الفهرس 
Papillary thyroid carcinoma (PTCOnly 14 pages are availabe for public view
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Abstract
P
apillary thyroid carcinoma (PTC) is the most common thyroid malignancy. The diagnosis of PTC is based on nuclear features, however identification of these features is inconsistent and controversial, and accordingly the microscopic distinction of PTC from other benign thyroid lesions may be difficult.
In a few cases, the histopathology of papillary thyroid hyperplasia and PTC may be similar enough to cause a diagnostic dilemma.
The most common challenge in thyroid pathology is differentiating FVPTC from other follicular patterned nodules such as hyperplasyic nodule, follicular adenoma and follicular carcinoma . The distinction is critical for prognosis and management. The interobserver variability in this area is well recognized. This interobserver variability is particularly true for encapsulated follicular lesions with partial or incomplete features of PTC. The term WDT-UMP has been proposed for such lesions in which the nuclear features are not well developed. However, uncertainty remains about the nature of these lesions and their relationship to PTC.
In an attempt to resolve these diagnostic difficulties, several immunostains have been proposed to aid in the diagnosis and differential diagnosis of PTC including HBME-1, CK19, CIIED1, galectin-3 and others.
HBME-1 is a monoclonal antibody directed against the microvillous surface of mesothelial cells. Several studies have demonstrated HBME-1 usefulness in distinguishing PTC from benign thyroid lesions. HBME-1 shows diffuse strong immunostaining in the majority of PTCs, whereas it is usually absent or showed only weak and focal immunoreactivity in benign thyroid lesions.
Similarly CK19 a cytoskeleton intermediate filament protein, has been found to be a good marker for PTC. CK19 shows diffuse strong immunoreactivity in the majority of PTCs, whereas it is usually absent or focally expressed in benign thyroid lesions.
This work aims at evaluating the expression of anti-HBME-1 and CK19 antibodies in the PTC and benign thyroid lesions, in an attempt to evaluate their possible diagnostic utility either singly or in combination in routine practice regarding the diagnosis and differentiation of PTCs from their benign mimics especially when dealing with encapsulated follicular patterned lesions with questionable PTC-type nuclear features.
The study was conducted on 52 selected cases of different surgically removed thyroid lesions which were received at Ain Shams University Hospital and Specialized Ain Shams University Hospital during the period from July 2007 to July 2009.
All the selected 52 cases were previously diagnosed and classified into:
A) 24 cases of PTC.
B) 23 cases of benign thyroid lesions.
C) 5 cases of atypical thyroid nodules with atypical nuclear features.
All the selected 52 cases underwent histopathological reevaluation.
Furtherly all the cases after histopathological reevaluation were subjected to the following:
Clinicopathological study: available clinicopathhological data were recorded including age and sex of the patients, size and multiplicity of the lesions extrathryoid extension and lymph node metastases in case of malignancy.
Immunohistochemical study: immunostaining with anti-HBME-1 and CK19 antibodies was done using streptavidin-biotin immunoperoxidase technique.The following parameters were assessed:
- The pattern of HBME-1 immunoreactivity was considered positive when it is expressed in the cell membrane with apical luminal accentuation either associated with cytoplasmic immunostaining or not. While CK19 immunoreactivity was considered positive when it is expressed in the cytoplasm with membraneous accentuation.
- Both HBME-1 and CK19 expression were judged as negative if <10% of tumor cells were stained positive, focal positive if 10-50% of tumor cells were stained positive, diffuse positive if >50% of tumor cells were stained positive.
The studied 52 cases were histopathologically reevaulated and classified into:
1- 25 cases of PTC.
2- 16 cases of benign thyroid lesions.
3- 11 cases of atypical thyroid nodules with questionable PTC type nuclear features which labled as WDT-UMP.
The results showed HBME-1 immunoreactivity was positive in 92% of PTC cases compared to 96% of CK19 with the majority of cases showed diffuse strong immunostaining. In the benign thyroid lesions HBME-1 immunoreactivity was negative in all cases, compared to 68.8% of CK19
Both HBME-1 and CK19 immunoractivity showed highly statistically significant difference between PTC and benign thyroid lesions.HBME-1 showed higher specificity,PPV and diagnostic accuracy than CK19, while CK19 showed slightly higher sensitivity and NPV. The combined expression of HBME-1 and CK19 markedly enhanced the specificity, PPV and diagnostic accuracy of CK19. In case of HBME-1 the diagnostic indices of the coexpression were very close to that of HBME-1 alone.
It was also found that diagnostic indices of HBME-1 in differentiating PTC with papillary configuration and benign papillary with thyroid hyperplasia were higher than those of CK19; and that the diagnostic indices of the coexpression were similar or slightly lesser than those of HBME-1 alone.
It was also found that HBME-1 specificity, PPV and diagnostic accuracy was higher than those of CK19 in differentiating between FVPTC and follicular patterned nodules, while CK19 revealed a higher sensitivity and NPV reached 100%. The coexpression of both markers was similar to those of HBME-1.
There were statistically significance difference between PTC, WDT-UMP1 and benign thyroid lesions as regards the distribution of HBME-1 immunoreactivity. As for CK19 expression there were significant difference between PTC and WDT-UMP cases, but no statistical significance between WDT-UMP and benign cases.
On the basis of the results of this study; that showed a complementary nature of the combined utility of HBME-1 and CK19; a protocol was suggested to identify various degree of risk potential for malignancy as follow:
a. Definite malignancy can be supposed if:
i. Both HBME-1 and CK19 are diffusely expressed.
ii. HBME-1 alone is diffusely expressed.
iii. CK19 is diffusely expressed and HBME-1 is focally expressed.
b. Suspicious of malignancy can be suggested if:
CK19 is diffusely expressed and HBME-1 is negative.
c. Well differentiated tumor of uncertain malignant potential (borderline lesion) for strict follow up can be suggested if:
i. HBME-1 and CK19 are focally expressed.
ii. HBME-1 is focally expressed and CK19 is negative.
d. Benign diagnosis can be considered if:
i. HBME-1 and CK19 are negative.
ii. HBME-1 is negative and CK19 is focally expressed.
Therefore, on the basis of the results of this study it is recommended that HBME-1 and CK19 are highly suggested for use in diagnosing and differentiating PTC cases from their benign mimics especially when dealing with encapsulated follicular lesions with questionable PTC type nuclear features. Additional researches and follow up studies on large numbers of cases should be conducted to throw the light on the exact nature of these cases with questionable PTC type nuclear features and to validate exactly the role of HBME-1 and CK19 as diagnostic markers in routine work for such challenging cases.