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Biomedical subjects

Zubair W Baloch

Publications and source records attributed to Zubair W Baloch.

At least 19 recordsLinked to original sources

Endoscopic ultrasound guided fine needle aspiration of non-pancreatic lesions: an institutional experience.

BACKGROUND: Endoscopic ultrasound guided fine needle aspiration biopsy (EUS-FNA) has proven to be an effective diagnostic modality for the detection and staging of pancreatic malignancies. In recent years EUS-FNA has also been used to diagnose lesions of non-pancreatic sites such as structures in close proximity to the gut wall within the mediastinum, abdomen, pelvis and retro-peritoneum. AIMS: To evaluate experience with EUS-FNA of non-pancreatic sites at a large university medical centre. METHODS: The study cohort included 234 patients who underwent EUS-FNA of 246 lesions in non-pancreatic sites (122 peri-pancreatic and coeliac lymph nodes; 9 peri-pancreatic masses; other sites: mediastinum 12, gastric 25, liver 27, oesophagus 17, duodenum/colon/rectum 15, retro-peritoneum 8, lung 7, miscellaneous 4). RESULTS: The cytology diagnoses were classified as non-neoplastic/reactive in 82 (33%), atypical/suspicious for malignancy in 25 (10%), malignant in 86 (35%) and non-diagnostic in 53 (22%) cases. Surgical pathology follow-up was available in 75 (31%) cases. Excluding the non-diagnostic cases there were 7 false negative and 3 false positive cases. The sensitivity, specificity and positive predictive value of EUS-FNA in the diagnosis of lesions of non-pancreatic sites was 92%, 98% and 97%, respectively. CONCLUSIONS: EUS-FNA can be effectively used as a diagnostic modality in the diagnosis of lesions from non-pancreatic sites.

Adolescent↗

Lack of BRAF mutations in hyalinizing trabecular neoplasm.

The hyalinizing trabecular neoplasm (HTN) of the thyroid is an unusual and controversial lesion. Some consider it a peculiar type of papillary thyroid carcinoma (PTC) because of its nuclear features and presence of psammoma bodies. Others consider it an adenoma. Molecular studies have found RET/PTC translocations in some examples, supporting HTN as a PTC; however mutations in BRAF (another marker for PTC) have not been found. We report two cases of classic HTN and a case of trabecular PTC and show BRAF mutations in the latter and not in HTN. Trabecular growth pattern is insufficient for a diagnosis of HTN and lesions with such a pattern and nuclear features of PTC are cancers. Morphologically classic HTN are not associated with metastatic potential and should be considered adenomas.

Journal Article↗

Diagnostic utility of mucin profile in fine-needle aspiration specimens of the pancreas: an immunohistochemical study with surgical pathology correlation.

BACKGROUND: The cytologic differentiation between neoplastic and reactive/reparative processes in the endoscopic ultrasound-guided fine-needle aspirations (EUS-FNA) of the pancreas can be difficult. Malignant transformation of the pancreatic ductal epithelium changes the expression of apomucins. The goal of the current study was to determine an optimal immunohistochemical panel of mucin (MUC) antibodies that would allow the cytomorphologic distinction of pancreatic ductal adenocarcinoma and its differentiation from reactive/reparative processes and inadvertently sampled gastric and duodenal mucosa. METHODS: Pancreatic EUS-FNA specimens performed on 351 patients were reviewed. Expression profiles of MUC1, 2, 5AC, and 6 were examined on 56 cell block sections and 26 follow-up pancreatectomy specimens. RESULTS: MUC1 and 6 expression was found in nonneoplastic pancreatic samples, whereas there was an absence of expression of MUC2 and 5AC. MUC2 was detected in mucosal goblets cells of the duodenum, MUC6 in Brunner glands, and MUC5AC in gastric foveolar cells. MUC5AC expression in differentiating ductal adenocarcinomas from benign conditions demonstrated better operating characteristics than either MUC1 or MUC6. The apomucin expression pattern both in cytology and follow-up surgical pathology specimens was similar. In surgical pathology specimens, the panel of 3 antibodies, MUC1+/MUC2-/MUC5AC+, was noted in 15 of 17 ductal carcinomas (88.2%). In nonneoplastic pancreatic tissue, the expression panel MUC1+/MUC2-/MUC5AC- was observed in 14 of 17 (82.4%) cases. In cytology specimens, the combination of MUC1+/MUC2-/MUC5AC+ was noted in 21 of 30 ductal carcinoma cases (70.0%), 3 of 6 atypical cases (50%), and 1 of 1 suspicious for malignancy cases (100%). The combination MUC1+/MUC2-/MUC5AC+ was not observed in any of the negative for malignancy or reactive cases (0 of 6). CONCLUSIONS: The most optimal panel for the diagnosis of ductal adenocarcinoma in both the EUS-FNA specimens is a panel including MUC1/MUC2/MUC5AC, whereas a panel of all 4 antibodies (MUC1, 2, 5AC, and 6) will in addition aid in differentiating inadvertently sampled normal/reactive duodenal and gastric epithelium from neoplastic pancreatic tissue.

Adolescent↗

Our approach to follicular-patterned lesions of the thyroid.

Follicular-patterned lesions of the thyroid are common; these include hyperplastic/adenomatoid nodules, follicular adenoma, follicular carcinoma and follicular variants of papillary carcinoma. Most of these lesions can be diagnosed with ease; however, there is a controversial subgroup. In this review, we present our diagnostic approach based on our experience with the histological diagnosis of these tumours, which can help in appropriate clinical management.

Adenocarcinoma, Follicular↗

Fine-needle aspiration of follicular lesions of the thyroid. Diagnosis and follow-Up.

The differential diagnosis of a follicular lesion/neoplasm in thyroid FNA specimens includes hyperplastic/adenomatoid nodule, follicular adenoma and carcinoma, and follicular variant of papillary thyroid carcinoma. In our laboratory we separate follicular lesions of thyroid into hyperplastic/adenomatoid nodule (HN), follicular neoplasm (FON) and follicular derived neoplasm with focal nuclear features suspicious for papillary thyroid carcinoma (FDN). This study reports our experience with 339 cases diagnosed as FON and 120 as FDN. All cases were evaluated for histologic diagnosis, age, sex and size of the nodule. Histopathologic follow-up was available in all cases. The malignancy rate was 22% (74/359) and 72% (86/120) for cases diagnosed as FON and FDN, respectively. In the FON category almost half of the malignant cases were papillary carcinoma. The risk of malignancy was higher in patients younger than 40 yr (53% vs. 30%) than in patients 40 year or more years old and greater in males (41% vs. 33%) than females. No statistically significant relationship was noted between the sizes of the nodules and benign vs. malignant diagnosis. According to this study it is important to divide follicular patterned lesions of thyroid into FON and FDN in the cytology specimens due to significantly different risk of malignancy (22% vs. 72%). In addition, clinical features, including gender and age can be part of the decision analysis in selecting patients for surgery.

Journal Article↗

Microcarcinoma of the thyroid.

Thyroid microcarcinoma, defined as a thyroid tumor measuring 1 cm or less, is an extremely indolent tumor. Papillary microcarcinoma, the most common subtype, is often identified incidentally in a thyroid removed for benign clinical nodules or diffuse processes (eg, thyroiditis). In this clinical situation, over 99% are cured by simple lobectomy. In the less common scenario, the microcarcinoma is the primary lesion to a lymph node metastasis presenting clinically as a neck mass; in this situation, the tumor should be treated as a clinical cancer. Other rare microcarcinomas can occur and, of these, the most recently described is micromedullary carcinoma. In the familial setting, these lesions are identified in prophylactic thyroidectomies and are not unexpected findings. However, when found as sporadic tumors, their implications are still unknown. The histologic features, pathologic mimics, and molecular facets of these microscopic neoplasms are discussed in this review.

Adenocarcinoma, Follicular↗

Assessing the utility of a mutational assay for B-RAF as an adjunct to conventional fine needle aspiration of the thyroid gland.

Thyroid carcinoma is the most common endocrine malignancy; it is typified by a number of classical genomic insults, which tend to cluster with the discrete histologic subtypes. The most common of these is a mutation in B-RAF, which is present in approximately 44% (29% to 83%) of cases. In this review we have assessed the potential utility of a molecular test for somatically acquired mutations in B-RAF using thyroid malignancy as a model system according to 3 fundamental questions: would a test enhance our ability to distinguish benign from malignant, would a test unveil a risk factor not otherwise known, and would detecting a mutation enable a therapeutic option specific to those patients who carry the mutation?

Adolescent↗

Cytologic and architectural mimics of papillary thyroid carcinoma. Diagnostic challenges in fine-needle aspiration and surgical pathology specimens.

In this paper, we review those pathologic entities that may mimic papillary thyroid carcinoma. These include specimen preparation and handling issues such as decalcification, frozen section, and artifacts occurring following fine-needle aspiration (FNA). Also discussed are true disease entities, including chronic lymphocytic thyroidits, benign papillary hyperplastic lesions, hyalinizing trabecular neoplasm, and post-FNA changes. Both the cytologic and histopathologic preparations containing these changes are reviewed and illustrated; guidelines for distinctions among these entities are provided.

Biopsy, Fine-Needle↗

Is fine-needle aspiration (FNA) of multiple thyroid nodules justified?

BACKGROUND: The clinical management of patients with solitary thyroid nodule is well established; however, the evaluation of patients with multiple thyroid nodules is controversial. The aim of this study was to assess if there is a correlation between the risk of malignancy and number of thyroid nodules. DESIGN: The study cohort included 2,884 patients (2,410 females and 474 males) with 3,274 thyroid nodules that underwent FNA under ultrasound guidance between November 1997 and April 2004. Multiple thyroid nodules were aspirated in 360 patients; 2 in 332 (291 females, 41 males), 3 nodules in 26 (23 females, 3 males), and 4 nodules in 2 patients (1 female, 1 male). Subsequent information regarding the histological diagnosis was obtained in the cases that underwent surgical excision. RESULTS: The average age for patients with single or multiple nodules was the same (51 yr). The FNA specimens were diagnosed as benign (n = 1,663, 51%), neoplasm (n = 880, 27%), suspicious for neoplasm or papillary carcinoma (n = 234, 7%), malignant (n = 187, 6%), and non-diagnostic (n = 310, 9%). Surgical excision was performed in 1,135 patients: 993 patients with single nodules and 142 patients with multiple nodules. The surgical pathology diagnosis was benign in 656 nodules (52%) and malignant in 596 nodules (48%). In the malignant category 153 tumors were papillary microcarcinoma (<1 cm). Excluding these cases, the malignancy rate was 39% in patients with single nodules, 41% with two nodules, and 21% with three nodules. CONCLUSIONS: The cancer risk is similar for patients with one or two nodules over 1 cm and decreases with three or more thyroid nodules.

Biopsy, Fine-Needle↗

Relative accuracy of fine-needle aspiration and frozen section in the diagnosis of lesions of the parotid gland.

BACKGROUND: Both fine-needle aspiration (FNA) and frozen section (FS), although useful in preoperative and intraoperative management, have their advantages and pitfalls when used in the diagnosis of salivary gland lesions. The accuracy of each of these modalities has been assessed separately in many studies; a direct comparison of these techniques on a large cohort has not been well studied. Herein, we determine the relative accuracies of both FNA and FS in the diagnosis of salivary gland lesions. METHODS: We reviewed a cohort of 220 cases of parotid gland FNA with histologic follow-up; FS was performed in 57 cases (26%). The sensitivity, specificity, and accuracy of FNA and FS were determined with respect to the final histologic diagnosis. For these calculations, benign diagnosis was considered negative, whereas a malignant diagnosis was considered positive. In addition, we re-reviewed the FNA and FS slides in cases that had conflicting FNA and FS results. RESULTS: Of the 220 cases examined, the FNA diagnoses were as follows: benign (n = 142), malignant (n = 52), indeterminate (n = 14), and nondiagnostic (n = 12). Correlating these findings with the histologic findings, nine cases (4%) were false negative, whereas 12 (5%) were false positive. The sensitivity, specificity, and accuracy for FNA when diagnostic were 86%, 92%, and 90%, respectively. In 57 cases with FS, seven (12%) were false negative, whereas none were false positive. The FS was able to change to benign four diagnoses that were malignant by FNA and provide a diagnosis for five nondiagnostic FNAs. The sensitivity, specificity, and accuracy for FS were 77%, 100%, and 88%, respectively. The sensitivity, specificity, and accuracy for FNA and FS combined were 90%, 100%, and 95%, respectively. CONCLUSIONS: Both FNA and FS provide a similar accuracy. FS may be useful if FNA is nondiagnostic and may also be useful in confirming or refuting malignancy in some cases. Hence, both techniques are complementary to each other in the diagnosis of salivary gland lesions.

Adenolymphoma↗

Comparison of p63 and p73 expression in benign and malignant salivary gland lesions.

BACKGROUND: The p63 and p73 genes are members of the p53 family and play an important role in stem cell identity and cellular differentiation and are expressed in basal and myoepithelial cells. In this study, we examined the expression of p63 and p73 in 50 various benign salivary gland lesions and 45 malignant salivary gland tumors. METHODS: The 95 salivary gland tumors were selected from the archives of the Department of Pathology and Laboratory Medicine at the Hospital of the University of Pennsylvania. Sectioned formalin-fixed paraffin-embedded tissue cut at 3 mum was immunostained with antibodies that recognize all isozymes of p63 and p73 and evaluated with respect to percentage of positive cells and localization. RESULTS: In benign lesions, p63 and p73 nuclear reactivity was seen in 46 (92%) of 50 and 47 (94%) of 50 cases, respectively. In malignant tumors, p63 and p73 were seen in 34 (76%) of 45 and 40 (89%) of 45 cases, respectively. A significant difference between p63 and p73 positivity was only seen in adenoid cystic carcinomas (p = .006). Also, p73 was found in tumors with minimal basal/myoepithelial differentiation. CONCLUSIONS: Hence, p63 and p73 expression is retained in both benign and malignant salivary gland tumors with basaloid or myoepithelial differentiation. Hence, p63 seems to be a more specific marker of myoepithelial differentiation than p73.

Biomarkers, Tumor↗

Lymphatic and blood vessel density in the follicular patterned lesions of thyroid.

The histologic distinction of follicular patterned lesions of thyroid, that is follicular adenoma, follicular carcinoma, and the follicular variant of papillary thyroid carcinoma can be extremely difficult. The differential diagnostic criteria regarding nuclear features of papillary thyroid carcinoma are subjective, resulting in high interobserver variability. Although papillary thyroid carcinoma metastasizes mainly via lymphatic vessels, whereas follicular carcinoma spreads mostly hematogenously, there are no data regarding utility of objective quantitative criteria such as lymphatic and general blood vessel density for the differential diagnosis of these lesions. In this study, 35 follicular patterned lesions of thyroid (14 follicular adenomas, 10 follicular carcinomas, and 11 of the follicular variant of papillary thyroid carcinomas) were evaluated immunohistochemically. An assessment of intra- and peritumoral lymphatic vessel density was performed using novel lymphatic endothelium-specific marker D2-40, and the intra- and peritumoral general vessel density was determined by the panendothelial marker CD31. There were no significant differences in the intra- and/or peritumoral general vessel densities, and peritumoral lymphatic vessel densities among follicular adenoma, follicular carcinoma and the follicular variant of papillary thyroid carcinoma. In contrast, the intratumoral lymphatic vessel density was significantly higher in the follicular variant of papillary thyroid carcinoma than in either follicular adenoma or follicular carcinoma (34.63, 15.04, and 0.11 respectively; P<0.0001). The results of the study show that intratumoral lymphatic vessel density may serve as a useful tool in the differential diagnosis of follicular patterned lesions of thyroid.

Adenocarcinoma, Follicular↗

Granular cell tumor of the thyroid: a case report.

We report a rare case of granular cell tumor (GCT) arising within the thyroid parenchyma. The differential diagnosis of GCT in thyroid includes all oncocytic/Hürthle cell lesions of the thyroid, medullary carcinoma and metastasis. The classic histomorphologic features and immunohistochemistry are helpful in arriving at the correct diagnosis.

Adenoma, Oxyphilic↗

Use and abuse of frozen section in the diagnosis of follicular thyroid lesions.

The role of intraoperative frozen section in certain organ systems such as the thyroid continues to be problematic. In many cases, diagnoses are deferred or nonhelpful--"follicular lesion." In the modern era, the widespread use of preoperative aspiration biopsy has allowed for more careful selection of patients who undergo thyroid surgery. In many cases, the fine-needle-aspiration (FNA) biopsy diagnosis can be definitive or can guide the specific surgical procedure. The literature supports our approach, which is summarized as follows: Intraoperative consultation is not needed on the intrathyroidal nodule if a preoperative FNA was definitive for papillary carcinoma. Frozen section is of no value in the intraoperative diagnosis of lesions diagnosed on FNA as "follicular neoplasm" or "Hürthle cell neoplasm" because the characterization of these lesions requires detailed analysis of the tumor capsule for the demonstration of capsular and/or vascular invasion--an analysis that is not practical in the intraoperative setting. Finally, intraoperative consultation including frozen section and intraoperative cytologic examination is most useful in those cases that are diagnosed as suspicious for papillary carcinoma by FNA, because the assessment of nuclear features needed for the definitive diagnosis is possible with intraoperative techniques in a significant number of cases.

Biopsy, Fine-Needle↗

Pathologic diagnosis of papillary thyroid carcinoma: today and tomorrow.

Papillary thyroid carcinoma is the most common malignancy of the thyroid. It is a well-differentiated tumor and the majority behaves in an indolent fashion. The pathologic diagnosis of papillary carcinoma in both cytology and histologic specimens is based upon demonstration of typical nuclear morphology. Using these morphologic criteria, most papillary cancers can be diagnosed with ease, except cases in which there is a paucity of diagnostic nuclear features. Despite advances in the treatment of thyroid cancer, disease recurrences and metastasis can be observed in 20% of cases. Recently, many advances have been made in the pathogenesis of papillary thyroid carcinoma. The notable genetic events include Ret/PTC rearrangements, Ras and BRAF gene mutations. The identification of these has also led to their use in diagnosis and predicting prognosis of papillary thyroid carcinoma. In addition, these involved genes may also serve as targets for cancer chemotherapy in patients where standard thyroid cancer treatment is not effective.

Animals↗

Chronic granulomatous lesions after thyroidectomy: imaging findings.

OBJECTIVE: The purpose of this report is to describe the imaging appearance of granulomatous inflammation in the neck presenting as a late complication in patients who have undergone thyroidectomy for differentiated thyroid carcinoma. CONCLUSION: Granulomatous inflammation can occur as a palpable mass in the operative bed of asymptomatic patients who have undergone thyroidectomy for thyroid carcinoma. The diagnosis may be suggested when the lesion shows the sonographic appearance of a poorly defined hypoechoic lesion or lesions with a central echogenic nonshadowing focus, often within the sternocleidomastoid muscle. These lesions may appear as complex cystic masses on CT and MRI and may have increased activity on PET. Percutaneous biopsy can establish the diagnosis of an inflammatory lesion and can exclude underlying active infection and malignancy.

Aged↗

Can cytomorphology differentiate between benign nodules and tumors arising in Graves' disease?

Fine-needle aspiration (FNA) specimens from thyroid nodules arising in Graves' disease (GD) can pose diagnostic difficulties because the cytomorphologic changes in GD may mimic nuclear features of papillary thyroid carcinoma (PTC). In addition, treatment of GD patients with radioactive iodine (RAI) may cause significant cytologic atypia, further increasing the diagnostic difficulty. From March 1999 to April 2002, a total of 14 hypofunctioning nodules in 9 patients with GD underwent FNA; 3 patients had received RAI treatment. Three cases were diagnosed as suspicious for PTC and 11 as benign. Three patients with the diagnosis of suspicious for PTC on FNA underwent surgery and were found to have papillary carcinoma. We assessed all cases to find key cytologic features that can differentiate between nodules with reactive/reparative nuclear atypia from PTC arising in GD. The cytologic features assessed included cellularity, amount of colloid, monotony of the cell population, oncocytic features, cell crowding, lymphocytic infiltration, nuclear elongation, nuclear grooves, pale powdery chromatin, presence of small eccentric nucleoli, and random nuclear atypia. Each feature was semiquantitatively graded on a sliding scale of 0 to 4, with 0 representing absence and 4 representing a predominance of the feature. The mean value of each feature was calculated and the benign and malignant lesions were compared using the unpaired t-test. Four features were found to be statistically significant in the diagnosis of PTC as compared to the benign nodules in GD. The nuclei of PTC in GD show prominent nuclear elongation, pale powdery chromatin, intranuclear grooves, and small eccentric nucleoli. All other features studied were not found to be statistically significant. There does exist an overlap between the cytologic features of benign nodules and PTC arising in GD. However, adherence to strict diagnostic criteria (nuclear elongation, pale powdery chromatin, intranuclear grooves, and small eccentric nucleoli) can enable the diagnosis of PTC arising in GD.

Adult↗