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Poorly Differentiated Thyroid Carcinoma Pathology Outlines

Oncocytic Subtypedoes It Matter

Poorly Differentiated Carcinoma of the Thyroid with Dr. Margaret Brandwein

Based on their neoplastic tumor of origin, PDTCs can be subdivided into papillary type, follicular type, and not otherwise specified . However, this subdivision does not have any clinical or prognostic consequences .

Owing to a lack of data, oncocytic carcinomas were excluded in the Turin proposal and therefore it was initially unknown whether these criteria were also applicable to oncocytic lesions. We reported that the Turin criteria can also be applied in this scenario . However, it should be emphasized that the presence of necrosis in these tumors should not be overestimated since oncocytic lesions in general are prone to spontaneous or FNA-initiated infarction and focal necrosis. Thus, one should carefully look for signs of previous FNA in a given case. And while the relapse-free survival is similar between PDTC and oncocytic PDTC, it is nevertheless very important to distinguish between PDTC and oncocytic PDTC, since oncocytic PDTC may have an even worse overall survival than conventional PDTC .

Poorly Differentiated Thyroid Carcinomas

Clinical Features and Pathogenesis

Poorly differentiated thyroid carcinomas include a heterogeneous group of neoplasms whose behavioral and histologic features are intermediate between well-differentiated and anaplastic thyroid carcinomas.341343 Synonyms include insular carcinoma. The frequency of this tumor type appears to differ in different geographic regions. In central Italy, the tumors account for approximately 4% of all thyroid carcinomas. It is much less common in the United States and most other countries.

There is a slight female predominance, and the median age at diagnosis is 55 years. Most patients present with a thyroid mass of variable duration. Analysis of several series of cases revealed regional metastases in 36% and distant metastases in 26% at presentation.283

Pathologic Features and Differential Diagnosis

Papillary thyroid carcinomas may also show high-grade features or act like a poorly differentiated thyroid carcinoma however, there is lack of a consensus for utilizing these additive terms in papillary thyroid carcinoma specifically. The pathology group at Memorial Sloan Kettering Cancer Center proposed a definition for poorly differentiated thyroid carcinoma that includes any follicular cell-derived tumors, including papillary morphology as tumors with > 5 mitoses/10 HPF and/or tumor necrosis.347

Treatment and Prognosis

Edmund S. Cibas, in, 2014

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Interpretation Of Immunoistochemical Stains

The immunohistochemical expression of IMP3 and the expression of p53 and HBME-1 were scored by considering both the intensity and the extent of the stain using a semi-quantitative scoring system. The criteria for intensity score were as follows: 0 for no staining 1+ for weak staining 2+ for moderate staining and 3+ for strong staining. The criteria for scoring the extent of the stain were as follows: 0 for no staining 1+ for staining < 25% of neoplastic cells 2+ for staining 2550% of neoplastic cells and 3+ for staining > 50% of the neoplastic cells. The two scores were cumulated and a stain was considered positive with a combined immunohistochemical score higher than 2, whereas a final score of 2 or lower was considered negative.

Secondary Tumors / Metastases

Pathology Outlines

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  • Tumors arising in thyroid by direct extension from adjacent structures or by vascular spread from nonthyroidal sites
  • Despite being highly vascularized, the thyroid is a rare site for distant metastases
  • The frequency of metastasis in routine practice is < 0.2% of thyroid malignancies
  • Direct extension common from tumors of larynx, pharynx, trachea, esophagus and neck – usually are squamous cell carcinoma
  • FNA is useful for diagnosis of solitary metastases
  • More than 1400 cases have been published in series and individual case reports
  • Tumor to tumor metastasis localized within a primary thyroid neoplasm are very rare with 30+ cases reported
  • Thyroid is highly vascularized but secondary metastases to the gland are very uncommon
  • Secondary tumors arise from direction extension of head and neck squamous cell carcinoma and distant metastases from kidney, lung, GI and breast
  • Tumors preoperatively diagnosed by FNA, cytology, histopathology and immunophenotype are matched with a primary tumor
  • Lung cancer is the most common primary for thyroid metastasis in Asian series
  • Infradiaphragmatic primaries are more common than supradiaphragmatic
  • Renal cell carcinoma is the most common primary in clinical series, while lung cancer is the most common inautopsy studies
  • 67 year old man presented with a thyroid mass
  • Tumor to tumor metastases
  • Melanoma in OFA

    D.

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    Poorly Differentiated Thyroid Carcinoma

    Some carcinomas derived from follicular cells are not readily classified as one of the differentiated carcinomas nor as an undifferentiated carcinoma. They fall somewhere in between, based on an intermediate degree of nuclear and architectural atypia. These tumors are called poorly differentiated thyroid carcinomas and account for 4% to 7% of thyroid carcinomas.59,122,123 Nodal, pulmonary, and bone metastases are common at the time of diagnosis. Patients with a PDTC fare worse than those with one of the differentiated thyroid cancers, but better than those with an undifferentiated carcinoma.106 The 5-year survival rate is about 50%.

    The PDTCs are a heterogeneous group, with three principal histologic patterns: insular, trabecular, and solid. In the insular pattern, the malignant cells are arranged in well-defined nests surrounded by thin fibrovascular septae. Other PDTCs have a predominantly trabecular or solid growth pattern without nests. In all three patterns, some microfollicles can be seen. Tumor cells are generally small to intermediate in size and uniform, with some hyperchromasia, but pleomorphism is absent or only focal. Mitoses and necrosis are present. Nuclear features of papillary thyroid carcinoma are common, but some PDTCs more closely resemble follicular carcinoma or its oncocytic variant.106 They are immunoreactive for thyroglobulin, TTF-1, and PAX8.

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    Poorly Differentiated Thyroid Cancer

    PDTC, in comparison, usually has an intermediate level of IHC positivity for thyroid markers, falling somewhere between the strongly positive WDTC and weak ATC signals.

    Uniform cells arranged in microfollicles, no mitosis, necrosis

    Diagnosis is based on conventional nuclear features

    Presence of isolated cells suggests diagnosis of poorly differentiated thyroid carcinoma

    Often has increased mitotic activity and necrosis

    Microfollicles and colloid support diagnosis of PDTC

    Positive for calcitonin and neuroendocrine markers negative for thyroglobulin

    Aggressive tumor with rapid disease course

    Isolated cells with marked nuclear pleomorphism

    Cytomorphology Of Poorly Differentiated Thyroid Carcinoma

    67-Year-Old Woman With Differentiated Thyroid Cancer

    mitoses, necrosis

    The diagnosis of PDTC rests on histologic evaluation and cannot be made with certainty by FNA. Nevertheless, some general comments can be made. Cytologic preparations are usually highly cellular , with numerous isolated tumor cells as well as clusters of overlapping cells. Microfollicles are often present. In many cases the tumor cells are uniform in size and shape,122 but a greater degree of atypia is seen in some cases . Cytoplasm is poorly defined, and occasional cytoplasmic vacuoles are present. Intranuclear inclusions and nuclear grooves also may be seen.122,124 Colloid is scant.

    The possibility of PDTC can be supported by the immunocytochemical proliferation index. The Ki67/MIB1 index in well differentiated carcinomas is usually low , whereas the index in PDTC is in the range of 10% to 30%.59

    The differential diagnosis is broad in scope. The presence of intranuclear inclusions and grooves in many of these tumors suggests a papillary thyroid carcinoma, but the prominence of isolated cells is unusual and might suggest PDTC. Nuclear pleomorphism, if present, raises the possibility of an undifferentiated carcinoma. Most notably, PDTC has a striking resemblance to MTC, but microfollicles with colloid support the diagnosis of PDTC. Immunohistochemistry can be useful: PDTCs are thyroglobulin-positive and calcitonin-negative.

    LORETTA L.Y. TSE, JOHN K.C. CHAN, in, 2009

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    High Grade And Poorly Differentiated Carcinoma Of The Thyroid: The Last 20 Years Of Learning

    The Pathology department is a broad-based collection of anatomic pathologists , clinical pathologists and basic/ translational researchers . This monthly series of one-hour presentations by intramural and extramural presenters is designed to update our faculty with alternative sources of information and experience on controversial or newly emerging topics that are likely to change diagnostic pathology practices that cannot be gleaned from reading the literature or standard textbooks in pathology. There are many areas in pathology where a uniformly acceptable standard has not yet been established. Direct interaction with an expert can provide the pathologist with additional insights pertaining to these 3 branches of practice with the hope that much of the audience will gain new knowledge that meaningfully changes their practice.

    Key Words:

    Participants who engage in this educational intervention will be able to:

    • Describe the concept of aggressive thyroid cancer
    • Identify and distinguish “poorly-differentiated carcinoma” and “high grade carcinoma” of the thyroid
    • Discuss the prognostic implications of these tumors

    Papillary Thyroid Carcinoma Overview

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    • Papillary thyroid carcinoma is the most common type of thyroid carcinoma, defined by a set of distinctive nuclear features, including:
    • Change of nuclear size and shape: nuclear enlargement, elongation and overlapping
    • Chromatin characteristics: chromatin clearing, margination and glassy nuclei
    • Nuclear membrane irregularity: irregular nuclear contour, nuclear groove and nuclear pseudoinclusion
  • There are 15 variants of papillary thyroid carcinoma, including prototypic conventional / classic papillary thyroid carcinoma, as per the 2017 WHO classification , 4th Edition, 2017)
    • Diagnosis is based on nuclear features
    • Subtyping is based on a combination of architecture / pattern, cytologic features, size and encapsulation
    • BRAFV600E is the most frequent mutation, particularly in tall cell and classic variants
    • ICD10: C73 – malignant neoplasm of thyroid gland
    • ICD-0 : 8260/3 – papillary carcinoma of thyroid
    • Predominant form of thyroid carcinoma, accounting for 80 – 93% in contemporary series
    • There is a growing number of papillary thyroid carcinoma in the last 15 – 20 years due to increasing recognition of thyroid nodules on imaging , sometimes referred as thyroid cancer epidemics most of these tumors are of low risk
  • Occult tumors in 6% at autopsy , 46% multicentric, 14% with nodal metastases
  • Images hosted on other servers:

    TCGA

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    How Much Poorly Differentiated Is Needed

    It has long been known that there are PDTCs with a minor and even a major component of a well-differentiated thyroid carcinoma like PTC or FTC. Today, it is believed that most of them arise in a well-differentiated thyroid carcinoma, although a subset of these lesions apparently also arise de novo . About 80% of PDTC have a PD component of > 50%, and only 20% of PDTC have a minor PD component . However, it was unclear in the Turin proposal what percentage of poorly differentiated was needed in a tumor to allow for such a diagnosis andmore importantlyto affect patient prognosis moreover, the 2004 WHO classification did not offer a cut-off value . We showed that even a small PD component of 10% affects patient prognosis equally negative as a tumor that consists of 100% PD regarding relapse-free survival or overall survival . Our findings were recently confirmed by others and are now reflected in the current WHO classification . Therefore, a thorough histological work-up is highly recommended to ensure an adequate diagnosis is made.

    Fig. 3

    Clinical Features And Pathogenesis

    Anaplastic Thyroid Cancer Cytology

    Poorly differentiated thyroid carcinomas include a heterogeneous group of neoplasms whose behavioral and histologic features are intermediate between well-differentiated and undifferentiated thyroid carcinomas.267269 The best described tumor of this group is classified as insular carcinoma. The frequency of this tumor type appears to differ in different geographic regions. In central Italy, the tumors account for approxi mately 4% of all thyroid carcinomas. It is much less common in the United States and most other countries.

    There is a slight female predominance, and the median age at diagnosis is 55 years. Most patients present with a thyroid mass of variable duration. Analysis of several series of cases revealed regional metastases in 36% and distant metastases in 26% at presentation.219

    Zubair W. Baloch, Virginia A. LiVolsi, in, 2021

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    Who Classification

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    • Tumours of the thyroid gland ICD 0 codes
    • Follicular adenoma 8330/0
    • Other encapsulated follicular patterned thyroid tumours
    • Follicular tumours of uncertain malignant potential 8335/1
    • Well differentiated tumour of uncertain malignant potential8348/1
    • Noninvasive follicular thyroid neoplasm with papillary-like nuclear features 8349/1
  • Papillary thyroid carcinoma
  • Columnar cell variant of PTC8344/3
  • Oncocytic variant of PTC8342/3
  • Follicular thyroid carcinoma , NOS8330/3
  • FTC, minimally invasive8335/3
  • Poorly differentiated thyroid carcinoma 8337/3
  • Anaplastic thyroid carcinoma 8020/3
  • Mixed medullary and follicular thyroid carcinoma 8346/3
  • Mucoepidermoid carcinoma 8430/3
  • Sclerosing mucoepidermoid carcinoma with eosinophilia 8430/3
  • Mucinous carcinoma 8480/3
  • Spindle epithelial tumour with thymus-like differentiation 8588/3
  • Intrathyroid thymic carcinoma 8589/3
  • Paraganglioma and mesenchymal / stromal tumours
  • Paraganglioma 8693/3
  • Peripheral nerve sheath tumours
  • Schwannoma9560/0
  • Follicular dendritic cell sarcoma 9758/3
  • Primary thyroid lymphoma
  • 9080/3 Malignant teratoma9080/3
  • Secondary tumours
    • Tumours of the parathyroid glands ICD 0 codes
    • Parathyroid carcinoma 8140/3
    • Parathyroid adenoma 8140/0
    • Secondary, mesenchymal and other tumours

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