UK Endocrine Pathology Society Slide Circulation 16 – Discussion Document October 2007

Case 1 81 year old woman. Primary hyperparathyroidism.

This showed a parathyroid tumour with invasion into the capsule and extensive vascular invasion. There was also possible perineural invasion. The lesion was not excised.

This was simply a good example of parathyroid carcinoma. The discussion points were whether people normally count mitoses or a MIB-1 index or comment on whether they are present or absent. Most people do not.

Diagnosis: Parathyroid carcinoma.

Case 2 55 year old woman. No clinical details given. Right thyroid lobectomy. Additional clinical details at meeting – solitary nodule in right lobe thyroid.

Macro: A lobe of thyroid weighing 13 grams and measuring 40 x 25 x 15mm. Slicing showed a circumscribed nodule 15mm in diameter. This had an outer rim of yellow tissue and the contents were crumbly, possibly necrotic. At one end of the nodule the contents resembled old clotted blood. The remainder of the thyroid had a somewhat nodular appearance.

Micro: the major part of the nodule contained degenerate blood and necrotic epithelial cells with some calcified debris. Peripherally there was abundant fibrous tissue containing numerous macrophages and multi-nucleated giant cells. There was a rim of tumour tissue comprising oncocytic cells with an acinar and clefted appearance and in some places a pseudopapillary arrangement. There was some discussion as to the changes in the nuclei. Did they amount to optically clear nuclei or were they changes of degeneration in oncocytes? The general impression was that they represented the latter. No invasion was identified. The lesion had been diagnosed as an oncocytic nodule with no evidence of malignancy. The background thyroid was confirmed as showing nodular hyperplasia.

Obviously oncocytic tumours can undergo necrosis following FNA. However it was discovered after this excision that a previous FNA had been done but already showed numerous haemosiderin laden macrophages indicative of previous haemorrhage. It is likely, therefore, that the lesion had undergone haemorrhage and necrosis before the FNA.

Diagnosis: Oncocytic follicular nodule (adenoma) with degenerative change.

Case 3 50 year old man. Solitary thyroid nodule.

This was an encapsulated nodule which at its centre had a slightly trabecular appearance and early hyalinisation. The nuclei showed some vacuolation and inclusions with slight grooving but this was not marked throughout. There was no evidence of invasion. The differential diagnosis was between an encapsulated papillary carcinoma, possibly a follicular variant type; hyalinising trabecular tumour; and follicular adenoma. The tumour was positive for cytokeratin 19 and showed cytoplasmic MIB-1 staining, a characteristic feature of hyalinising trabecular tumour. The nature of these tumours is unclear. There is evidence from molecular genetic analysis that some of them show the genetic abnormalities as papillary carcinoma. However, not all do. Most of them behave in a benign fashion but occasional malignant tumours have been reported.

Diagnosis: Hyalinising trabecular tumour

Case 4 30 year old woman. Nodule in left lobe of thyroid – cyst. Incidental 7mm tan coloured nodule in contralateral lobe.

This was an encapsulated nodule without capsular or vascular invasion. The trabeculae of follicular cells were separated by hyaline material. There was some partial nuclear clearing. Immunocytochemistry for CK19 was strongly positive and MIB-1 showed cytoplasmic staining. This was also therefore diagnosed as a hyalinising trabecular tumour. However there was some discussion and most people would not have diagnosed this case as such. The relevance of the cytoplasmic MIB – 1 staining was debated.

Diagnosis: ? hyalinising trabecular tumour ? follicular adenoma

Comment on cases 3 and 4.

I have found a recent article (reference below) that tends to indicate that the expected pattern of cell membrane and peripheral cytoplasmic staining with MIB-1 is seen only with that antibody and not with other Ki-67 antibodies [1]. The paper also indicated that it is seen only if the immunostaining is carried out at room temperature. Automated immunostainers that operate at 37 degrees do not produce this membrane localisation. I find this interesting because I have certainly had cases that I would have diagnosed as HTT that did not show cytoplasmic/membrane staining. We use a Techmate. I have also given a reference below for a recent update on this entity [2].

Case 5 40 year old man. 21 hydroxylase deficiency. Previous bilateral adrenalectomies – myelolipoma. Recurrent right mass.

This specimen again showed changes of myelolipoma with residual adrenal tissue also present. The pathogenesis of adrenal myelolipomas is unclear. However they have been reported in a number of patients with congenital enzyme deficiencies [3- 5]. A recent study has suggested that they are neoplastic as the fat and haemopoietic cells are clonal [6].

Diagnosis: Adrenal myelolipoma

Case 6 78 year old man. Nodule in right lobe of thyroid – follicular adenoma. Second nodule.

This lobectomy specimen contained two nodules. The larger was a follicular adenoma. The smaller nodule was encapsulated and had what was probably follicular morphology. The nuclei were displaced peripherally by globules of a clear substance which stained positively for thyroglobulin. The lesion is a signet ring cell follicular adenoma [7-10]. Some have suggested that these represent an arrest in folliculogenesis with entrapment of hormone in the cells. Some also contain mucin within the vacuoles.

Diagnosis: Signet ring cell follicular adenoma

Case 7 87 year old man. Mass overlying thyroid cartilage and thyroid isthmus.

There were two nodules within this specimen, both present within a thyroglossal duct tract [11-14]. The superior nodule was follicular.

The tumour circulated is a heterogeneous tumour showing a range of histological appearances. In areas, it shows obvious thyroid differentiation with cells arranged in cribriform, solid and follicular patterns with focal true papillae formation. In these areas, the nuclei have delicate chromatin and there are occasional nuclear grooves. The appearances in these areas are consistent with papillary thyroid carcinoma. Elsewhere, it is more more poorly differentiated component with areas showing an insular architecture . Here the nuclei of the cells are larger, although many still do show the features of papillary carcinoma. In several foci, however, the cells are much more pleomorphic with nuclei which have lost the features of papillary carcinoma. These areas are associated with prominent mitotic figures and widespread tumour cell necrosis. Scattered cells showing a rhabdoid morphology are also noted. Vascular invasion is present.

The well differentiated areas express TTF1 and thyroglobulin, but expression is lost in the poorly differentiated areas. Immunohistochemistry for CK19 and galectin-3 is positive in the majority of the tumour cells, but chromogranin A and calcitonin is negative.

Diagnosis: Thyroglossal duct tumour - poorly differentiated thyroid carcinoma, probably arising in a papillary carcinoma

Case 8 41 year old woman. Mass in right lobe of thyroid.

This has a mixed architectural pattern with some follicular areas, trabecular areas and foci of abortive papillary change with a few true papillae. In some of these areas the appearances are reminiscent of hyalinising trabecular tumour. In the follicular areas the nuclei are small and round but elsewhere, there are areas where the cells show nuclear clearing although there are no grooves or inclusions. In places there appears to be capsular invasion with nodules of tumour lying outwith the capsule of the main lesion.

In light of the mixture of features (after discussion) this tumour was classified as carcinoma of follicular cell origin, not otherwise specified [15].

Diagnosis: Carcinoma of follicular cell origin, NOS.

References

1. Leonardo E, Volante M, Barbareschi M, Cavazza A, Paolo Dei Tos A, Bussolati G, et al. Cell membrane reactivity of MIB-1 antibody to Ki67 in human tumors: fact or artifact? Appl Immunohistochem Mol Morphol 2007;15(2):220-3. 2. Nose V, Volante M, Papotti M. Hyalinizing Trabecular Tumor of the Thyroid: An Update. Endocr Pathol 2007. 3. Sakaki M, Izaki H, Fukumori T, Taue R, Kishimoto T, Kanayama HO. Bilateral adrenal myelolipoma associated with adrenogenital syndrome. Int J Urol 2006;13(6):801-2. 4. Nagai T, Imamura M, Honma M, Murakami M, Mori M. 17alpha-hydroxylase deficiency accompanied by adrenal myelolipoma. Intern Med 2001;40(9):920-3. 5. Murakami C, Ishibashi M, Kondo M, Ohshiro S, Fujita M, Sato S, et al. Adrenal myelolipoma associated with congenital adrenal 21-hydroxylase deficiency. Intern Med 1992;31(6):803-6. 6. Bishop E, Eble JN, Cheng L, Wang M, Chase DR, Orazi A, et al. Adrenal myelolipomas show nonrandom X-chromosome inactivation in hematopoietic elements and fat: support for a clonal origin of myelolipomas. Am J Surg Pathol 2006;30(7):838-43. 7. Yoshida J, Tanimura A, Yamashita H, Matsuo K. Signet ring cell adenoma of the thyroid with mucin predominance. Thyroid 1999;9(4):401-4. 8. Markaki S, Prevedorou D, Kyratsis G, Bouropoulou V. Follicular thyroid adenoma: signet ring cell variant. Arch Anat Cytol Pathol 1990;38(3):114-6. 9. Gherardi G. Signet ring cell 'mucinous' thyroid adenoma: a follicle cell tumour with abnormal accumulation of thyroglobulin and a peculiar histochemical profile. Histopathology 1987;11(3):317-26. 10. Schroder S, Bocker W. Signet-ring-cell thyroid tumors. Follicle cell tumors with arrest of folliculogenesis. Am J Surg Pathol 1985;9(9):619-29. 11. Cignarelli M, Ambrosi A, Marino A, Lamacchia O, Cincione R, Neri V. Three cases of papillary carcinoma and three of adenoma in thyroglossal duct cysts: clinical-diagnostic comparison with benign thyroglossal duct cysts. J Endocrinol Invest 2002;25(11):947-54. 12. LiVolsi VA, Perzin KH, Savetsky L. Carcinoma arising in median ectopic thyroid (including thyroglossal duct tissue). Cancer 1974;34(4):1303-15. 13. Astl J, Duskova J, Kraus J, Vlcek P, Kodet R, Lastuvka P, et al. Coincidence of thyroid tumor and thyroglossal duct remnants. Review of the literature and presentation of three cases. Tumori 2003;89(3):314-20. 14. Falvo L, Giacomelli L, Vanni B, Marzollo A, Guerriero G, De Antoni E. Papillary thyroid carcinoma in thyroglossal duct cyst: case reports and literature review. Int Surg 2006;91(3):141-6. 15. Williams ED. Guest Editorial: Two Proposals Regarding the Terminology of Thyroid Tumors. Int J Surg Pathol 2000;8(3):181-183.