Synchronous cribriform morular variant of papillary and follicular carcinoma thyroid: A case series of a rare collision tumor

Zikki Hasan Fatima; Mohd Rafey; Nuzra Fazal; Kafil Akhtar

doi:10.4103/aort.aort_18_22

CASE SERIES

Year : 2022 | Volume : 2 | Issue : 2 | Page : 92-96

Synchronous cribriform morular variant of papillary and follicular carcinoma thyroid: A case series of a rare collision tumor

Zikki Hasan Fatima, Mohd Rafey, Nuzra Fazal, Kafil Akhtar
Department of Pathology, Faculty of Medicine, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India

Date of Submission	14-Jun-2022
Date of Decision	28-Jun-2022
Date of Acceptance	30-Jun-2022
Date of Web Publication	18-Nov-2022

Correspondence Address:
Dr. Kafil Akhtar
Department of Pathology, Faculty of Medicine, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aort.aort_18_22

Abstract

The synchronous presence of cribriform-morular variant of papillary thyroid carcinoma with follicular carcinoma is very rare. Collision tumors or the coexistence of histologically distinct malignant tumors in the same organ constitutes only 1.0% of all thyroid malignancies. The postulated hypothetical theories to the collision tumors are stem cell theory, collision theory, and hostage theory, which try to explain the synchronous association of these thyroid neoplasms. We report the case series of a synchronous cribriform-morular variant of papillary thyroid cancer and follicular thyroid carcinoma, which to our knowledge has not been reported till date.

Keywords: Carcinoma, cribriform papillary, follicular, synchronous, thyroid

How to cite this article:
Fatima ZH, Rafey M, Fazal N, Akhtar K. Synchronous cribriform morular variant of papillary and follicular carcinoma thyroid: A case series of a rare collision tumor. Ann Oncol Res Ther 2022;2:92-6

How to cite this URL:
Fatima ZH, Rafey M, Fazal N, Akhtar K. Synchronous cribriform morular variant of papillary and follicular carcinoma thyroid: A case series of a rare collision tumor. Ann Oncol Res Ther [serial online] 2022 [cited 2023 Mar 25];2:92-6. Available from: http://www.aort.info/text.asp?2022/2/2/92/361491

Introduction

Thyroid cancer is one of the most common endocrine tumors.^[1],[2] The synchronous or metachronous presence of two neoplasms is rare in the thyroid and presents a diagnostic and treatment challenge.^[3],[4] Hypotheses, such as stem cell theory, a single progenitor cell theory, and collision theory, have been used to explain the simultaneous occurrence of thyroid neoplasms of different cellular origins.^[3],[4]

Collision tumor is a term denoting two histologically distinct tumor types that occur at the same anatomic sites, which is a rare clinical entity.^[5] It is commonly seen in the liver, stomach, adrenal gland, ovary, lungs, kidneys, and colon.^[5] Collision tumors of the thyroid gland are very rare and constitute about only 1.0% of all thyroid malignancies.^[6] The most commonly reported combination is papillary thyroid carcinoma (PTC) with medullary thyroid carcinoma.^[7],[8],[9] We report a case series of a synchronous cribriform-morular variant of papillary thyroid cancer and follicular thyroid carcinoma (FTC), which to our knowledge has not been reported till date.

Case Reports

Case 1

A 30-year-old female presented to the surgery clinics with progressive anterior neck swelling for the past 5 years. There was no family history of similar neck mass or any history of irradiation. On local examination, a solitary movable mass was felt on the right lobe. The trachea was deviated to the left side, and bilateral cervical lymphadenopathy was present. Thyroid profile tests were found to be normal. Contrast-enhanced computed tomography neck showed a large heterogeneously enhancing solid cystic lesion in the right lobe of the thyroid with bilateral lymphadenopathy [Figure 1]. Fine-needle aspirate smear showed clusters of follicular epithelial cells with moderate anisonucleosis with coarse granular chromatin, indistinct nucleoli, irregular nuclear membrane, and scant eosinophilic cytoplasm, suggestive of follicular neoplasm [Figure 2]. Hence, a hemithyroidectomy with lymphadenectomy was performed.

Figure 1: Contrast-enhanced computed tomography neck showed a large heterogeneously enhancing solid cystic lesion in the right lobe of the thyroid with bilateral lymphadenopathy

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Figure 2: Fine-needle aspiration of the mass showed a high cellularity smear with cohesive clusters of atypical follicular epithelial cells with moderate anisonucleosis, coarse granular chromatin, indistinct nucleoli, irregular nuclear membrane, and scant eosinophilic cytoplasm, suggestive of a follicular neoplasm (H and E, ×10)

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Grossly, the resected specimen was globular, solid-cystic with foci of micropapillary excrescences, well encapsulated, and 7 cm × 5 cm × 2 cm in size [Figure 3]. Microscopically, tissue sections showed well-formed follicles with foci of solid areas with moderate cytological atypia of the lining epithelium [Figure 4]. Few areas showed papillary architecture with a cribriform pattern of growth with ground-glass nuclei and nuclear grooving in few cells [Figure 5]. Capsular and vascular invasion was evident with high mitotic activity. The isthmus and sampled lymph nodes were free of any tumor. A final diagnosis of follicular carcinoma with cribriform-morular variant of PTC was given. The patient was administered six cycles of 50 mg/m² cisplatin adjuvant chemotherapy and is doing well after 3 months of follow-up period.

Figure 3: Grossly the resected specimen was globular, solid-cystic with foci of micropapillary excrescences, well encapsulated, and 7 cm × 5 cm × 2 cm in size

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Figure 4: Microscopically, tissue sections showed well-formed follicles with foci of solid areas with moderate cytological atypia of the lining epithelium (H and E, ×40)

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Figure 5: Few areas showed papillary architecture with cribriform pattern of growth with ground glass nuclei and nuclear grooving in few cells (H and E, ×40)

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Case 2

A 35-year-old female presented to the surgery outpatient department with complaints of midline neck swelling for 5 months and pain for 25 days. There was no history of fever, dyspnea, dysphagia, and hoarseness of voice. On examination, the patient had a firm, tender midline neck mass of 5 cm × 3.5 cm in size, which moved freely with deglutition.

TSH was 1.15 μIU/L, free serum thyroxine (T₄) was 2.56 ng/dL, and free serum triiodothyronine (T₃) measured 4.4 pg/mL. Hematological parameters were unremarkable, and chest X-ray showed no abnormality. Ultrasound neck showed a solitary hypoechoic lesion in the right lobe of the thyroid.

Fine-needle aspiration cytology (FNAC) smear showed papillaroid configuration of follicular epithelial cells with mild-to-moderate anisonucleosis and scant cytoplasm, with occasional cohesive clusters of cells in acini [Figure 6]. Right lobectomy was performed. Grossly, a single brown, firm, encapsulated solid, globular mass of 7.2 cm × 5.3 cm × 2.4 cm size was seen. Microscopically focal areas of papillaroid and nested pattern, lined by pleomorphic cells with fine granular chromatin with cystic spaces filled with myxoid-like material were seen [Figure 7]. Variable-sized follicles lined by cells with marked cytologic atypia with foci of capsular and vascular invasion were also noted. Areas of necrosis and hemorrhage were noted along with high mitotic count. A final diagnosis of follicular carcinoma with cribriform variant of PTC was given. The patient was administered six cycles of 50 mg/m² cisplatin adjuvant chemotherapy. Our patient is doing well after 12 months of follow-up with no evidence of disease recurrence.

Figure 6: Fine-needle aspiration cytology smear showed papillaroid configuration of atypical follicular epithelial cells with mild-to-moderate anisonucleosis and scant cytoplasm, with occasional cohesive clusters of cells in acini (Papanicoalou stain, ×10)

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Figure 7: Microscopic examination showed focal areas of papillaroid and nested pattern, lined by pleomorphic cells with fine granular chromatin with cystic spaces filled with myxoid-like material (H and E, ×40)

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Case 3

A 45-year-old male reported to the surgical clinics with chief complaints of midline neck swelling for the past 2 years. The mass was not associated with pain, dysphagia, and hoarseness of voice. There was no history of fever and loss of appetite. On local examination, a well-defined cystic to solid, nontender mass of size 8 cm × 6 cm, was seen in the anterior part of the neck in the midline. The mass was fixed to the underlying structures, nonfluctuant, and moving with deglutition. No palpable neck nodes were seen.

X-ray chest was normal. Ultrasonography showed a lobulated mass with alternate hyper and hypoechoeic areas with foci of calcification. Routine hematologic investigations were unremarkable. FNAC showed few atypical cells admixed with cyst macrophages.

The mass was surgically excised. Grossly, the specimen was solid-cystic, gray-white with focal papillary excrescences, 6.4 cm × 4 cm × 3.1 cm in size with irregular capsule. Microscopic examination showed thyroid follicles of variable sizes, with atypical lining epithelial cells with hyperchromatic nucleus and minimal eosinophilic cytoplasm. Few epithelial cells showed ground-glass nuclei with clear chromatin. A background of cystic spaces with foci of calcification and myxoid change was also noted. A histopathologic impression of synchronous follicular and cribriform papillary carcinoma of the thyroid was given. 50 Gy of Co-60 radiotherapy and adjuvant chemotherapy with cisplatin 50 mg/m² × 6 cycles were administered. Our patient is doing well after 12 months of follow-up period.

Discussion

PTC and FTC are the two most common thyroid neoplasms having an endodermal derivative.^[10] PTC accounts for 70%–80% and follicular carcinoma comprises 5%–10% of all thyroid malignancies. PTC tends to have a predilection for lymphatic spread, while FTC tends to spread by hematogenous route.

Of the many variants of papillary carcinoma, cribriform-morular variant represents only 0.16% of the cases and occurs exclusively in females. It may be sporadic form or may be associated with familial adenomatous polyposis syndrome.^[11]

Multiple primary tumors originating in the same organ with distinctive and definitive features of malignancy are categorized into collision tumors, mixed tumors, and composite tumors.^[5] A collision tumor shows the presence of two histologically and morphologically distinct malignant tumors with no histological admixture, whereas a mixed tumor depicts a histological admixture of the two tumors.^{[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14]} Composite tumor contains two discrete cell populations such as thyroglobulin-positive papillary carcinoma cells and calcitonin-positive medullary carcinoma cells.^[13]

Collision tumors have been reported in the ovaries, colon, lung, stomach, skin, and kidneys but are extremely rare in the thyroid.^[5] The occurrence of PTC and FTC is very rarely seen.^[9] Most of the studies show the coexistence of papillary and medullary carcinomas.^[6],[7],[8]

The various hypotheses put forward to explain the simultaneous occurrence of thyroid neoplasms of different cell types are stem cell theory, collision theory, and hostage theory.^{[10],[15],[16],[17]} The stem cell theory postulates that cancer stem cells have the ability to differentiate into different tumor cell lines in the same organ or anatomic site.^[18] Collision theory states that the tumors are polyclonal and express different genetic alterations in each component of the tumor.^[17] The hostage or the neoplastic coercion theory asserts that the normal thyroid follicles get entrapped within a medullary thyroid carcinoma, get influenced by the host microenvironment, become hyperplastic, and finally convert into a malignant neoplasm.^[19],[20]

Contrary to the above-described views, the synchronicity of the tumors is considered to be merely coincidental with no genetic association.^[21] It has been reported that follicular carcinoma does not show any substantial association with BRAF and RET oncogene rearrangement.^[22] Only 25.0% of medullary carcinoma have RET proto-oncogene mutation similar to papillary carcinoma. The more common occurrence of sporadic medullary carcinoma also defies any genetic linkage in the pathogenesis of the coexistence of dual tumors.^[23] Immunohistochemically, the tumor cells are positive for cytokeratin 19 and beta-catenin. The cribriform component shows positivity for TTF1 and negativity for thyroglobulin. Morulae are positive for keratin 5 and CD5 and negative for calcitonin, Galectin-3, chromogranin A, synaptophysin, CD56, p63, p40, TTF1, and PAX8.^[24],[25] Molecular studies revealed germline APC mutations few tumors.^[24]

The dual pathology and scarcity of literature on the collision tumor often contribute to a complicated management plan. It has been suggested that each component of the combination should be treated like an independent primary and the treatment should be guided by the more aggressive neoplasm. A patient-specific treatment plan involving surgical management with adjunct therapy is recommended.^[26]

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.

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