroid carcinoma | - | - | No evidence of recurrence | ||
| 40/F | USG- A few small and solid nodules in both of the thyroid lobes, with the largest measuring 11 × 8 × 7 mm in the mid-third (TR3) of the left thyroid | Papillary thyroid carcinoma | Follicular carcinoma with papillary thyroid carcinoma | - | - | No evidence of recurrence | |||
| 37/F | USG- Left thyroid lobe solid nodule measuring 15 × 8 mm | Adenomatous follicular lesion | Follicular carcinoma with papillary thyroid carcinoma | - | - | No evidence of recurrence | |||
| 46/F | USG- Left thyroid gland solid nodule measuring 32 × 26 × 26 mm | - | Follicular carcinoma with papillary thyroid carcinoma | - | - | No evidence of recurrence | |||
| 40/F | USG- Right thyroid lobe solid nodule measuring 5 × 4 × 4 mm (TR4) and a left thyroid lobe small cystic nodule measuring 3 mm | - | Follicular carcinoma with papillary thyroid carcinoma | - | - | No evidence of recurrence | |||
| 55/F | USG- Right thyroid lobe mass (35 × 20 × 15 mm) | Follicular neoplasm | Follicular carcinoma with papillary thyroid carcinoma | - | - | Lost to follow -up | |||
| 31/F | - | Follicular neoplasm | Follicular carcinoma with papillary thyroid carcinoma | - | - | Lost to follow- up | |||
| Vlaenderen et al.15 (2020) | 12/F |
USG- A sharply defined hypervascular solid multilobular mass (Longest diameter 53 mm) with cystic components with microcalcifications in the left lobe |
- | Left lobe, 2.9 cm | Left lobe | - | Present | - | |
| Present case | 35/F | Computed tomography of neck showed a large solid nodule in right lobe of thyroid gland and isthmus with a dense calcific focus within and retrosternal extension. | Suspicious for papillary carcinoma |
Left, right lobe and isthmus; 6.7 × 4.5 × 3.5 cm. pT4 N0 |
Left lobe, 1.5 × 1 × 1 cm. pT2 N1 |
- | Present | No evidence of recurrence | |
The present case was a 35-year female who presented with a neck mass, and scalp metastasis. The previously reported cases have age ranging from 12 years to 67 years [6–15].
In most of the reported cases, the cytological diagnosis was a follicular neoplasm or atypia of undetermined significance [7, 10, 13, 14]. However, in the present case, fine needle aspiration cytology from the neck mass showed features suspicious of papillary carcinoma. This was similar to two previously reported cases by Abdelaal et al. and Abdullah et al. [7, 14].
None of the previously reported cases demonstrated lymph nodal metastasis by the papillary thyroid carcinoma component.
The origin of both these tumors is from follicular epithelial cells derived from medial endodermal analogue.16 The presence of synchronous medullary- papillary carcinoma may be associated with presence of RET protooncogene mutation. The FTC-PTC synchronicity may be explained by an origin from a common stem cell or a stimuli like radiation exposure [17]. The origin of these collision tumors may be explained by multifocal origin from different cell clones [18]. This may be the case where there is intervening normal thyroid tissue in between the two tumors as in the present case. A hostage theory is also suggested for the origin according to which the adenomatous areas are sequestrated by a new tumor type [19].
Synchronous detection of thyroid tumors can also occur as part of familial cancer syndromes like Cowden’s and Carney syndrome. However, no family history could be elicited in the present case.
Simultaneous detection of papillary and carcinoma as collision tumor very rare. The dual pathology makes the management complex. It is very essential for the clinician to be aware of such lesions to decide the best therapeutic interventions.
Author Contribution
Conceptualization: SA, PS, SZ. Data curation: SA, PS, AR. Formal analysis: SA, PS, SZ. Funding acquisition: Nil. Investigation: Methodology: Project administration: Resources: SZ. Software: Supervision: SZ. Validation: Visualization: SA, SZ. Writing – original draft: SA. Writing – review & editing: SZ. Approval of final manuscript: all authors.
Funding
None.
Declarations
Informed Consent
Informed patient consent was taken before publication of the article. Any identifying details (such as name, date of birth) of the patient will not be published.
Ethics Approval and Consent to Participate
Not applicable, because this article does not contain any studies with human or animal subjects.
Consent for Publication
Informed consent was sought from patient regarding participation and publication.
Competing Interests
The author(s) declared no potential conflicts of interest.
Footnotes
This paper has been prepared by the abovementioned authors and reviewed and agreed upon for submission. The requirements for authorship as stated above in this document have been met, and that each author believes that the manuscript represents honest work.
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