Tag: thyroid

Invasive fibrous thyroiditis (IgG₄-related thyroiditis; Riedel thyroiditis)

Invasive fibrous thyroiditis is a rare form of chronic thyroiditis on the spectrum of IgG₄-related diseases, characterized by extensive fibrosis and increased IgG₄-expressing plasma cells.  The cause is unknown.  Any number of organ systems may be involved by this process, most notably the pancreas.  When the thyroid gland is affected, extensive replacement of the glandular tissue by fibrosis is seen histologically.  Up to one third of patients with invasive fibrous thyroiditis will experience IgG₄-related disease in another organ. 

The condition is seen more often in women, usually in the 5^th decade.  There is an association with cigarette-smoking.  Patients usually present with a very firm goiter, often with compressive symptoms.  Extensive fibrosis may damage the recurrent laryngeal nerve, causing vocal cord paralysis and hoarseness.  The sympathetic trunk may also be affected, resulting in Horner syndrome.  Occlusion of blood vessels and destruction of parathyroid glands may occur.  Invasive fibrous thyroiditis may mimic malignancy clinically due to infiltration of the fibrosis into the soft tissues of the neck. 

Microscopic examination reveals fibrosis overtaking the thyroid gland in broad hypocellular zones, with associated patchy chronic inflammation.  Some residual atrophic thyroid follicles may remain, but extensive fibrous replacement is typical.  Extension into the soft tissue and strap muscles results in fixation of the mass.  Occlusive phlebitis (characteristic of IgG₄-related disease), or fibrosis and inflammation of small and medium veins, is noted in most cases.

Elevated serum IgG₄ levels are present only in about 50% of patients, and this finding is not specific to invasive fibrous thyroiditis, so it is of somewhat limited diagnostic value.  Immunohistochemistry for IgG and IgG₄ is helpful if it demonstrates an increased ratio of IgG₄ to IgG-expressing plasma cells: a ratio of greater than 40% is supportive of this diagnosis.  Hypothyroidism and/or hypoparathyroidism are typical sequelae of invasive fibrous thyroiditis. 

While it may act aggressively, invasive fibrous thyroiditis is a benign condition and does not always require surgical treatment.  Medical management of hypothyroidism and/or hypoparathyroidism is needed in affected patients.  Patients should be monitored for manifestations of IgG₄-related disease in other organ systems, as systemic involvement is associated with significant morbidity and mortality.  Corticosteroid therapy is useful in such situations.

References

• Falhammar H, Juhlin CC, Barner C, Catrina SB, Karefylakis C, Calissendorff J. Riedel’s thyroiditis: clinical presentation, treatment and outcomes. Endocrine. 2018;60(1):185-192. doi:10.1007/s12020-018-1526-3
• Mammen SV, Gordon MB. SUCCESSFUL USE OF RITUXIMAB IN A CASE OF RIEDEL THYROIDITIS RESISTANT TO TREATMENT WITH PREDNISONE AND TAMOXIFEN. AACE Clin Case Rep. 2019;5(3):e218-e221. Published 2019 Apr 25. doi:10.4158/ACCR-2018-0352
• Darouichi M, Constanthin PE. Riedel’s thyroiditis. Radiol Case Rep. 2016;11(3):175-177. Published 2016 Jun 17. doi:10.1016/j.radcr.2016.05.017
• Thompson LDR, Bishop JA.  (2019).  Head and Neck Pathology, 3^rd edition, pp 557-561.  Philadelphia, PA: Elsevier.

Quiz Answers

Q1 = C. Serum IgG₄

Q2 = D. Occlusive phlebitis

Poorly Differentiated Thyroid Carcinoma.

Poorly differentiated thyroid carcinoma (PDTC) is a clinically aggressive follicular cell derived neoplasm that represents approximately 1% of all thyroid malignancies. The 10-year patient survival (60-70%) is intermediate between differentiated and anaplastic thyroid carcinomas.

The most widely accepted definition of PDTC is the laid out in the Turin criteria, which were adopted by the World Health Organization Classification of Tumours of the Endocrine Organs in 2017. According to the Turin criteria, PDTC is defined as a tumor with solid, trabecular, or insular growth that lacks papillary nuclear features and has at least one of the following: ≥ 3 mitoses per 10 high power fields, tumor necrosis, or convoluted nuclei. There is some evidence that the Turin criteria can be applied to Hurthle cell (oncocytic) tumors as well.

The overwhelming majority of PDTCs occur in older adults (mean patient age of 60 years); they are exceedingly rare in childhood or adolescence. However, PDTCs that do occur in younger persons have unique features. They primarily affect teenagers and frequently harbor DICER1 mutations, which may be associated with hereditary DICER1 syndrome in a subset of cases. DICER1 mutations are very rare in adult PDTC, which often harbor driver mutations common in differentiated thyroid carcinomas (BRAF, NRAS, etc…). These mutations have not been found in pediatric PDTC.

While the prognosis of differentiated thyroid carcinoma is more favorable in younger persons compared to older adults, the same is not true for PDTC. PDTC in the young (< 21 years) is still an aggressive tumor type. Although data is limited, survival rates are likely similar to those in older adults. Prognostic features remain to be characterized but disease extent may be important. Large tumor size and extrathyroidal extension with positive resection margins may be associated with worse outcomes compared to more limited tumors or tumors with encapsulation.

References

• Asioli S, Erickson LA, Righi A, et al. Poorly differentiated carcinoma of the thyroid: validation of the Turin proposal and analysis of IMP3 expression. Mod. Pathol. 2010;23:1269–1278.
• Ibrahimpasic T, Ghossein R, Carlson DL, et al. Outcomes in patients with poorly differentiated thyroid carcinoma. J. Clin. Endocrinol. Metab. 2014;99:1245–1252.
• Volante M, Collini P, Nikiforov YE, et al. Poorly differentiated thyroid carcinoma: the Turin proposal for the use of uniform diagnostic criteria and an algorithmic diagnostic approach. Am. J. Surg. Pathol. 2007;31:1256–1264.
• Tallini G, Asioli S, Aubert S, et al. Poorly differentiated thyroid carcinoma. In: WHO Classification of Tumours of Endocrine Organs. 4th ed. Lyon: International Agency for Research on Cancer; 2017.
• Chernock RD, Rivera B, Borrelli N, Hill DA, Fahiminiya S, Shah T, Chong AS, Aqil B, Mehrad M, Giordano TJ, Sheridan R, Rutter MM, Dehner LP, Foulkes WD, Nikiforov YE. Poorly differentiated thyroid carcinoma of childhood and adolescence: a distinct entity characterized by DICER1 mutations. Mod. Pathol. Epub ahead of print.
• Hill DA, Ivanovich J, Priest JR, et al. DICER1 mutations in familial pleuropulmonary blastoma. Science 2009;325:965.

Quiz Answers

Q1 = B. DICER1

Q2 = B. False

Secretory Carcinoma of the Thyroid.

Salivary gland secretory carcinoma (SC), previously known as mammary analog secretory carcinoma, is a relatively rare neoplasm and is defined by the presence of a recurrent balanced translocation t(12:15) resulting in fusion of the ETV6 gene. These tumors were named as such due to their histologic resemblance to SC of the breast.

SC has been reported in multiple extra-salivary locations including thyroid gland and skin. Less than 20 cases of SC in the thyroid have previously been reported in the literature. The average age of presentation is 59 years (range 36–74 years) and it has a strong female predominance.

Histologically, they have a mixed microcystic, tubular, trabecular, papillary/pseudopapillary and solid growth pattern with densely hyalinized and fibrotic stroma and eosinophilic to lightly basophilic intraluminal secretions. The tumor cells are polygonal and generally uniform with low to medium nuclear-to-cytoplasmic ratio. Cytoplasm is abundant and eosinophilic and ranges from granular to bubbly or vacuolated. Nuclei are round to ovoid with vesicular chromatin. Nuclear grooves and membrane irregularities may be prominent. Pseudoinclusions are rare, but may be seen. Nucleoli are generally single, prominent and centrally located and may be eosinophilic. Necrosis and increased mitotic activity can be seen in these tumors.

All cases of SC of the thyroid are negative for TTF-1 and Thyroglobulin while positive for mammaglobin. The majority are S100 and GATA3 positive though staining may be patchy and of variable intensity. PAX8 immunoreactivity has been reported in 90% of cases and is frequently focal and weak (Figure 6). Intraluminal secretions are positive for periodic-acid Schiff (with and without diastase) and for mucicarmine. FISH using break-apart probe for ETV6 or PCR with ETV6 and NTRK3 can be used to confirm morphologic suspicion.

Adjuvant therapy with radioactive iodine would not be effective since the tumors do not have follicular differentiation.

References

• Dettloff J, Seethala RR, Stevens TM, et al. Mammary Analog Secretory Carcinoma (MASC) Involving the Thyroid Gland: A Report of the First 3 Cases. Head Neck Pathol. 2017;11(2):124–130. doi:10.1007/s12105-016-0741-6
• Dogan S, Wang L, Ptashkin RN, et al. Mammary analog secretory carcinoma of the thyroid gland: A primary thyroid adenocarcinoma harboring ETV6-NTRK3 fusion. Mod Pathol. 2016;29(9):985–995. doi:10.1038/modpathol.2016.115
• Reynolds S, Shaheen M, Olson G, Barry M, Wu J, Bocklage T. A Case of Primary Mammary Analog Secretory Carcinoma (MASC) of the Thyroid Masquerading as Papillary Thyroid Carcinoma: Potentially More than a One Off. Head Neck Pathol. 2016;10(3):405–413. doi:10.1007/s12105-016-0715-8

Quiz Answers

Q1 = A. t(12;15)(p13,q25) ETV6-NTRK3

Q2 = B. False