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Thyroid pathology
SELF-ASSESSMENT
Thyroid pathology Questions Question 1 A 29-year-old female presented with a smooth mass, which was found to be intrathyroidal, in the right side of her neck. Ultrasound scan showed a solid encapsulated nodule. Fine needle aspiration cytology was performed under ultrasound guidance. This gave an inadequate population of follicular epithelial cells together with some thin colloid, and was reported in the Thy1 category. Three weeks later, upon her return, a further fine needle aspiration was performed. This showed a satisfactory population of follicular epithelial cells, including some microfollicular fragments and some colloid. This was reported in the Thy3f category. Following MDT discussion, thyroid lobectomy was recommended and she underwent this 3 weeks after the second fine needle aspirate. A 28 mm encapsulated nodule was found, and all of its capsule was blocked out. Figures 1 and 2 are areas of the capsule. Figures 3 and 4 are adjacent to the capsule. (a) What diagnosis or differential diagnosis should be offered on the capsule represented in Figures 1 and 2? (b) What diagnosis or differential diagnosis should be offered on the adjacent thyroid tissue shown in Figures 3 and 4?
Figure 2
Figure 3
Figure 1
Timothy J Stephenson is a Consultant Histopathologist and Clinical Director of Laboratory Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital, Sheffield, UK. Conflicts of interest: none declared.
DIAGNOSTIC HISTOPATHOLOGY 17:11
Figure 4
505
Ó 2011 Elsevier Ltd. All rights reserved.
SELF-ASSESSMENT
Question 2 A 48-year-old male presented with an intrathyroidal mass in the left lobe of the thyroid, which he said had been apparent for 8 months. Ultrasound scan showed a 45 mm diameter partially encapsulated nodule. Fine needle aspiration cytology, performed under ultrasound guidance, was suspicious of papillary carcinoma, Thy4 category. Following MDT discussion he underwent thyroid lobectomy. (a) What tissue elements are present in Figures 5e7 and what is the diagnosis? (b) Figure 8 shows cytokeratin 19 immunohistochemistry on this lesion. What is the significance of this finding? (c) What are the value and limitations of cytokeratin 19 immunohistochemistry in relation to thyroid tumours? Figure 7
Figure 5
Figure 8 High power immunohistochemistry for Ck 19.
Question 3 A 51-year-old male presented with a right thyroid mass, which he said had been present for many years, but which had been enlarging over the last 6 weeks. Ultrasound scan showed an encapsulated nodule. Fine needle aspiration cytology showed a pure population of Hurthle cells with scanty colloid and no inflammatory cells, Thy3f category. Thyroid lobectomy was subsequently performed. (a) What is the significance of the Thy3f category? (b) What are the limitations of a Thy3f cytological diagnosis? (c) What further investigations can be done? (d) What is the diagnosis (Figures 9e12)?
Figure 6
DIAGNOSTIC HISTOPATHOLOGY 17:11
506
Ó 2011 Elsevier Ltd. All rights reserved.
SELF-ASSESSMENT
Figure 9
Figure 12
Answers Answer 1 (a) The breached capsule is likely to be either capsular penetration by follicular thyroid cancer or a post-FNA artefact, more likely the latter on the basis of these images. (b) Figure 3 shows a space lined by foamy macrophages e probably the more recent FNA tract with initial healing and repair. Figure 4 shows a stellate scar. This needs examining at higher power to see whether it is just a scar caused by the first FNA, or whether it contains any papillary cancer type epithelium in which case it would be a papillary microcarcinoma. Discussion Fine needle aspiration cytology may cause a range of artefacts that mimic neoplasia, with the collective name Worrisome Histological Alterations Following Fine Needle Aspiration of the Thyroid, coined by Professor Virginia LiVolsi, which is often abbreviated to WHAFFT. These include, principally, perforations of the capsule as shown in Figures 1 and 2, which may contain follicles. Key to recognition of the artefact is the demonstration of inflammation (Figure 1), cholesterol crystals (Figure 2) or haemosiderin. The follicular epithelium only reaches the external aspect of the capsule and does not grow in a mushroom shape or “collar stud” lesion beyond it. Another clue to the artefact is spotting a needle tract in the thyroid parenchyma nearby, as in Figure 3. After about 6 weeks, this heals by fibrosis and can leave a stellate scar, which can entrap epithelium and which, at low power, can mimic a papillary microcarcinoma. Granulation tissue after FNA can also have atypical spindle cells of endothelial or fibroblastic origin, which can mimic a range of other neoplasms. For a diagnosis of follicular carcinoma (which is the key differential diagnosis of the type of WHAFFT shown in Figures 1 and 2), full thickness capsular transgression with or without vascular invasion in or beyond the capsule are
Figure 10
Figure 11
DIAGNOSTIC HISTOPATHOLOGY 17:11
507
Ó 2011 Elsevier Ltd. All rights reserved.
SELF-ASSESSMENT
the absolute defining features. Since this is an architectural feature which may not be evident until many blocks are examined, frozen section is not recommended in the diagnosis of follicular thyroid lesions. Subdivision into minimally invasive and widely invasive subtypes (obvious macroscopic invasion) is prognostically useful, as is grading. Beware the rare non-encapsulated variant which may be widely invasive without any capsule in which to “see” the invasion. Where nuclear features of papillary carcinoma are also present in a follicular patterned carcinoma, the diagnosis becomes that of follicular variant papillary carcinoma, which metastasizes as for papillary carcinoma. True vascular invasion must be distinguished from impaction of tumour cells into vessels at cut-up. Elastin stains and immunohistochemistry for endothelial markers are possibly over-rated because true vascular invasion is generally apparent without their use. Aberrant cytological features, necrosis and vascular invasion within the tumour confined by the capsule point to a diagnosis of “atypical adenoma”. These have a benign course. Over-diagnosis of follicular neoplasms is a risk if the features of hyperplastic nodules in multinodular goitre are overlooked.
The colloid is thick and has a scalloped edge. The capsule is penetrated, with clear-cut growth of neoplasm beyond its original contour. The features are diagnostic of well differentiated follicular variant papillary thyroid carcinoma, with at least one focus of definite capsular invasion. (b) Cytokeratin 19 expression substantiates a diagnosis of papillary carcinoma. (c) The value of Ck 19 immunohistochemistry in relation to thyroid tumours is that Ck 19 is expressed by papillary cancer and its variants. The principal limitation is that foci of Ck 19 positivity are common in thyroiditis. € rthle cell tumours show Another problem is that Hu apparent staining with Ck 19, especially if the avidine biotin technique is used, but this staining may be nonspecific. Discussion Full-thickness capsular transgression is present here, indicating that if this had been a pure follicular neoplasm, it would have been a case of minimally invasive follicular carcinoma. However, this case shows oval nuclei, nuclear clearing and overlapping of a degree which, coupled with scalloping of the thick colloid, establishes the diagnosis of follicular variant papillary thyroid carcinoma (FVPTC). The diagnosis of FVPTC can also be assisted by Ck 19, and high molecular weight Ck positivity on immunohistochemistry. FVPTC is traditionally diagnosed on the basis of the nuclear features of papillary carcinoma. Care should be taken that the nuclear features are authentic e in particular the nuclei need to be oval and grooved; they are best seen at the periphery of the lesion. Cleared round nuclei without grooves in a poorly fixed centre of a nodule do not count towards a diagnosis of FVPTC. The traditional view is that it does not need to invade the capsule to be malignant, but prognosis is so exceptionally good in encapsulated cases, where the capsule is not penetrated and there is no vascular invasion in an adequately sampled case, that some authors now advocate regarding encapsulated non-invasive FVPTC as equivalent to a follicular adenoma only. Indeed, there is emerging molecular evidence that these tumours have more in common with follicular adenoma than with invasive papillary carcinomas.
FURTHER READING Baloch ZW, LiVolsi VA. Post fine-needle aspiration histologic alterations of thyroid revisited. Am J Clin Pathol 1999; 112: 311e16. Baloch ZW, LiVolsi VA. Our approach to follicular-patterned lesions of the thyroid. J Clin Pathol 2007; 60: 244e50. LiVolsi VA, Merino MJ. Worrisome histologic alterations following fine-needle aspiration of the thyroid (WHAFFT). Pathol Ann 1994; 29: 99e120. LiVolsi VA. Well differentiated thyroid carcinoma. Clin Oncol 1996; 8: 281e88. Lloyd RV, Douglas BR, Young WF. Endocrine diseases. Fascicle 1. In: Atlas of nontumor pathology. Washington: American Registry of Pathology and Armed Forces Institute of Pathology, 2002. Polyzos SA, Patsiaoura K, Zachou K. Histological alterations following thyroid fine needle biopsy: a systematic review. Diagn Cytopathol 2009; 37: 455e65. Rosai J, Kuhn E, Carcangiu ML. Pitfalls in thyroid tumour pathology. Histopathology 2006; 49: 107e20. Sobrinho-Simoes M, Eloy C, Magalhaes J, Lobo C, Amaro T. Follicular thyroid carcinoma. Mod Pathol 2011; 24: S10e18. Stephenson TJ. Endocrine. Chapter 1. In: Al-Sam S, Lakhani SR, Davies JD, eds. A practical atlas of pseudomalignancy. London: Edward Arnold, 1998: 1e19.
FURTHER READING Al-Brahim N, Asa SL. Papillary thyroid carcinoma: an overview. Arch Pathol Lab Med 2006; 130: 1057e62. Pinto Couto J, Prazeres H, Castro P, et al. How molecular pathology is changing and will change the therapeutics of patients with follicular cell-derived thyroid cancer. J Clin Pathol 2009; 62: 414e21. Prasad ML, Pellegata NS, Huang Y, Nagaraja HN, de la Chapelle A, Kloos RT. Galectin-3, fibronectin-1, CITED-1, HBME1 and cytokeratin-19 immunohistochemistry is useful for the differential diagnosis of thyroid tumors. Mod Pathol 2005; 18: 48e57. Rosai J. The encapsulated follicular variant of papillary carcinoma: back to the drawing board. Endocr Pathol 2010; 21: 7e11.
Answer 2 (a) The cells are cuboidal but a little taller than normal thyroid epithelium. The nuclei are oval, grooved, partially overlapping, and have some central clearing.
DIAGNOSTIC HISTOPATHOLOGY 17:11
508
Ó 2011 Elsevier Ltd. All rights reserved.
SELF-ASSESSMENT
comprising these cells were of unpredictable behaviour and € rthle cell “tumours”. It is now known should be termed Hu that the defining criteria for malignancy are exactly the same as for follicular neoplasms in general. € rthle cell tumours are more likely than ordinary Hu follicular neoplasms to show invasion and thorough € rthle cell neoplasms is therefore important. sampling of Hu They are also more likely to show tumour necrosis. Any cystic necrotic thyroid tumour should be carefully searched € rthle cell elements. for Hu They are generally considered to be a little more aggressive than standard follicular carcinoma and, unlike it, may metastasize to lymph nodes. Those that metastasize to lymph nodes may well be in effect papillary carcinomas, not recognized as such because the nuclear features are not well € rthle cell developed. The somewhat poorer prognosis of Hu carcinomas may be because their uptake of radio-iodine is often low. The finding of apparent follicular carcinoma in a lymph node should always prompt consideration that it may be 1) follicular variant papillary carcinoma or 2) € rthle cell carcinoma. Hu € rthle cell tumours needs to Immunohistochemistry of Hu be interpreted with caution, due to non-specific uptake, particularly when the avidinebiotin technique is used.
Sobin LH, Gospodarowicz MK, Wittekind C. UICC TNM classification of malignant tumours, 7th edn. Wiley-Blackwell, 2009. Stephenson TJ. Papillary carcinoma of the thyroid: a tumour still with no benign neoplastic counterpart. Histopathology 2001; 39: 536e38. Stephenson TJ. Prognostic and predictive factors in endocrine neoplasia. Histopathology 2006; 48: 629e43. Stephenson TJ, Johnson SJ. Dataset for thyroid cancer histopathology reports. London: RCPath, 2010.
Answer 3 (a) The significance of the Thy3f category is that a follicular neoplasm cannot be excluded. (b) The limitations of a Thy3f cytological diagnosis are that it is not possible to predict where the neoplasm will be benign or malignant. This is because cellular follicular nodules in multinodular goitre, follicular adenomas and follicular carcinomas may all give the same appearance of a population of follicular epithelial cells not accompanied by other features that point towards a benign diagnosis. (c) There are no further cytological investigations that can be done (although it is hoped that 1 day molecular biology, including proteomics, may assist the differential diagnosis) and investigation of the nodule usually requires histology of the nodule, excised by hemithyroidectomy. This is because the diagnosis of follicular carcinoma, including its oncocytic variant, rests on architectural features such as capsular and/or vascular invasion. (d) Figure 9 shows basically solid/follicular architecture, € rthle but nearly all the cells (by definition >80%) are Hu cells, equipped with granular eosinophilic cytoplasm and large nuclei with large eosinophilic central nucleoli, € rthle cell neoplasm. The apparent nuclear signifying a Hu pleomorphism and enlargement is common for € rthle cell neoplasm and does not have any implia Hu cation of whether it is malignant or not. Figure 10 shows vascular invasion within the capsule while Figure 11 shows full thickness capsular transgression by tumour, € rthle cell carcinoma. Finally, indicating that this is Hu Figure 12 shows widespread invasion of the original thyroid capsule with extension of the cancer into perithyroidal soft tissues indicating a pT3 tumour at least according to TNM version 7. The carcinoma may be incompletely excised, R1 resection, at this point.
FURTHER READING Asa SL. My approach to oncocytic tumours of the thyroid. J Clin Pathol 2004; 57: 225e32. Cross P, Chandra A, Giles T, et al. Guidance on the reporting of thyroid cytology specimens. London: RCPath, 2009. Guidelines for the management of thyroid cancer, 2nd edn. British Thyroid Association and Royal College of Physicians, 2007. Montone KT, Balock ZW, LiVolsi VA. The thyroid Hurthle (oncocytic) cell and its associated pathologic conditions: a surgical pathology and cytopathology review. Arch Pathol Lab Med 2008; 132: 1241e50. Stephenson TJ. Pathological spectrum of thyroid disease. Chapter 2. In: Arora A, Tolley N, Tuttle RM, eds. Practical manual of thyroid and parathyroid disease. Oxford: Blackwell Publishing, 2010: 14e24. Tallini G, Carcangiu ML, Rosai J. Oncocytic neoplasms of the thyroid gland (Review). Acta Path Jap 1992; 42: 305e15. Thompson LDR, ed. Endocrine pathology. Philadelphia: Elsevier, 2006: 351e57. €rthle Vodanovic S, Crepinko I, Smoje J. Morphologic diagnosis of Hu cell tumors of the thyroid gland. Acta Cytol 1993; 37: 317e22.
Discussion € rthle cells have voluminous eosinophilic cytoplasm rich Hu in mitochondria, as evidenced by special stains and electron microscopy. It was once thought that thyroid neoplasms
DIAGNOSTIC HISTOPATHOLOGY 17:11
509
Ó 2011 Elsevier Ltd. All rights reserved.
Thyroid pathology Questions Question 1 A 29-year-old female presented with a smooth mass, which was found to be intrathyroidal, in the right side of her neck. Ultrasound scan showed a solid encapsulated nodule. Fine needle aspiration cytology was performed under ultrasound guidance. This gave an inadequate population of follicular epithelial cells together with some thin colloid, and was reported in the Thy1 category. Three weeks later, upon her return, a further fine needle aspiration was performed. This showed a satisfactory population of follicular epithelial cells, including some microfollicular fragments and some colloid. This was reported in the Thy3f category. Following MDT discussion, thyroid lobectomy was recommended and she underwent this 3 weeks after the second fine needle aspirate. A 28 mm encapsulated nodule was found, and all of its capsule was blocked out. Figures 1 and 2 are areas of the capsule. Figures 3 and 4 are adjacent to the capsule. (a) What diagnosis or differential diagnosis should be offered on the capsule represented in Figures 1 and 2? (b) What diagnosis or differential diagnosis should be offered on the adjacent thyroid tissue shown in Figures 3 and 4?
Figure 2
Figure 3
Figure 1
Timothy J Stephenson is a Consultant Histopathologist and Clinical Director of Laboratory Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital, Sheffield, UK. Conflicts of interest: none declared.
DIAGNOSTIC HISTOPATHOLOGY 17:11
Figure 4
505
Ó 2011 Elsevier Ltd. All rights reserved.
SELF-ASSESSMENT
Question 2 A 48-year-old male presented with an intrathyroidal mass in the left lobe of the thyroid, which he said had been apparent for 8 months. Ultrasound scan showed a 45 mm diameter partially encapsulated nodule. Fine needle aspiration cytology, performed under ultrasound guidance, was suspicious of papillary carcinoma, Thy4 category. Following MDT discussion he underwent thyroid lobectomy. (a) What tissue elements are present in Figures 5e7 and what is the diagnosis? (b) Figure 8 shows cytokeratin 19 immunohistochemistry on this lesion. What is the significance of this finding? (c) What are the value and limitations of cytokeratin 19 immunohistochemistry in relation to thyroid tumours? Figure 7
Figure 5
Figure 8 High power immunohistochemistry for Ck 19.
Question 3 A 51-year-old male presented with a right thyroid mass, which he said had been present for many years, but which had been enlarging over the last 6 weeks. Ultrasound scan showed an encapsulated nodule. Fine needle aspiration cytology showed a pure population of Hurthle cells with scanty colloid and no inflammatory cells, Thy3f category. Thyroid lobectomy was subsequently performed. (a) What is the significance of the Thy3f category? (b) What are the limitations of a Thy3f cytological diagnosis? (c) What further investigations can be done? (d) What is the diagnosis (Figures 9e12)?
Figure 6
DIAGNOSTIC HISTOPATHOLOGY 17:11
506
Ó 2011 Elsevier Ltd. All rights reserved.
SELF-ASSESSMENT
Figure 9
Figure 12
Answers Answer 1 (a) The breached capsule is likely to be either capsular penetration by follicular thyroid cancer or a post-FNA artefact, more likely the latter on the basis of these images. (b) Figure 3 shows a space lined by foamy macrophages e probably the more recent FNA tract with initial healing and repair. Figure 4 shows a stellate scar. This needs examining at higher power to see whether it is just a scar caused by the first FNA, or whether it contains any papillary cancer type epithelium in which case it would be a papillary microcarcinoma. Discussion Fine needle aspiration cytology may cause a range of artefacts that mimic neoplasia, with the collective name Worrisome Histological Alterations Following Fine Needle Aspiration of the Thyroid, coined by Professor Virginia LiVolsi, which is often abbreviated to WHAFFT. These include, principally, perforations of the capsule as shown in Figures 1 and 2, which may contain follicles. Key to recognition of the artefact is the demonstration of inflammation (Figure 1), cholesterol crystals (Figure 2) or haemosiderin. The follicular epithelium only reaches the external aspect of the capsule and does not grow in a mushroom shape or “collar stud” lesion beyond it. Another clue to the artefact is spotting a needle tract in the thyroid parenchyma nearby, as in Figure 3. After about 6 weeks, this heals by fibrosis and can leave a stellate scar, which can entrap epithelium and which, at low power, can mimic a papillary microcarcinoma. Granulation tissue after FNA can also have atypical spindle cells of endothelial or fibroblastic origin, which can mimic a range of other neoplasms. For a diagnosis of follicular carcinoma (which is the key differential diagnosis of the type of WHAFFT shown in Figures 1 and 2), full thickness capsular transgression with or without vascular invasion in or beyond the capsule are
Figure 10
Figure 11
DIAGNOSTIC HISTOPATHOLOGY 17:11
507
Ó 2011 Elsevier Ltd. All rights reserved.
SELF-ASSESSMENT
the absolute defining features. Since this is an architectural feature which may not be evident until many blocks are examined, frozen section is not recommended in the diagnosis of follicular thyroid lesions. Subdivision into minimally invasive and widely invasive subtypes (obvious macroscopic invasion) is prognostically useful, as is grading. Beware the rare non-encapsulated variant which may be widely invasive without any capsule in which to “see” the invasion. Where nuclear features of papillary carcinoma are also present in a follicular patterned carcinoma, the diagnosis becomes that of follicular variant papillary carcinoma, which metastasizes as for papillary carcinoma. True vascular invasion must be distinguished from impaction of tumour cells into vessels at cut-up. Elastin stains and immunohistochemistry for endothelial markers are possibly over-rated because true vascular invasion is generally apparent without their use. Aberrant cytological features, necrosis and vascular invasion within the tumour confined by the capsule point to a diagnosis of “atypical adenoma”. These have a benign course. Over-diagnosis of follicular neoplasms is a risk if the features of hyperplastic nodules in multinodular goitre are overlooked.
The colloid is thick and has a scalloped edge. The capsule is penetrated, with clear-cut growth of neoplasm beyond its original contour. The features are diagnostic of well differentiated follicular variant papillary thyroid carcinoma, with at least one focus of definite capsular invasion. (b) Cytokeratin 19 expression substantiates a diagnosis of papillary carcinoma. (c) The value of Ck 19 immunohistochemistry in relation to thyroid tumours is that Ck 19 is expressed by papillary cancer and its variants. The principal limitation is that foci of Ck 19 positivity are common in thyroiditis. € rthle cell tumours show Another problem is that Hu apparent staining with Ck 19, especially if the avidine biotin technique is used, but this staining may be nonspecific. Discussion Full-thickness capsular transgression is present here, indicating that if this had been a pure follicular neoplasm, it would have been a case of minimally invasive follicular carcinoma. However, this case shows oval nuclei, nuclear clearing and overlapping of a degree which, coupled with scalloping of the thick colloid, establishes the diagnosis of follicular variant papillary thyroid carcinoma (FVPTC). The diagnosis of FVPTC can also be assisted by Ck 19, and high molecular weight Ck positivity on immunohistochemistry. FVPTC is traditionally diagnosed on the basis of the nuclear features of papillary carcinoma. Care should be taken that the nuclear features are authentic e in particular the nuclei need to be oval and grooved; they are best seen at the periphery of the lesion. Cleared round nuclei without grooves in a poorly fixed centre of a nodule do not count towards a diagnosis of FVPTC. The traditional view is that it does not need to invade the capsule to be malignant, but prognosis is so exceptionally good in encapsulated cases, where the capsule is not penetrated and there is no vascular invasion in an adequately sampled case, that some authors now advocate regarding encapsulated non-invasive FVPTC as equivalent to a follicular adenoma only. Indeed, there is emerging molecular evidence that these tumours have more in common with follicular adenoma than with invasive papillary carcinomas.
FURTHER READING Baloch ZW, LiVolsi VA. Post fine-needle aspiration histologic alterations of thyroid revisited. Am J Clin Pathol 1999; 112: 311e16. Baloch ZW, LiVolsi VA. Our approach to follicular-patterned lesions of the thyroid. J Clin Pathol 2007; 60: 244e50. LiVolsi VA, Merino MJ. Worrisome histologic alterations following fine-needle aspiration of the thyroid (WHAFFT). Pathol Ann 1994; 29: 99e120. LiVolsi VA. Well differentiated thyroid carcinoma. Clin Oncol 1996; 8: 281e88. Lloyd RV, Douglas BR, Young WF. Endocrine diseases. Fascicle 1. In: Atlas of nontumor pathology. Washington: American Registry of Pathology and Armed Forces Institute of Pathology, 2002. Polyzos SA, Patsiaoura K, Zachou K. Histological alterations following thyroid fine needle biopsy: a systematic review. Diagn Cytopathol 2009; 37: 455e65. Rosai J, Kuhn E, Carcangiu ML. Pitfalls in thyroid tumour pathology. Histopathology 2006; 49: 107e20. Sobrinho-Simoes M, Eloy C, Magalhaes J, Lobo C, Amaro T. Follicular thyroid carcinoma. Mod Pathol 2011; 24: S10e18. Stephenson TJ. Endocrine. Chapter 1. In: Al-Sam S, Lakhani SR, Davies JD, eds. A practical atlas of pseudomalignancy. London: Edward Arnold, 1998: 1e19.
FURTHER READING Al-Brahim N, Asa SL. Papillary thyroid carcinoma: an overview. Arch Pathol Lab Med 2006; 130: 1057e62. Pinto Couto J, Prazeres H, Castro P, et al. How molecular pathology is changing and will change the therapeutics of patients with follicular cell-derived thyroid cancer. J Clin Pathol 2009; 62: 414e21. Prasad ML, Pellegata NS, Huang Y, Nagaraja HN, de la Chapelle A, Kloos RT. Galectin-3, fibronectin-1, CITED-1, HBME1 and cytokeratin-19 immunohistochemistry is useful for the differential diagnosis of thyroid tumors. Mod Pathol 2005; 18: 48e57. Rosai J. The encapsulated follicular variant of papillary carcinoma: back to the drawing board. Endocr Pathol 2010; 21: 7e11.
Answer 2 (a) The cells are cuboidal but a little taller than normal thyroid epithelium. The nuclei are oval, grooved, partially overlapping, and have some central clearing.
DIAGNOSTIC HISTOPATHOLOGY 17:11
508
Ó 2011 Elsevier Ltd. All rights reserved.
SELF-ASSESSMENT
comprising these cells were of unpredictable behaviour and € rthle cell “tumours”. It is now known should be termed Hu that the defining criteria for malignancy are exactly the same as for follicular neoplasms in general. € rthle cell tumours are more likely than ordinary Hu follicular neoplasms to show invasion and thorough € rthle cell neoplasms is therefore important. sampling of Hu They are also more likely to show tumour necrosis. Any cystic necrotic thyroid tumour should be carefully searched € rthle cell elements. for Hu They are generally considered to be a little more aggressive than standard follicular carcinoma and, unlike it, may metastasize to lymph nodes. Those that metastasize to lymph nodes may well be in effect papillary carcinomas, not recognized as such because the nuclear features are not well € rthle cell developed. The somewhat poorer prognosis of Hu carcinomas may be because their uptake of radio-iodine is often low. The finding of apparent follicular carcinoma in a lymph node should always prompt consideration that it may be 1) follicular variant papillary carcinoma or 2) € rthle cell carcinoma. Hu € rthle cell tumours needs to Immunohistochemistry of Hu be interpreted with caution, due to non-specific uptake, particularly when the avidinebiotin technique is used.
Sobin LH, Gospodarowicz MK, Wittekind C. UICC TNM classification of malignant tumours, 7th edn. Wiley-Blackwell, 2009. Stephenson TJ. Papillary carcinoma of the thyroid: a tumour still with no benign neoplastic counterpart. Histopathology 2001; 39: 536e38. Stephenson TJ. Prognostic and predictive factors in endocrine neoplasia. Histopathology 2006; 48: 629e43. Stephenson TJ, Johnson SJ. Dataset for thyroid cancer histopathology reports. London: RCPath, 2010.
Answer 3 (a) The significance of the Thy3f category is that a follicular neoplasm cannot be excluded. (b) The limitations of a Thy3f cytological diagnosis are that it is not possible to predict where the neoplasm will be benign or malignant. This is because cellular follicular nodules in multinodular goitre, follicular adenomas and follicular carcinomas may all give the same appearance of a population of follicular epithelial cells not accompanied by other features that point towards a benign diagnosis. (c) There are no further cytological investigations that can be done (although it is hoped that 1 day molecular biology, including proteomics, may assist the differential diagnosis) and investigation of the nodule usually requires histology of the nodule, excised by hemithyroidectomy. This is because the diagnosis of follicular carcinoma, including its oncocytic variant, rests on architectural features such as capsular and/or vascular invasion. (d) Figure 9 shows basically solid/follicular architecture, € rthle but nearly all the cells (by definition >80%) are Hu cells, equipped with granular eosinophilic cytoplasm and large nuclei with large eosinophilic central nucleoli, € rthle cell neoplasm. The apparent nuclear signifying a Hu pleomorphism and enlargement is common for € rthle cell neoplasm and does not have any implia Hu cation of whether it is malignant or not. Figure 10 shows vascular invasion within the capsule while Figure 11 shows full thickness capsular transgression by tumour, € rthle cell carcinoma. Finally, indicating that this is Hu Figure 12 shows widespread invasion of the original thyroid capsule with extension of the cancer into perithyroidal soft tissues indicating a pT3 tumour at least according to TNM version 7. The carcinoma may be incompletely excised, R1 resection, at this point.
FURTHER READING Asa SL. My approach to oncocytic tumours of the thyroid. J Clin Pathol 2004; 57: 225e32. Cross P, Chandra A, Giles T, et al. Guidance on the reporting of thyroid cytology specimens. London: RCPath, 2009. Guidelines for the management of thyroid cancer, 2nd edn. British Thyroid Association and Royal College of Physicians, 2007. Montone KT, Balock ZW, LiVolsi VA. The thyroid Hurthle (oncocytic) cell and its associated pathologic conditions: a surgical pathology and cytopathology review. Arch Pathol Lab Med 2008; 132: 1241e50. Stephenson TJ. Pathological spectrum of thyroid disease. Chapter 2. In: Arora A, Tolley N, Tuttle RM, eds. Practical manual of thyroid and parathyroid disease. Oxford: Blackwell Publishing, 2010: 14e24. Tallini G, Carcangiu ML, Rosai J. Oncocytic neoplasms of the thyroid gland (Review). Acta Path Jap 1992; 42: 305e15. Thompson LDR, ed. Endocrine pathology. Philadelphia: Elsevier, 2006: 351e57. €rthle Vodanovic S, Crepinko I, Smoje J. Morphologic diagnosis of Hu cell tumors of the thyroid gland. Acta Cytol 1993; 37: 317e22.
Discussion € rthle cells have voluminous eosinophilic cytoplasm rich Hu in mitochondria, as evidenced by special stains and electron microscopy. It was once thought that thyroid neoplasms
DIAGNOSTIC HISTOPATHOLOGY 17:11
509
Ó 2011 Elsevier Ltd. All rights reserved.