Background
Methods
Results
Author | Reference | Journal | Year |
---|---|---|---|
Sobol RE | Hormone-negative, chromogranin A-positive endocrine tumors. | New England Journal of Medicine | 1989 |
Schmid KW | “Atypical” medullary thyroid carcinoma with little or no calcitonin expression. | Virchows Archive A Pathological Anatomy and Histopathology | 1998 |
Redding AH | Normal preoperative calcitonin levels do not always exclude medullary thyroid carcinoma in patients with large palpable thyroid masses. | Thyroid | 2000 |
Bockhorn M | Lack of elevated serum carcinoembryonic antigen and calcitonin in medullary thyroid carcinoma. | Thyroid | 2004 |
Sand M | Serum calcitonin negative medullary thyroid carcinoma. | World journal of surgical oncology. | 2006 |
Dora JM | Normal perioperative serum calcitonin levels in patients with advanced medullary thyroid carcinoma: case report and review of the literature. | Thyroid | 2008 |
Wang TS | Medullary thyroid carcinoma without marked elevation of calcitonin: a diagnostic and surveillance dilemma. | Thyroid | 2008 |
Giovanella L | Serum calcitonin-negative medullary thyroid carcinoma: role of CgA and CEA as complementary markers. | The International Journal of Biological Markers | 2008 |
Alapat DV | Disparity between tissue and serum calcitonin and CEA in patient with medullary thyroid carcinoma. | Endocrine | 2011 |
Chernyavsky VS | Calcitonin-negative neuroendocrine tumor of the thyroid: a distinct clinical entity. | Thyroid | 2011 |
Nakazawa T | C-cell-derived calcitonin-free neuroendocrine carcinoma of the thyroid: the diagnostic importance of CGRP immunoreactivity. | International journal of surgical pathology. | 2011 |
Frank-Raue K | Prevalence and clinical spectrum of nonsecretory medullary thyroid carcinoma in a series of 839 patients with sporadic medullary thyroid carcinoma. | Thyroid | 2013 |
Ismi O | Calcitonin-negative neuroendocrine tumor of thyroid gland mimicking anaplastic carcinoma: an unusual entity. | Gland Surgery | 2014 |
Brutsaert EF | Medullary thyroid cancer with undetectable serum calcitonin. | The Journal of clinical endocrinology and metabolism. | 2014 |
Kim JY | A calcitonin-negative neuroendocrine tumor derived from follicular lesions of the thyroid. | Endocrinology and metabolism. | 2015 |
Kasajima A | A Calcitonin Non-producing Neuroendocrine Tumor of the Thyroid Gland. | Endocrine pathology. | 2016 |
Samà MT | Clinical challenges with calcitonin-negative medullary thyroid carcinoma. | Journal of cancer research and clinical oncology | 2016 |
Parmer M | Calcitonin-Negative Neuroendocrine Tumor of the Thyroid. | International journal of surgical pathology. | 2017 |
Zhou Q | Clinical and pathological analysis of 19 cases of medullary thyroid carcinoma without an increase in calcitonin. | Experimental and toxicologic pathology: official journal of the Gesellschaft für Toxikologische Pathologie. | 2017 |
Demographic and clinicopathological features
Author | Gender | Age (years) | Size (mm) | Histology | CT-HIC | CT | Assay | Upper reference limit | |
---|---|---|---|---|---|---|---|---|---|
1 | Sobol | F | 82 | 20 | WDMTC | Negative | Normal limits | NA | NA |
2 | Schmid 1 | M | 28 | NA | WDMTC | Weak | NA | Immunotech | NA |
3 | Schmid 2 | M | 46 | NA | WDMTC | Weak | NA | Immunotech | NA |
4 | Schmid 3 | F | 45 | NA | WDMTC | Weak | NA | Immunotech | NA |
5 | Schmid 4 | M | 37 | NA | WDMTC | Negative | NA | Immunotech | NA |
6 | Redding | F | 31 | 45 | WDMTC | Diffuse | 28 | RIA | < 150 |
7 | Bockhorn | F | 50 | 20 | PDMTC | Weak | 0.8 | Nichols | < 4.6 |
8 | Sand | F | 73 | NA | PDMTC | Weak | 5.3 | Nichols | < 10 |
9 | Dora | M | 43 | 20 | PDMTC | Diffuse | 4 | Immunolite | < 12 |
10 | Wang | M | 68 | 70 | WDMTC | Weak | 38 | NA | < 10 |
11 | Giovanella | F | 43 | 48 | WDMTC | Diffuse | 4.7 | Immunolite | < 10 |
12 | Alapat | F | 16 | 30 | WDMTC | Diffuse | 4 | Immunolite | < 4.6 |
13 | Chernyavsky | F | 40 | 20 | WDMTC | Negative | 2.1 | Ventana Medical System Inc. | < 5.0 |
14 | Nakazawa | M | 76 | 60 | WDMTC | Weak | 22 | NA | < 10 |
15 | Frank-Raue 1 | F | 61 | 10 | WDMTC | Weak | 2.9 | Nichols | < 10 |
16 | Frank-Raue 2 | M | 70 | 80 | WDMTC | Weak | < 2 | DiaSorin | < 6.1 male < 3.6 female |
17 | Frank-Raue 3 | F | 50 | 20 | WDMTC | Weak | 0.8 | Nichols | < 10 |
18 | Frank-Raue 4 | M | 47 | 30 | PDMTC | Focal | 2.6 | Immunolite | < 8.4 male < 5 female |
19 | Frank-Raue 5 | F | 53 | 45 | WDMTC | Diffuse | NA | NA | NA |
20 | Frank-Raue 6 | M | 45 | 18 | PDMTC | Weak | 11 | Non commercial | < 18 |
21 | Frank-Raue 7 | F | 45 | 55 | PDMTC | Focal | 1.5 | CIS | < 10 |
22 | Ismi | NA | 57 | NA | PDMTC | Negative | 5.6 | NA | < 10 |
23 | Brutsaert | F | 49 | 26 | WDMTC | Diffuse | < 2 | NA | < 6 |
24 | Kim | M | 34 | 10 | PDMTC | Negative | 3.7 | NA | < 10 |
25 | Kasajima | F | 48 | 30 | WDMTC | Negative | 29 | NA | NA |
26 | Samà 1 | M | 60 | 38 | NA | Focal | 7.8 | NA | NA |
27 | Samà 2 | F | 66 | NA | NA | NA | 5 | NA | NA |
28 | Samà 3 | M | 53 | 12 | NA | Negative | < 10 | NA | NA |
29 | Samà 4 | M | 62 | 45 | NA | Focal | 13 | NA | NA |
30 | Parmer | F | 74 | 20 | WDMTC | Negative | Normal limits | NA | NA |
31–49 | Zhou | 11 M 8 F | ≥30 3 cases; < 30 16 cases | ≤10mmm 14 cases > 10 mm 5 cases | NA | Positive in 8 cases Negative in 11 cases | NA | NA | NA |
Preoperative evaluation and surgery
Author | CT serum levels | CEA serum | Cytological examination | Immunohistochemistry |
---|---|---|---|---|
Sobol | Normal limits | NA | NA | NA |
Schmid 1 | NA | NA | NA | NA |
Schmid 2 | NA | NA | NA | NA |
Schmid 3 | NA | NA | NA | NA |
Schmid 4 | NA | NA | NA | NA |
Redding | 8.2 pg/mL | NA | Atypical cells not diagnostic of MTC | Positive for calcitonin |
Bockhorn | 0.8 pg/mL | Normal limits | Suspicious for MTC or anaplastic cancer | NA |
Sand | 5.3 pg/mL | NA | NA | NA |
Dora | 4.0 pg/mL | 0.78 ng/mL | Atypias suggesting for malignancy | NA |
Wang | 38 pg/mL | 56.7 ng/mL | Discohesive cells with eccentric nuclei, finely granular chromatin and relatively uniform morphology | Negative for calcitonin |
Giovanella | 4.7 pg/mL | 12.8 ng/mL | Aggregates of elonged cells with finely granular cytoplasm and oval nuclei with coarsely clumped chromatin and nuclear pseudoinclusions | Positive for calcitonin |
Alapat | 4.0 pg/mL | 1.0 ng/mL | Positive for MTC | Positive for MTC |
Chernyavsky | 2.1 pg/mL | 0.5 ng/mL | Findings suspicious for a poorly differentiated carcinoma with neuroendocrine differentiation | Negative for calcitonin |
Nakazawa | 22 pg/mL | NA | Several solid cell clusters | NA |
Frank-Raue 1 | 2.9 pg/mL | 1.3 ng/mL | Suspected malignancy | NA |
Frank-Raue 2 | ≤2 pg/mL | 2.1 ng/mL | NA | NA |
Frank-Raue 3 | < 0.8 pg/mL | 2.8 ng/mL | Positive for MTC | NA |
Frank-Raue 4 | 2.6 pg/mL | 3.1 ng/mL | NA | NA |
Frank-Raue 5 | Normal limits | Normal limits | NA | NA |
Frank-Raue 6 | 11 pg/mL | Normal limits | NA | NA |
Frank-Raue 7 | 1.5 pg/mL | 1.7 ng/mL | NA | NA |
Ismi | 5.6 pg/mL | Normal limits | NA | NA |
Brutsaert | 2.1 pg/mL | 3.1 ng/mL | Positive for malignant cells | Positive for calcitonin in isolated cells |
Kim | 3.7 pg/mL | NA | Positive for MTC | NA |
Kasajima | 29 pg/mL | NA | Positive for MTC | Negative for calcitonin |
Samà 1 | 7.8 pg/mL | NA | NA | NA |
Samà 2 | 5 pg/mL | NA | NA | NA |
Samà 3 | < 10 pg/mL | 1.8 ng/mL | NA | NA |
Samà 4 | 13 pg/mL | 6.3 ng/mL | NA | NA |
Parmer | NA | NA | Suspected malignancy | NA |
Zhou | NA | NA |
Author | Surgery | Tumor grading | Follow-up | Recurrence | CT-IHC | CGRP-IHC | CgA-IHC | Syn-IHC | TG-IHC | CEA-IHC | RET mutation |
---|---|---|---|---|---|---|---|---|---|---|---|
Sobol | TT | WDMTC | 6 month | Lymph nodes, liver and bone | – | – | + | NA | NA | + | NA |
Schmid 1 | NA | WDMTC | NA | NA | NA | + | + | NA | – | – | NA |
Schmid 2 | NA | WDMTC | 19 month | Lymph nodes | NA | + | + | NA | – | – | NA |
Schmid 3 | NA | WDMTC | NA | NA | NA | – | + | NA | – | – | NA |
Schmid 4 | NA | WDMTC | NA | NA | NA | – | + | NA | NA | – | NA |
Redding | TT + LYA | WDMTC | 43 month | Negative | + | NA | NA | + | NA | + | – |
Bockhorn | TT + LYA | PDMTC | NA | NA | NA | NA | + | NA | – | + | + |
Sand | TT + LYA | PDMTC | Deceased 6 weeks | NA | NA | NA | NA | NA | NA | NA | NA |
Dora | TT | PDMTC | NA | NA | + | NA | + | + | – | NA | – |
Wang | NA | WDMTC | 12 months | Negative | + | NA | + | NA | – | + | NA |
Giovanella | TT + LYA | WDMTC | 24 months | NA | + | NA | NA | NA | NA | NA | NA |
Alapat | TT + LYA | WDMTC | 20 months | Negative | + | NA | + | NA | – | + | NA |
Chernyavsky | TT + LYA | WDMTC | 12 months | Negative | – | NA | + | + | + | NA | + |
Nakazawa | TT | WDMTC | 18 months | Negative | NA | NA | + | + | – | NA | NA |
Frank-Raue 1 | ET | WDMTC | 72 months | Negative | + | NA | + | + | – | + | – |
Frank-Raue 2 | NA | WDMTC | 25 months | Pulmonary | + | NA | + | + | – | + | – |
Frank-Raue 3 | NA | WDMTC | 150 months | Lymph modes | + | NA | + | + | – | + | + |
Frank-Raue 4 | NA | PDMTC | 18 months | Local tumor infiltration | + | NA | + | + | – | + | – |
Frank-Raue 5 | NA | WDMTC | 21 months | Lymph node, bone, brain | + | NA | + | + | – | + | + |
Frank-Raue 6 | NA | PDMTC | 21 months | Pulmonary | + | NA | + | + | – | + | + |
Frank-Raue 7 | NA | PDMTC | 36 months | Dead because of pulmonary failure | + | NA | + | + | – | + | + |
Ismi | NA | PDMTC | NA | NA | – | NA | + | + | – | NA | NA |
Brutsaert | TT + LYA | WDMTC | NA | NA | NA | NA | NA | NA | NA | NA | + |
Kim | ET | PDMTC | 12 months | Negative | – | NA | + | + | + | – | – |
Kasajima | NA | WDMTC | NA | NA | NA | + | + | + | NA | NA | – |
Samà 1 | TT | NA | 120 months | Negative | + | NA | + | NA | NA | + | – |
Samà 2 | NA | NA | 120 months | Negative | NA | NA | NA | NA | NA | NA | NA |
Samà 3 | NA | NA | 36 months | Negative | – | NA | – | NA | NA | – | + |
Samà 4 | NA | NA | 36 months | Negative | + | NA | + | NA | NA | – | – |
Parmer | TT | WDMTC | NA | NA | – | NA | + | + | – | + | NA |
Zhou | NA | NA | NA | NA | + 8 cases - 11 cases | NA | + 18 cases - 1 case | + 19 cases | + 5 cases - 14 cases | + 4 cases - 15 cases | NA in 15 cases - In 4 cases |
Definitive pathology examination and immunohistochemistry
Authors | Cell morphological characteristics | Neuroendocrine tumor structure | Amyloid substance | Lymph node metastasis | Thyroid capsular invasion | Vascular tumor thrombus |
---|---|---|---|---|---|---|
Sobol | Ovoid-to-spindle-shaped in groups divided by fibrous septum | Neurosecretory granules | Focal | NA | NA | NA |
Schmid 1 | Polygonal and spindle cells | NA | NA | NA | Negative | Negative |
Schmid 2 | Polygonal and spindle cells | NA | NA | NA | Negative | Negative |
Schmid 3 | Polygonal and spindle cells | NA | NA | NA | Positive | Positive |
Schmid 4 | Polygonal and spindle cells | NA | NA | NA | Positive | Positive |
Redding | Nets of fairly uniform cells | NA | NA | NA | Negative | NA |
Bockhorn | Polyhedral and spindle cells | Positive | NA | NA | Negative | NA |
Sand | NA | NA | NA | Positive | Positive | Positive |
Dora | Spindle-shaped celss | NA | Positive | Positive | Positive | Positive |
Wang | NA | NA | Negative | Positive | Positive | Positive |
Giovanella | Elongated cells | NA | NA | NA | NA | NA |
Alapat | Spindle-round-polygonal cells | NA | NA | Positive | Positive | Positive |
Chernyavsky | Fairly uniform round and polygonal cells | Positive | NA | Negative | Negative | Negative |
Nakazawa | “Zellballen” pattern | NA | NA | Negative | Negative | Negative |
Frank-Raue 1 | NA | NA | NA | NA | NA | NA |
Frank-Raue 2 | NA | NA | NA | NA | NA | NA |
Frank-Raue 3 | NA | NA | NA | NA | NA | NA |
Frank-Raue 4 | NA | NA | NA | NA | NA | NA |
Frank-Raue 5 | NA | NA | NA | NA | NA | NA |
Frank-Raue 6 | NA | NA | NA | NA | NA | NA |
Frank-Raue 7 | NA | NA | NA | NA | NA | NA |
Ismi | Atypical cells | Positive | NA | NA | NA | NA |
Brutsaert | NA | NA | NA | Negative | Positive | Negative |
Kim | NA | Positive | NA | Negative | Negative | Negative |
Kasajima | Polygonal-spindle-shaped cells | Positive | NA | Negative | Negative | Negative |
Samà 1 | Small-spindle cells | Positive | Positive | NA | NA | NA |
Samà 2 | NA | NA | NA | NA | NA | NA |
Samà 3 | NA | NA | NA | NA | NA | NA |
Samà 4 | NA | NA | NA | NA | NA | NA |
Parmer | Spindle-round cells | NA | Negative | NA | NA | NA |
Zhou | Polygonal cells in 17 cases Spindle cells in 2 cases | Positive in 16 cases Negative in 3 cases | Positive in 11 cases Negative in 8 cases | Positive in 3 cases Negative in 16 cases | Positive in 8 cases Negative in 11 cases | Positive in 1 case Negative in 18 cases |