Symposium on Endocrine Pathology.
London. November 1997.
Slide Seminar Histories and answers
Contents
History: A 52 year old woman with a 5.5cm mass in one thyroid lobe. FNA twice had been negative.
Laser copy photograph sheets of original transparencies circulated (for cases 1&2).
Histology: both FNAs were interpreted as negative for malignancy but the lesion grew and was excised. The tumour was grossly encapsulated and composed of several areas. The most prominent was of a papillary growth pattern with true fibrovascular cores lined by the malignant epithelial cells. In other areas the tumour was more solid. In all areas the lesion was quite vascular and especially in the solid areas there were a few foci of pink homogenous material in the stroma. On special stains these were amyloid. The differential diagnosis was between papillary variant of medullary carcinoma, a papillary carcinoma of thyroid with solid areas, or a mixed medullary and papillary carcinoma of the thyroid.
Immunocytochemistry showed the tumour was negative for thyroglobulin ( with only rare, trapped follicles at the periphery staining positive) Tumour cells were strongly and diffusely positive for Calcitonin , CEA and less, but definitely positive for chromogranin.
There was no evidence for a mixed parafollicular type differentiation in this tumour.
Diagnosis: Medullary thyroid carcinoma - papillary variant
References:
Albores-Saavedra, J., et al: Medullary carcinoma. Sem Diag Pathol.1985;2:137-150
Brown, R. S. et al: The syndrome of multiple mucosal neuromas and medullary thyroid carcinoma in
Childhood. J Pediatr.1975; 86: 77-83.
Carney, J A et al: Multiple endocrine neoplasia, type 2b. Pathobiol. Annu.1978;8:105-153.
DeLellis, R. A. et al: C Cell hyperplasia: an ultrastructural analysis. Lab. Invest.1977;36:237-248.
Fernandes, B F et al: Mucus producing medullary cell carcinoma of the thyroid gland. Am J Clin Pathol.1982;78:536-540.
Geddle, W R e al: Medullary carcinoma of the thyroid in fine needle aspiration biopsies. Am J Clin Pathol.1984; 82: 552-558.
Harach, H R and Bergholm, U: Medullary (C Cell) carcinoma of the thyroid with features of follicular oxyphilic tumours. Histopathology.1988;13: 645-658.
Harach, H R and Williams, E D: Glandular (tubular and follicular) variants of medullary carcinoma of the thyroid. Histopathology.1983; 7: 83-97.
Kakudo, K et al: Medullary carcinoma of the thyroid: Giant cell type. Arch Pathol Lab Med.1978;102: 445-447. Kadudo, K et al: C cell carcinoma of the thyroid: papillary type. Acta Pathol Jpn.1979;29:653-659.
Kimura, N et al: Melanin producing medullary thyroid carcinoma with glandular differentiation. Acta Cytol.1989;33: 61-66.
Landon, G and Ordonez, N G: Clear cell variant of medullary carcinoma of the thyroid. Hum Pathol.1985;16: 844-847.
Marcus, J et al: Melanin production in a medullary thyroid carcinoma. Cancer.1982;49:2518-2526.
Posen, J A et al: Melanin-producing medullary carcinoma of the thyroid gland. S Afr Med J.1984; 65: 57- 59.
Saad, M F et al: The prognostic value of calcitoin immunostaining in medullary carcinoma of the thyroid. J Clin Endocrinol Metab.1984; 59: 850-858.
Saad, M F et al: Medullary carcinoma of the thyroid. A study of the clinical features and prognostic factors in 161 patients. Medicine.1984;63:319-342.
Zaalari, G S et al: Mucin production in medullary carcinoma of the thyroid. Arch Pathol Lab Med 1983;107:70-74.
Gagel, R F et al: Medullary thyroid carcinoma. Recent progress. J Clin Endocrinol. Metab. 1993;76: 809-815.
Hofstra, R M W et al: A mutation of RET protooncogene associated with MEN2b and sporadic Medullary carcinoma. Nature.1994; 367:375-376.
Quadro, L et al: Frequent RET protooncogene mutations in multiple endocrine neoplasia type 2A. J Clin Endocrinol Metat..1994; 79: 590-594.
Papotti, M et al: The pathology of medullary carcinoma of the thyroid: review of the literature and personal experience in 62 cases. Endocrine Pathol.1996; 7:1-20.
Komminth, P, Kunz, E K, Matias-Giui, X, et al: Analysis of ret protooncogene point mutations allows for the discrimination of sporadic and inherited medullary thyroid carcinoma. Cancer.1995;76:479-489.
Dominquez-Malagon, H et al: Oxyphil and squamous variants of medullary thyroid carcinoma. Cancer.1989;63:1183-1186.
Huss, L J et al: Medullary carcioma of the thyroid gland: An encapsulated variant resembling the Hyalinizing trabecular (paraganglioma-like) adenoma of the thyroid. Mod Pathol.1990;3: 581-585.
Histology: The FNA showed a cellular smear of follicular cells, colloid and nuclear features included; enlargement, oval nuclei, nuclear grooves and focally prominent intranuclear inclusions. The FNA diagnosis was suspected follicular variant of papillary carcinoma. The tumour in the lobectomy specimen was of a follicular pattern with appropriate nuclear features of a papillary carcinoma. However there were foci within and outside the tumour nodule of a poorly differentiated epithelial malignancy. These areas had cells with relatively large nuclei and deeply basophilic cytoplasm. In some areas this tumour surrounded follicles and the small microscopic foci of this highly malignant appearing tumour involved the stroma predominantly
Differential diagnosis. De-differentiated area of follicular variant of papillary carcinoma, a mixed medullary and papillary carcinoma, or that the highly malignant-looking component was metastatic.
Immunocytochemistry: the obvious follicular variant papillary carcinoma was positive for thyroglobulin. Both this tumour and the more malignant areas were negative for calcitonin. The more malignant areas were positive for NSE, synaptophysin and chromogranin focally; thyroglobulin was negative.
Conclusion: metastatic carcinoma to follicular variant of papillary carcinoma
Follow up: 5 months earlier the patient had a diagnosis of neuroendocrine carcinoma of the bronchus made on bronchial washings and brushings. She had received radiotherapy and chemotherapy with shrinkage of the pulmonary mass before the thyroid nodule was investigated. Comparison of the bronchial specimens and the poorly differentiated tumour of the thyroid showed morphological similarity and the conclusion was of metastatic neuroendocrine carcinoma to the thyroid papillary carcinoma.
Diagnosis: Metastatic neuroendocrine carcinoma (from lung) to follicular variant of papillary carcinoma of the thyroid
References:
Czech JM, Lichtor TR et.al. Neoplasms metastatic to the thyroid gland. Surg Gynecol.Obstet 1982;155:503-05
Shima H, Mori H et.a;. A case of renal cell carcinoma solitarily metastasising to thyroid 20 years after resection of primary tumour. Pathol. Res Pract 1985;179:666-70
Tibaldi JM et.al. Thyroiditis mimicked by metastatic carcinoma to the thyroid. Mayo Clin Proc. 1986';61:399-400
Ivy KH. Carcinoma metastatic to the thyroid Mayo Clin Proc. 1984:59:856-59
Martius- Giu X, Guette J et.al. Metastatic neuroendocrine tumours to the thyroid gland mimicking medullary carcinoma. Am J Surg Pathol 1997;21:754-62
Histology: This benign tumour is composed of relatively large chromophobe cells with large nuclei. It is hormonally functionless as demonstrated by immunocytochemistry, despite the intense metabolic activity evident in the profuse round mitochondria seen in the electron micrographs.
Oncocytomas of the anterior pituitary are not uncommon, accounting for 10% of pituitary tumours in some neurological series.
Diagnosis: Pituitary oncocytoma
References:
Kovacs K, Horvath A. Tumours of the pituitary gland. In: Atlas of tumour pathology, 2nd series, fasicle 21, Washington DC: AFIP 1986:1-264.
Kontogeorgos G, Kovacs K, Horvath A, Scheithauer BW. Null cell adenomas, oncocytomas and gonadotroph adenomas of the human pituitary: an immunocytochemical and ultrstructural analysis of 300 cases. Endocrinol Pathol 1993; 4:20-27
Histology: A well circumscribed parathyroid tumour composed of chief cells arranged in a solid pattern and showing an increased mitotic count. A t one edge there is a rim of normal parathyroid tissue merging with the more cellular hyperplastic lobular component. A fragment of thymic tissue is also present. The left upper parathyroid (slides not submitted) was histologically normal. ( The liver mass was diagnosed as focal nodular hyperplasia).
Diagnosis: Parathyroid adenoma
Histology: typical carcinoid with immunocytochemistry positive for Synaptophysin, Chromogranin and N.CAM
Diagnosis: Carcinoid tumour of bronchus
Histology: The slide shows fragments of a multinodular goitre. There are perivascular and interstitial deposits of amyloid. The Congo red stain is positive after Potassium Permanganate treatment. The follicular cells in the nodule stain positively for Thyroglobulin and negatively for Calcitonin and besides the amyloid deposits are also noticed outside the normal parenchyma. This is AL amyloid. The mediastinal nodes were also extensively infiltrated by amyloid.
The patient was known to have an IgG-lamda monoclonal gammopathy. The plasma cells in the marrow were increased to 10% and showed the same monoclonal profile. No lytic bone lesions or Bence-Jones protein were present. Therefore despite the extensive amyloid (lymph nodes, thyroid and subcutaneous vessels) the patient cannot be considered to have multiple myeloma as the criteria of Durie and Salmon are not fulfilled. It is well recorded that a proportion of patients with monoconal gammopathy of uncertain significance go on the develop multiple myeloma.
Diagnosis: Systemic AL- amyloidosis with deposits in a retrosternal goitre (patient known to have monoclonal gammopathy / plasma cell dyscrasia).
References:
Grogan TM and Spicer CM. The B cell immunoproliferative disorders, including multiple myeloma and amyloidosis. In: Knowles DN ed. Neoplastic Haematopathology. Baltimore. Willliams & Wilkins 1992;1235-65
LiVolsi VA. Amyloid in the thyroid. In: Surgical pathology of the Thyroid. Major problems in pathology, Vol 22. Bennington JL ed. Philadelphia WB Saunders. 1990; 111-112.
Tan SY Pepys MB. Amyloidosis. Histopathology.1994;24:403-14
Slide submitted from pancreas (autopsy).
Discussion: At autopsy more than 100 pancreatic neuroendocrine tumours were found, all less than 5mm diameter. Most tumours contained pancreatic polypeptide and/or glucagon. Insulin and somatostatin containing tumours were rare. None of the pancreatic tumours contained gastrin. Other autopsy findings included: one small 3mm duodenal gastrinoma, two lymph node metastases of gastrinoma and a TSH containing pituitary tumour. The pancreatic tumours in patients with MEN1 and ZES are almost never gastrinomas.
Diagnosis: Pancreatic microadenomas in a patient with MEN type I and Zollinger-Ellison syndrome.
References:
Pipeleers-Marichal M. Somers G, Willems G et.al. Gastrinomas in the duodenums of patients with multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome. NEJM 1990;322:723-27.
Donow C, Pipeleers-Marichal M, Schroder S. et.al. Surgical pathology of gastrinoma. Site, size multicentricity, association with MEN type 1 and malignancy. Cancer 1991;68:1329-34.
Pipeleers-Marichal M, Donow C, Heitz PU, Kloppel G. Pathological aspects of gastrinomas in patients with ZE syndrome with and without MEN type 1. World Journal of surgery 1993.17:481-88
*Please note correction to original details; measurements should be mm.
Histology: The tumour was lobulated with a soft yellow cut surface with some areas of haemorrhage. The residual adrenal gland was present at one edge.
The tumour was composed of sheets of eosinophilic compact cells, with focal areas of lipid laden cells (<25% of the total). There was moderate nuclear pleomorphism. Twenty three mitoses were present in 50HPF(x40), with occasional atypical mitoses. There was evidence of sinusoidal invasion but no venous or capsular invasion. There was confluent necrosis. Diagnosis of adrenocortical carcinoma was made. The adjacent adrenal cortex was atrophic comprising only lipid laden cells. This is consistent with autonomous secretion of cortisol by the tumour.
Comment: The diagnosis was made here using the system of Weiss. Two other protocols which can be used are those of Hough and Van Slooten. However, these are more difficult to apply because they involve assigning numerical values to a variety of features, The patient is likely to have a relatively poor prognosis because of the high mitotic rate. Presumably the high level of proliferation accounts for both the rapid increase in size and the development of clinical features of Cushing's syndrome in the preoperative period.
Incidental adrenocortical nodules are not infrequently found at autopsy and with scanning a proportion are identified in life during investigation for other conditions. The prevalence is form 0.06% at age 0-9years rising to 6.94 % at 75 years. The differential diagnosis of such nodules is: Adrenocortical nodule - adenoma or carcinoma; phaeochromocytoma; Myelolipoma; metastatic tumour.
On the basis of incidence only 0.06% of these should be carcinomas although in reported series they account for 0.25% which may be due to their larger size and greater recognition. At present it is unclear how such lesions should be treated. If biochemical tests show significant hormone production they would usually be removed. Non functioning lesions the usual, rather arbitrary approach would be to remove it is >5cm on the basis that they are more likely to be malignant. Smaller lesions would be followed up with scans if 3.5cm and remove if enlarging and leave if very small.
FNA cytology is increasingly being used in assessment of individual nodules. Although this is of use in subdividing into the main differential diagnostic categories it is not useful in distinguishing benign from malignant potential in either adrenocortical tumours of Phaeochromocytomas.
Diagnosis: Adrenocortical carcinoma
References:
Weiss LM. Am J Surg Pathol. 1984;8:163-69
Hough AJ et al. Am J Clin Pathol. 1979;72:390-99
Van Slooten H et al. Cancer 1985;55:766-73
Kloos RT et al. Endocrine Reviews 1995;16:460-83
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