Proposal for an extended pTNM classification of thyroid carcinoma : Commentary on deficits of the 8th edition of the TNM classification.

In the 8th edition of the TNM classification of thyroid carcinomas, which was introduced in 2017, carcinomas with minimal extrathyroidal extension are no longer mentioned, which might cause problems. These tumors were explicitly categorized in previous TNM classifications (5-7th editions). Studies on the prognostic relevance of minimal extrathyroidal extension have shown conflicting results. Moreover, the vast majority of these studies retrospectively analyzed only subgroups of thyroid carcinomas (e.g. differentiated thyroid carcinoma, papillary thyroid carcinoma). The proposed subcategorization of the current TNM classification (8th edition) ensures the continuity of the parameter minimal extrathyroidal extension within the TNM categorization of thyroid carcinomas and also offers the possibility to prospectively analyze in a standardized manner the potential biological relevance of minimal extrathyroidal extension in relation to tumor categories (T/pT category).

[Proposal for an extended pTNM classification of thyroid carcinoma : Commentary on deficits of the 8th edition of the TNM classification (German version)]. / Vorschlag zu einer erweiterten pTNM-Klassifikation der Schilddrüsenkarzinome : Kommentar zu Defiziten der 8. Auflage der TNM-Klassifikation.

In the 8th edition of the TNM classification of thyroid carcinomas, which was introduced in 2017, carcinomas with minimal extrathyroidal extension are no longer mentioned, which might cause problems. These tumors were explicitly categorized in previous TNM classifications (5-7th editions). Studies on the prognostic relevance of minimal extrathyroidal extension have shown conflicting results. Moreover, the vast majority of these studies retrospectively analyzed only subgroups of thyroid carcinomas (e.g. differentiated thyroid carcinoma, papillary thyroid carcinoma). The proposed subcategorization of the current TNM classification (8th edition) ensures the continuity of the parameter minimal extrathyroidal extension within the TNM categorization of thyroid carcinomas and also offers the possibility to prospectively analyze in a standardized manner the potential biological relevance of minimal extrathyroidal extension in relation to tumor categories (T/pT category).

[Lysosomal acid lipase deficiency (LAL-D) : Diagnostic and therapeutic options in an underdiagnosed disease]. / Mangel an lysosomaler saurer Lipase (LAL-D) : Diagnostik und aktuelle Therapie einer unterdiagnostizierten Erkrankung.

BACKGROUND AND CLINICAL SETTING: Lysosomal acid lipase deficiency is an autosomal recessive storage disease caused by mutations in the LIPA gene. The accumulation of cholesteryl esters and triglycerides in hepatocytes lead to hepatomegaly with progressive fibrosis and liver cirrhosis. Characteristically, patients have a hepatomegaly combined with high serum levels of cholesterol, LDL-cholesterol and in some cases triglyceride, whereas HDL-cholesterol is decreased. Histologically, hepatocytes show a microvesicular steatosis with typically ballooned Kupffer cells. Even though histological morphology is typical, it is not characteristic. Therefore LAL-D is supposed to be an underdiagnosed disease with a high number of unreported cases misdiagnosed as uncharacteristic fatty liver disease (NASH, NAFLD, cryptogenic liver cirrhosis). Further, there is overlap with other storage diseases, complicating a correct diagnosis. THERAPY: Until recently, different therapeutic options could not prevent development of liver cirrhosis. Patients with Wolman's disease have an especially rapid progression and die within the first six months of life. With the recent development of a new enzyme replacement therapy with sebelipase alfa (Kanuma ®), new therapeutic options with significant improvement of dyslipidemia and reduction of transaminases have become reality. Positive clinical results seem to have the potential to significantly raise life expectancy. CONCLUSION: These new therapeutic options warrant an increase in awareness of LAL-D by clinicians and pathologists. Correct diagnosis of LAL-D is important for effective therapy and long-term survival.

[Definition of R1 resection in thyroid carcinoma]. / Definition der R1-Resektion bei Schilddrüsenkarzinomen.

BACKGROUND: The residual tumor (R) classification describes the tumor status after therapy, which in patients with thyroid carcinomas is predominantly after surgical treatment. The aim of the R classification is to indicate the success of (surgical) therapy, which can influence further therapeutic procedures and allow relevant prognostic statements. OBJECTIVE: Definition of R1 resection as well as minimally invasive extrathyroidal growth of thyroid carcinomas as the latter is a common prerequisite for R1 resected thyroid carcinoma. RESULTS: Presentation of the pathological work-up and histopathological assessment. Proposal to supplement and extend the recently introduced 8th edition of the TNM classification in order to systematically classify minimally invasive extrathyroidal carcinomas. CONCLUSION: The presented definitions (e.g. R1, minimally invasive extrathyroidal invasion) in combination with the proposed extension of the TNM classification permit the prospective scientific assessment of the biological relevance of these two parameters.

[Inflammation of the parathyroid glands]. / Entzündungen der Nebenschilddrüsen.

Inflammation of the parathyroid glands is rare when compared to other endocrine organs. This leads to the use of descriptive terms as well as the lack of a generally accepted classification for inflammatory disorders of the parathyroid glands. This review article proposes that parathyroid inflammation be subdivided morphologically into (a) non-specific lymphocytic infiltration, which is more an expression of damage to small vessels, due to e. g. severe systemic inflammation or myocardial infarction, (b) autoimmunogenic lymphocytic parathyroiditis, (c) nonimmunogenic inflammation caused by granulomatous diseases or infections and (d) invasive sclerosing (peri) parathyroiditis. As only parathyroid glands removed due to hyperparathyroidism and normal parathyroid glands incidentally removed during thyroid surgery are seen almost exclusively in routine histopathology, virtually no information about the morphological correlate of hypoparathyroidism is available.

[Inflammatory diseases of the thyroid gland]. / Entzündungen der Schilddrüse.

This review article deals with the classification, clinical features and morphology of thyroiditis. These inflammatory diseases account for approximately 20 % of all thyroid diseases. The vast majority of cases of thyroiditis are of immunogenic origin while non-immunogenic thyroiditis (caused by pathogens or iatrogenic) is a rarity.

[Clinical importance of thyroid gland cytology]. / Klinische Bedeutung der Schilddrüsenzytologie.

The cytological evaluation of fine needle biopsies (FNB) of the thyroid gland crucially depends on a close cooperation between clinicians and cytopathologists. Scintigraphy, sonography as well as clinical data and patient history are necessary for a correct interpretation of the indications for FNB; moreover, these data are of outstanding importance for cytopathologists for the correct interpretation of the cytomorphological findings. This overview describes the present standards in the acquisition, technical workup and cytopathological interpretation of thyroid gland tissue obtained by FNB, particularly focusing on the rapidly growing relevance of additional molecular pathological investigations to increase the diagnostic accuracy of thyroid FNB.

[Intraoperative frozen sections of the thyroid gland]. / Intraoperativer Gefrierschnitt der Schilddrüse.

The goal of evaluation of intraoperative frozen sections of the thyroid gland is to achieve a definitive diagnosis which determines the subsequent surgical management as fast as possible; however, due to the specific methodological situation of thyroid frozen sections evaluation a conclusive diagnosis can be made in only some of the cases. If no conclusive histological diagnosis is possible during the operation, subsequent privileged processing of the specimen allows a final diagnosis at the latest within 48 h in almost all remaining cases. Applying this strategy, both pathologists and surgeons require a high level of communication and knowledge regarding the specific diagnostic and therapeutic peculiarities of thyroid malignancies because different surgical strategies must be employed depending on the histological tumor subtype.

[Thyroid C cells and their pathology: Part 1: normal C cells, - C cell hyperplasia, - precursor of familial medullary thyroid carcinoma]. / Die C-Zellen der Schilddrüse und ihre Pathologie : Teil 1: Normale C-Zellen - Hyperplasie der C-Zellen - Präkanzerose des familiären medullären Karzinoms.

The C cells (parafollicular) of the human thyroid gland are predominantly located within the thyroid follicles, are of neuroendocrine origin and produce and secrete the peptide hormone calcitonin. Calcitonin is clinically utilized as a screening marker to detect occult medullary thyroid carcinoma (MTC) as well as in the follow-up of patients with MTC. An increase in the number of C cells is designated as C cell hyperplasia (CCH). Neoplastic CCH is caused by an autosomal dominant inherited mutation of the RET protooncogene, which develops into invasive familial MTC in the setting of multiple endocrine neoplasia (MEN) type 2 depending on the location of the mutation in the RET gene with a high variation in latency. According to the current state of knowledge CCH without a germline mutation in the RET protooncogene, designated as non-MEN2-associated CCH, seems to be unrelated to the development of sporadic MTC.

[Thyroid C cells and their pathology: Part 2: Medullary thyroid carcinoma]. / Die C-Zellen der Schilddrüse und ihre Pathologie : Teil 2: Medulläres Karzinom der Schilddrüse.

All tumours with C cell differentiation are designated as medullary carcinomas (MTC). MTC occur sporadically (75-80%) or hereditary (20-25%), the latter being part of the multiple endocrine neoplasia type 2. Familial MTC, which is commonly preceded by "neoplastic" C cell hyperplasia, is caused by autosomal-dominant inherited germ line mutation of the RET-protooncogene; dependent on the codon affected by the mutation, patients show substantially different clinical courses. Due to its morphological heterogeneity, the immunohistochemical demonstration of calcitonin is mandatory for the diagnosis of MTC. For early diagnosis of MTC calcitonin screening has been introduced in Germany and Austria approx. 10 years ago in patients with thyroid nodules; however, an increased calcitonin serum level may also be caused by "non-MEN2-associated" C cell, which is not regarded as a precursor of sporadic MTC. Very rarely tumours may show a mixed C cell-follicular cell differentiation.