Myopericytoma (MPC) is a rare tumor with perivascular proliferation of pluripotent stem-cell-like... more Myopericytoma (MPC) is a rare tumor with perivascular proliferation of pluripotent stem-cell-like pericytes. Although indolent, MPC may be locally aggressive with recurrent disease. The pathogenesis and diagnostic biomarkers of MPC are poorly understood. We discovered that 15% of benign MPCs (thyroid, skin; 3 of 20 samples) harbored BRAF(WT/V600E); 33.3% (1 of 3 samples) of BRAF(WT/V600E)-MPCs were multifocal/infiltrative/recurrent. Patient-MPC and primary MPC cells harbored BRAF(WT/V600E), were clonal and expressed pericytic-differentiation biomarkers crucial for its microenvironment. BRAF(WT/V600E)-positive thyroid MPC primary cells triggered in vitro (8.8-fold increase) and in vivo (3.6-fold increase) angiogenesis. Anti-BRAF(V600E) therapy with vemurafenib disrupted angiogenic and metabolic properties (~3-fold decrease) with down-regulation (~2.2-fold decrease) of some extracellular-matrix (ECM) factors and ECM-associated long non-coding RNA (LincRNA) expression, with no effects ...
Thyroid fine-needle aspiration (FNA) cytology is a fast growing field. One of the most developing... more Thyroid fine-needle aspiration (FNA) cytology is a fast growing field. One of the most developing areas is represented by molecular tests applied to cytological material. Patients that could benefit the most from these tests are those that have been diagnosed as "indeterminate" on FNA. They could be better stratified in terms of malignancy risk and thus oriented with more confidence to the appropriate management. Taking in consideration this need to improve and keep high the yield of thyroid FNA, professionals from various fields (i.e. molecular biologists, endocrinologists, nuclear medicine physicians and radiologists) are refining and fine-tuning their diagnostic instruments. In particular, all these developments aim at increasing the negative predictive value of FNA to improve the selection of patients for diagnostic surgery. These advances involve terminology, the application of next-generation sequencing (NGS) to thyroid FNA, the use of immunocyto- and histochemistry, the development of new sampling techniques and the increasing use of nuclear medicine as well as molecular imaging in the management of patient with a thyroid nodule. Herein, we review the recent advances in thyroid FNA cytology that could be of interest for the "thyroid-care" community, with particular focus on the indeterminate diagnostic category.
Eighty-four patients with choledochocele collected from the world literature and one personal obs... more Eighty-four patients with choledochocele collected from the world literature and one personal observation are reviewed. The main issues regarding clinical presentation, diagnostic work-up, and the treatment of this uncommon lesion are discussed. Abdominal pain was the most common clinical feature (91% of cases), followed by pancreatitis (38%), nausea or vomiting (35%), and jaundice (26%). In addition, associated lithiasis was found in 43% of the cases. Endoscopic retrograde cholangiopancreatography was the most useful diagnostic procedure and resulted in a correct diagnosis in all but one of the patients investigated by this method. Surgical excision of the duodenal luminal portion of the choledochocele was the treatment most commonly used (65% of cases). In recent years, operative endoscopy has also been increasingly used, with good results.
Fine needle aspiration Cytology (FNAC) fulfills a reliable role in the evaluation of thyroid lesi... more Fine needle aspiration Cytology (FNAC) fulfills a reliable role in the evaluation of thyroid lesions. Although the majority of nodules are quite easily diagnosed as benign or malignant, 30% of them represent an indeterminate category whereby the application of ancillary techniques (i.e. immunocytochemistry-ICC and molecular testing) has been encouraged. The search for a specific immunomarker of malignancy sheds light on a huge number of ICC stains although none of them attempt to yield 100% conclusive results. Our aim was to define in a pilot study on thyroid FNAC whether CD56 might be a valid marker also in comparison with HBME-1 and Galectin-3. Inasmuch as this is the largest pilot study using only liquid based cytology (LBC), we selected all the cases only in the categories of benign nodules (BN) and positive for malignancy (PM) for validation purposes. Eighty-five consecutive (including 50 PM and 35 BN) out of 950 thyroid FNACs had surgical follow-up. The ICC panel (HBME-1, Galectin-3 and CD56) was carried out on LBC and histology. All BNs and PMs were histological confirmed. CD56 was negative in 96% of the PM while 68.5% of the BNs showed cytoplasmic positivity for this marker, with an overall high sensitivity (96%) but lower specificity (69%). In specific, our 96% of the PMs did not show any follicular cell with CD56 expression. Different ICC combinations were evaluated showing that the panel made up of CD56 plus HBME-1 and Galectin-3 had the highest sensitivity (98%) and specificity (86%). Our pilot study suggests that CD56 may be a good marker for ruling out PTC and its variants. The low specificity suggests that an immunopanel including also HBME-1 and Galectin-3 could obtain the highest diagnostic accuracy in thyroid lesions. Our results suggest that CD56 may be a feasible additional marker for identifying malignancies also in the FNs and SMs.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1996
We present 131I scintigraphic findings in a patient with insular carcinoma of the thyroid showing... more We present 131I scintigraphic findings in a patient with insular carcinoma of the thyroid showing diffuse abnormal uptake throughout the skeleton. The scintigraphy closely resembled the pattern of [131I]MIBG distribution in children with bone marrow metastases of neuroblastoma. The extent of involvement was underestimated by bone scintigraphy and radiography. Insular carcinoma of the thyroid in the bone marrow was subsequently demonstrated by biopsy. The patient was treated with 242 mCi 131I given in two courses, which led to severe myelosuppression and died as a result of progressive disease and severe pancytopenia 10 mo after initial therapy.
Background Although papillary thyroid microcarcinoma (PTMC) is diagnosed with increasing frequenc... more Background Although papillary thyroid microcarcinoma (PTMC) is diagnosed with increasing frequency, the best therapeutic option and follow-up protocol have not been established yet, especially in the case of incidental diagnosis. We reviewed our series of patients with PTMC to determine risk factors for recurrence in an area where there is a high prevalence of goiter. Methods The medical records of all patients who underwent thyroidectomy with a final pathology report of PTMC between October 2002 and June 2007 were reviewed. PTMC was defined as a papillary thyroid carcinoma 10 mm or less in diameter. Follow-up evaluation was obtained by outpatient consultation and/or telephone interview. Results In a series of 2,220 patients who underwent thyroidectomy for a thyroid carcinoma, 933 had a PTMC. Diagnosis was incidental in 704 patients (75.5%). Upon multivariate analysis, tumor size, nonincidental diagnosis, and neck node metastases at diagnosis were independent risk factors for extracapsular spread (ECS), while ECS, multifocal disease, and number of removed lymph nodes were independent risk factors for lymph node metastases at diagnosis. Follow-up evaluation was completed in 287 patients, 9 (3.1%) of whom experienced recurrence. The number of removed and metastasized nodes at first operation and the length of the follow-up were independent risk factors for recurrent disease. Conclusions Incidental diagnosis of PTMC is frequent in a high prevalence of goiter area. PTMC shows a variable degree of aggressiveness. Management protocols should be based on patient-and tumor-related prognostic factors, as for larger tumors.
We describe our technique of diagnostic lobectomy (DL) and the rationale it is based on. We defin... more We describe our technique of diagnostic lobectomy (DL) and the rationale it is based on. We define DL as a minimally invasive procedure consisting of total lobectomy and isthmusectomy, with preservation of the omolateral recurrent laryngeal nerve and parathyroid glands, but without digital exploration of the contralateral lobe. The fact that re-entry into the previously explored field to complete thyroidectomy increases the risk of complications must be taken into consideration. The subjects were 63 consecutive patients who underwent surgery for unilobar follicular neoplasms of the thyroid gland between January 1997 and December 2002. There were 49 follicular adenomas and 14 carcinomas. In the 14 patients with thyroid cancer, total thyroidectomy was performed within 2 weeks after the first operation in a sterile environment with normal anatomical cleavage plains, avoiding any risk of injury to the laryngeal nerves and parathyroid glands. It is concluded that DL is a safe and suitable surgical procedure for patients with follicular-structured lesions of the thyroid gland.
Oncocytic tumours rarely affect the major salivary glands, accounting for less than 1% of all sal... more Oncocytic tumours rarely affect the major salivary glands, accounting for less than 1% of all salivary-gland tumours. The World Health Organisation classification groups these tumours into three principal types: diffuse oncocytosis, focal adenomatous oncocytic hyperplasia and oncocytoma. Diffuse hyperplastic oncocytosis is the rarest lesion: only six cases have been previously reported in the literature. This condition of putative hyperplastic pathogenesis follows a benign course, whereas oncocytomas may recur after excision. No metastatic dissemination or recurrence of diffuse hyperplastic oncocytosis has been reported. We present and discuss a new case of diffuse hyperplastic oncocytosis of the parotid gland.
Proliferating cell nuclear antigen (PCNA) is one of the cell cycle-related proteins directly invo... more Proliferating cell nuclear antigen (PCNA) is one of the cell cycle-related proteins directly involved in DNA synthesis. It is a marker of cellular proliferation and has been shown to correlate with ploidy and proliferative activity of cells. Its expression has been used to estimate the growth fraction of human cancer and its prognostic value. Pigmented villo-nodular synovitis (PVNS) is characterised by a nodular lesion in the paratendinous synovial tissue or, less frequently, in a joint. Whether PVNS is a neoplastic or inflammatory lesion remains controversial. We have studied immunohistochemical PCNA expression with pc10 monoclonal antibody in 16 paraffin sections, in 16 cases of localised PVNS, or giant cell tumour of tendon sheath. We have found significant correlation between the size of the lesions and PCNA-LI (labelling index).
Dyshormonogenetic goiter (DG) presents a pathological picture characterized by many solid nodular... more Dyshormonogenetic goiter (DG) presents a pathological picture characterized by many solid nodular lesions with different patterns, a peculiar appearance of the surrounding nonnodular thyroid tissue, and the presence of features suspicious for carcinoma. Such features are caused by a high serum level of TSH (thyroid-stimulating hormone) in response to defects in the production of the thyroid hormone. The pathophysiology of
Solitary fibrous tumour (SFT) is a rare tumour principally found in adults in the pleural cavity.... more Solitary fibrous tumour (SFT) is a rare tumour principally found in adults in the pleural cavity. Extrapleural occurrences are rare. Two cases of SFT of the thyroid gland are described in this paper showing their distinctive microscopical architecture, namely ''patternless growth pattern''. It is characterized by a bland spindle-cell proliferation alternating hyper-and hypo-cellular areas, keloidlike hyalinization and a focal hemangiopericytoma-like vascular pattern. Tumour cells revealed a diffuse strong positivity for CD34, CD99, bcl-2 and Vimentin, but negativity for Desmin, EMA, AE1/AE3, SMA, S-100 and CD31 antibodies. The differential diagnosis of thyroid SFT includes different types of spindle cell proliferation, benign and malignant mesenchymal tumours, medullary thyroid carcinoma, fasciitis-like papillary carcinoma, and undifferentiated (anaplastic) carcinoma. However, the morphologic and immunohistochemical findings of SFT are so characteristic that this diagnosis seldom represent a difficulty.
Metastatic involvement of the mediastinal lymph nodes is an extremely uncommon finding in epithel... more Metastatic involvement of the mediastinal lymph nodes is an extremely uncommon finding in epithelial ovarian cancers. A 63-year-old woman was admitted to hospital for dyspnoea due to an anterior mediastinal mass. The surgical biopsy showed a 6-cm metastatic lymph node with a papillary pattern, scattered psammomas and immunoreactivity for WT1, Cytokeratin 7, EMA and negative for E-cadherin, GCFDP-15, Thyroglobulin, Cytokeratin 20, Cytokeratin 5/6, CEA, Vimentin, Calretinin, TTF1. After 20 months a follow-up CT identified an ovarian mass with the same histological pattern and immunoreactivity of the mediastinal nodule. Immunohistochemistry, especially WT1, is useful in assessing the ovarian origin of an unusual metastasis particularly if it is the first presentation of the disease.
Objective: To report on a patient with endomyometrioma with atypias and to review the literature.... more Objective: To report on a patient with endomyometrioma with atypias and to review the literature. Design: Case report and literature review. Setting: Clinical and pathologic. Patient(s): A 33-year-old nulliparous woman with right flank pain and infertility. Main Outcome Measure(s): Accuracy of diagnosis, hypotheses on endomyometrioma pathogenesis. Result(s): A 33-year-old woman with an 8-cm right ovarian mass is reported. An extensive review of the literature on this rare disease revealed only nine well-documented cases with different views on pathogenesis. The final diagnosis required an accurate sampling and the aid of immunohistochemical markers. Conclusion(s): Endomyometrioma is an extremely rare entity. None of the previous cases showed cytologic atypias. The finding of atypias, in analogy with endometriosis, suggests the müllerian metaplastic theory. (Fertil Steril Ò 2007;88:1438.e15-7.
The Chernobyl accident was followed by a large increase in the incidence of thyroid carcinoma in ... more The Chernobyl accident was followed by a large increase in the incidence of thyroid carcinoma in the areas exposed to high levels of fallout. The Chernobyl Tumor Bank was set up in 1998 to make tumours available for study internationally, and a pathology panel reviewed all the tumours and established an agreed diagnosis. The thyroid tumours that were discovered after the Chernobyl nuclear accident were virtually all (95%) of the papillary carcinoma type. Rare examples of other tumour types were identified. Within the papillary group, several subtypes were noted, including classical or usual type, follicular variant, solid variant and mixed patterns Diffuse sclerosis variant, cribriform/morular type and Warthin-like variant were rare. No tall cell or columnar cell variants were identified. The tumours examined by the Pathology Panel of the Chernobyl Tumor Bank constitute a large representative sample (estimated at about 50%) of the tumours that developed in this population. This overview describes the method adopted by the panel and the different diagnostic categories adopted; illustrates the pathology of these neoplasms; compares the pathological characteristics of the early lesions with those identified after long latency periods and the institution of screening programmes and outlines the possible associated causes for the various morphological patterns seen.
FOXA1 is a mammalian endodermal transcription factor belonging to the human forkhead box gene fam... more FOXA1 is a mammalian endodermal transcription factor belonging to the human forkhead box gene family that plays a role in certain tumor types. Here, we investigated the potential role of FOXA1 in human thyroid carcinomas. We examined the level of FOXA1 expression and gene copy number by immunohistochemistry and fluorescence in situ hybridization, respectively, in a cohort of benign and malignant thyroid tumors. In addition, we examined the role of FOXA1 in the proliferation of an undifferentiated thyroid carcinoma cell line by short hairpin RNA-mediated silencing. We show that FOXA1 is overexpressed in human anaplastic thyroid carcinomas (ATC). In addition, we identify FOXA1 DNA copy number gain within the 14q21.1 locus in both an ATC cell line and human ATC cases. Silencing of FOXA1 in an ATC cell line causes G(1) growth arrest and reduction of cell proliferation. Moreover, we observe a potential link between FOXA1 and the cell cycle machinery by identifying p27(kip1) up-regulation on FOXA1 silencing. FOXA1 is overexpressed in aggressive thyroid cancers and involved in cell cycle progression in an ATC cell line. Therefore, FOXA1 may be an important oncogene in thyroid tumorigenesis and a potential new therapeutic target for the treatment of anaplastic thyroid cancers.
Fine needle aspiration cytology represents the most important tool in the diagnosis of thyroid no... more Fine needle aspiration cytology represents the most important tool in the diagnosis of thyroid nodules, mostly in discriminating malignant from benign lesions. The diagnosis of medullary thyroid carcinoma (MTC) may present some problems related to its deceptive morphologic picture. This diagnosis may be supported by immunocytochemistry (ICC), which may be difficult to carry out on the conventional smears. The diagnostic efficacy of ICC for the diagnosis of MTC with respect to other thyroid neoplasms on slides processed by thin-layer cytology (TLC) is evaluated. In the period between January 2002 and December 2005, 8,200 FNAB were processed. ICC on TLC slides was required in 33 cases. Conventional smears were fixed in ethanol, whereas TLC slides were processed with the Thin Prep 2000 method. All slides were then stained with Papanicolaou. In all cases where MTC was morphologically suspected, ICC for calcitonin, monoclonal carcinoembryonic antigen, and thyroglobulin was carried out only on TLC slides. Thirty-three thyroid cytologic cases had ICC on the TLC slides, including 22 follicular proliferations and 11 malignant lesions. The application of ICC on TLC was conclusive in 32 cases and inconclusive in 1 case. Twenty cases underwent surgery. No false-positive and false-negative cases were found. Sensitivity and specificity were 100%, and the overall diagnostic accuracy was 100%. ICC can be successfully applied on TLC slides. The combined results of morphology and a small immunopanel including thyroglobulin, calcitonin, and carcinoembryonic antigen yields a 100% diagnostic efficacy for MTC. Fine needle aspiration cytology is an excellent technique for diagnosing malignant neoplasms of the thyroid, especially those derived from the follicular cells. A correct preoperative diagnosis of C-cell-derived tumors (MTC), which is essential for both the surgical approach to the primary tumor and the management of the patient, should rely not only on the morphologic picture but also on the immunocytochemical yielding using an immunopanel, which is particularly satisfactory on the TLC slides.
Myopericytoma (MPC) is a rare tumor with perivascular proliferation of pluripotent stem-cell-like... more Myopericytoma (MPC) is a rare tumor with perivascular proliferation of pluripotent stem-cell-like pericytes. Although indolent, MPC may be locally aggressive with recurrent disease. The pathogenesis and diagnostic biomarkers of MPC are poorly understood. We discovered that 15% of benign MPCs (thyroid, skin; 3 of 20 samples) harbored BRAF(WT/V600E); 33.3% (1 of 3 samples) of BRAF(WT/V600E)-MPCs were multifocal/infiltrative/recurrent. Patient-MPC and primary MPC cells harbored BRAF(WT/V600E), were clonal and expressed pericytic-differentiation biomarkers crucial for its microenvironment. BRAF(WT/V600E)-positive thyroid MPC primary cells triggered in vitro (8.8-fold increase) and in vivo (3.6-fold increase) angiogenesis. Anti-BRAF(V600E) therapy with vemurafenib disrupted angiogenic and metabolic properties (~3-fold decrease) with down-regulation (~2.2-fold decrease) of some extracellular-matrix (ECM) factors and ECM-associated long non-coding RNA (LincRNA) expression, with no effects ...
Thyroid fine-needle aspiration (FNA) cytology is a fast growing field. One of the most developing... more Thyroid fine-needle aspiration (FNA) cytology is a fast growing field. One of the most developing areas is represented by molecular tests applied to cytological material. Patients that could benefit the most from these tests are those that have been diagnosed as "indeterminate" on FNA. They could be better stratified in terms of malignancy risk and thus oriented with more confidence to the appropriate management. Taking in consideration this need to improve and keep high the yield of thyroid FNA, professionals from various fields (i.e. molecular biologists, endocrinologists, nuclear medicine physicians and radiologists) are refining and fine-tuning their diagnostic instruments. In particular, all these developments aim at increasing the negative predictive value of FNA to improve the selection of patients for diagnostic surgery. These advances involve terminology, the application of next-generation sequencing (NGS) to thyroid FNA, the use of immunocyto- and histochemistry, the development of new sampling techniques and the increasing use of nuclear medicine as well as molecular imaging in the management of patient with a thyroid nodule. Herein, we review the recent advances in thyroid FNA cytology that could be of interest for the "thyroid-care" community, with particular focus on the indeterminate diagnostic category.
Eighty-four patients with choledochocele collected from the world literature and one personal obs... more Eighty-four patients with choledochocele collected from the world literature and one personal observation are reviewed. The main issues regarding clinical presentation, diagnostic work-up, and the treatment of this uncommon lesion are discussed. Abdominal pain was the most common clinical feature (91% of cases), followed by pancreatitis (38%), nausea or vomiting (35%), and jaundice (26%). In addition, associated lithiasis was found in 43% of the cases. Endoscopic retrograde cholangiopancreatography was the most useful diagnostic procedure and resulted in a correct diagnosis in all but one of the patients investigated by this method. Surgical excision of the duodenal luminal portion of the choledochocele was the treatment most commonly used (65% of cases). In recent years, operative endoscopy has also been increasingly used, with good results.
Fine needle aspiration Cytology (FNAC) fulfills a reliable role in the evaluation of thyroid lesi... more Fine needle aspiration Cytology (FNAC) fulfills a reliable role in the evaluation of thyroid lesions. Although the majority of nodules are quite easily diagnosed as benign or malignant, 30% of them represent an indeterminate category whereby the application of ancillary techniques (i.e. immunocytochemistry-ICC and molecular testing) has been encouraged. The search for a specific immunomarker of malignancy sheds light on a huge number of ICC stains although none of them attempt to yield 100% conclusive results. Our aim was to define in a pilot study on thyroid FNAC whether CD56 might be a valid marker also in comparison with HBME-1 and Galectin-3. Inasmuch as this is the largest pilot study using only liquid based cytology (LBC), we selected all the cases only in the categories of benign nodules (BN) and positive for malignancy (PM) for validation purposes. Eighty-five consecutive (including 50 PM and 35 BN) out of 950 thyroid FNACs had surgical follow-up. The ICC panel (HBME-1, Galectin-3 and CD56) was carried out on LBC and histology. All BNs and PMs were histological confirmed. CD56 was negative in 96% of the PM while 68.5% of the BNs showed cytoplasmic positivity for this marker, with an overall high sensitivity (96%) but lower specificity (69%). In specific, our 96% of the PMs did not show any follicular cell with CD56 expression. Different ICC combinations were evaluated showing that the panel made up of CD56 plus HBME-1 and Galectin-3 had the highest sensitivity (98%) and specificity (86%). Our pilot study suggests that CD56 may be a good marker for ruling out PTC and its variants. The low specificity suggests that an immunopanel including also HBME-1 and Galectin-3 could obtain the highest diagnostic accuracy in thyroid lesions. Our results suggest that CD56 may be a feasible additional marker for identifying malignancies also in the FNs and SMs.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1996
We present 131I scintigraphic findings in a patient with insular carcinoma of the thyroid showing... more We present 131I scintigraphic findings in a patient with insular carcinoma of the thyroid showing diffuse abnormal uptake throughout the skeleton. The scintigraphy closely resembled the pattern of [131I]MIBG distribution in children with bone marrow metastases of neuroblastoma. The extent of involvement was underestimated by bone scintigraphy and radiography. Insular carcinoma of the thyroid in the bone marrow was subsequently demonstrated by biopsy. The patient was treated with 242 mCi 131I given in two courses, which led to severe myelosuppression and died as a result of progressive disease and severe pancytopenia 10 mo after initial therapy.
Background Although papillary thyroid microcarcinoma (PTMC) is diagnosed with increasing frequenc... more Background Although papillary thyroid microcarcinoma (PTMC) is diagnosed with increasing frequency, the best therapeutic option and follow-up protocol have not been established yet, especially in the case of incidental diagnosis. We reviewed our series of patients with PTMC to determine risk factors for recurrence in an area where there is a high prevalence of goiter. Methods The medical records of all patients who underwent thyroidectomy with a final pathology report of PTMC between October 2002 and June 2007 were reviewed. PTMC was defined as a papillary thyroid carcinoma 10 mm or less in diameter. Follow-up evaluation was obtained by outpatient consultation and/or telephone interview. Results In a series of 2,220 patients who underwent thyroidectomy for a thyroid carcinoma, 933 had a PTMC. Diagnosis was incidental in 704 patients (75.5%). Upon multivariate analysis, tumor size, nonincidental diagnosis, and neck node metastases at diagnosis were independent risk factors for extracapsular spread (ECS), while ECS, multifocal disease, and number of removed lymph nodes were independent risk factors for lymph node metastases at diagnosis. Follow-up evaluation was completed in 287 patients, 9 (3.1%) of whom experienced recurrence. The number of removed and metastasized nodes at first operation and the length of the follow-up were independent risk factors for recurrent disease. Conclusions Incidental diagnosis of PTMC is frequent in a high prevalence of goiter area. PTMC shows a variable degree of aggressiveness. Management protocols should be based on patient-and tumor-related prognostic factors, as for larger tumors.
We describe our technique of diagnostic lobectomy (DL) and the rationale it is based on. We defin... more We describe our technique of diagnostic lobectomy (DL) and the rationale it is based on. We define DL as a minimally invasive procedure consisting of total lobectomy and isthmusectomy, with preservation of the omolateral recurrent laryngeal nerve and parathyroid glands, but without digital exploration of the contralateral lobe. The fact that re-entry into the previously explored field to complete thyroidectomy increases the risk of complications must be taken into consideration. The subjects were 63 consecutive patients who underwent surgery for unilobar follicular neoplasms of the thyroid gland between January 1997 and December 2002. There were 49 follicular adenomas and 14 carcinomas. In the 14 patients with thyroid cancer, total thyroidectomy was performed within 2 weeks after the first operation in a sterile environment with normal anatomical cleavage plains, avoiding any risk of injury to the laryngeal nerves and parathyroid glands. It is concluded that DL is a safe and suitable surgical procedure for patients with follicular-structured lesions of the thyroid gland.
Oncocytic tumours rarely affect the major salivary glands, accounting for less than 1% of all sal... more Oncocytic tumours rarely affect the major salivary glands, accounting for less than 1% of all salivary-gland tumours. The World Health Organisation classification groups these tumours into three principal types: diffuse oncocytosis, focal adenomatous oncocytic hyperplasia and oncocytoma. Diffuse hyperplastic oncocytosis is the rarest lesion: only six cases have been previously reported in the literature. This condition of putative hyperplastic pathogenesis follows a benign course, whereas oncocytomas may recur after excision. No metastatic dissemination or recurrence of diffuse hyperplastic oncocytosis has been reported. We present and discuss a new case of diffuse hyperplastic oncocytosis of the parotid gland.
Proliferating cell nuclear antigen (PCNA) is one of the cell cycle-related proteins directly invo... more Proliferating cell nuclear antigen (PCNA) is one of the cell cycle-related proteins directly involved in DNA synthesis. It is a marker of cellular proliferation and has been shown to correlate with ploidy and proliferative activity of cells. Its expression has been used to estimate the growth fraction of human cancer and its prognostic value. Pigmented villo-nodular synovitis (PVNS) is characterised by a nodular lesion in the paratendinous synovial tissue or, less frequently, in a joint. Whether PVNS is a neoplastic or inflammatory lesion remains controversial. We have studied immunohistochemical PCNA expression with pc10 monoclonal antibody in 16 paraffin sections, in 16 cases of localised PVNS, or giant cell tumour of tendon sheath. We have found significant correlation between the size of the lesions and PCNA-LI (labelling index).
Dyshormonogenetic goiter (DG) presents a pathological picture characterized by many solid nodular... more Dyshormonogenetic goiter (DG) presents a pathological picture characterized by many solid nodular lesions with different patterns, a peculiar appearance of the surrounding nonnodular thyroid tissue, and the presence of features suspicious for carcinoma. Such features are caused by a high serum level of TSH (thyroid-stimulating hormone) in response to defects in the production of the thyroid hormone. The pathophysiology of
Solitary fibrous tumour (SFT) is a rare tumour principally found in adults in the pleural cavity.... more Solitary fibrous tumour (SFT) is a rare tumour principally found in adults in the pleural cavity. Extrapleural occurrences are rare. Two cases of SFT of the thyroid gland are described in this paper showing their distinctive microscopical architecture, namely ''patternless growth pattern''. It is characterized by a bland spindle-cell proliferation alternating hyper-and hypo-cellular areas, keloidlike hyalinization and a focal hemangiopericytoma-like vascular pattern. Tumour cells revealed a diffuse strong positivity for CD34, CD99, bcl-2 and Vimentin, but negativity for Desmin, EMA, AE1/AE3, SMA, S-100 and CD31 antibodies. The differential diagnosis of thyroid SFT includes different types of spindle cell proliferation, benign and malignant mesenchymal tumours, medullary thyroid carcinoma, fasciitis-like papillary carcinoma, and undifferentiated (anaplastic) carcinoma. However, the morphologic and immunohistochemical findings of SFT are so characteristic that this diagnosis seldom represent a difficulty.
Metastatic involvement of the mediastinal lymph nodes is an extremely uncommon finding in epithel... more Metastatic involvement of the mediastinal lymph nodes is an extremely uncommon finding in epithelial ovarian cancers. A 63-year-old woman was admitted to hospital for dyspnoea due to an anterior mediastinal mass. The surgical biopsy showed a 6-cm metastatic lymph node with a papillary pattern, scattered psammomas and immunoreactivity for WT1, Cytokeratin 7, EMA and negative for E-cadherin, GCFDP-15, Thyroglobulin, Cytokeratin 20, Cytokeratin 5/6, CEA, Vimentin, Calretinin, TTF1. After 20 months a follow-up CT identified an ovarian mass with the same histological pattern and immunoreactivity of the mediastinal nodule. Immunohistochemistry, especially WT1, is useful in assessing the ovarian origin of an unusual metastasis particularly if it is the first presentation of the disease.
Objective: To report on a patient with endomyometrioma with atypias and to review the literature.... more Objective: To report on a patient with endomyometrioma with atypias and to review the literature. Design: Case report and literature review. Setting: Clinical and pathologic. Patient(s): A 33-year-old nulliparous woman with right flank pain and infertility. Main Outcome Measure(s): Accuracy of diagnosis, hypotheses on endomyometrioma pathogenesis. Result(s): A 33-year-old woman with an 8-cm right ovarian mass is reported. An extensive review of the literature on this rare disease revealed only nine well-documented cases with different views on pathogenesis. The final diagnosis required an accurate sampling and the aid of immunohistochemical markers. Conclusion(s): Endomyometrioma is an extremely rare entity. None of the previous cases showed cytologic atypias. The finding of atypias, in analogy with endometriosis, suggests the müllerian metaplastic theory. (Fertil Steril Ò 2007;88:1438.e15-7.
The Chernobyl accident was followed by a large increase in the incidence of thyroid carcinoma in ... more The Chernobyl accident was followed by a large increase in the incidence of thyroid carcinoma in the areas exposed to high levels of fallout. The Chernobyl Tumor Bank was set up in 1998 to make tumours available for study internationally, and a pathology panel reviewed all the tumours and established an agreed diagnosis. The thyroid tumours that were discovered after the Chernobyl nuclear accident were virtually all (95%) of the papillary carcinoma type. Rare examples of other tumour types were identified. Within the papillary group, several subtypes were noted, including classical or usual type, follicular variant, solid variant and mixed patterns Diffuse sclerosis variant, cribriform/morular type and Warthin-like variant were rare. No tall cell or columnar cell variants were identified. The tumours examined by the Pathology Panel of the Chernobyl Tumor Bank constitute a large representative sample (estimated at about 50%) of the tumours that developed in this population. This overview describes the method adopted by the panel and the different diagnostic categories adopted; illustrates the pathology of these neoplasms; compares the pathological characteristics of the early lesions with those identified after long latency periods and the institution of screening programmes and outlines the possible associated causes for the various morphological patterns seen.
FOXA1 is a mammalian endodermal transcription factor belonging to the human forkhead box gene fam... more FOXA1 is a mammalian endodermal transcription factor belonging to the human forkhead box gene family that plays a role in certain tumor types. Here, we investigated the potential role of FOXA1 in human thyroid carcinomas. We examined the level of FOXA1 expression and gene copy number by immunohistochemistry and fluorescence in situ hybridization, respectively, in a cohort of benign and malignant thyroid tumors. In addition, we examined the role of FOXA1 in the proliferation of an undifferentiated thyroid carcinoma cell line by short hairpin RNA-mediated silencing. We show that FOXA1 is overexpressed in human anaplastic thyroid carcinomas (ATC). In addition, we identify FOXA1 DNA copy number gain within the 14q21.1 locus in both an ATC cell line and human ATC cases. Silencing of FOXA1 in an ATC cell line causes G(1) growth arrest and reduction of cell proliferation. Moreover, we observe a potential link between FOXA1 and the cell cycle machinery by identifying p27(kip1) up-regulation on FOXA1 silencing. FOXA1 is overexpressed in aggressive thyroid cancers and involved in cell cycle progression in an ATC cell line. Therefore, FOXA1 may be an important oncogene in thyroid tumorigenesis and a potential new therapeutic target for the treatment of anaplastic thyroid cancers.
Fine needle aspiration cytology represents the most important tool in the diagnosis of thyroid no... more Fine needle aspiration cytology represents the most important tool in the diagnosis of thyroid nodules, mostly in discriminating malignant from benign lesions. The diagnosis of medullary thyroid carcinoma (MTC) may present some problems related to its deceptive morphologic picture. This diagnosis may be supported by immunocytochemistry (ICC), which may be difficult to carry out on the conventional smears. The diagnostic efficacy of ICC for the diagnosis of MTC with respect to other thyroid neoplasms on slides processed by thin-layer cytology (TLC) is evaluated. In the period between January 2002 and December 2005, 8,200 FNAB were processed. ICC on TLC slides was required in 33 cases. Conventional smears were fixed in ethanol, whereas TLC slides were processed with the Thin Prep 2000 method. All slides were then stained with Papanicolaou. In all cases where MTC was morphologically suspected, ICC for calcitonin, monoclonal carcinoembryonic antigen, and thyroglobulin was carried out only on TLC slides. Thirty-three thyroid cytologic cases had ICC on the TLC slides, including 22 follicular proliferations and 11 malignant lesions. The application of ICC on TLC was conclusive in 32 cases and inconclusive in 1 case. Twenty cases underwent surgery. No false-positive and false-negative cases were found. Sensitivity and specificity were 100%, and the overall diagnostic accuracy was 100%. ICC can be successfully applied on TLC slides. The combined results of morphology and a small immunopanel including thyroglobulin, calcitonin, and carcinoembryonic antigen yields a 100% diagnostic efficacy for MTC. Fine needle aspiration cytology is an excellent technique for diagnosing malignant neoplasms of the thyroid, especially those derived from the follicular cells. A correct preoperative diagnosis of C-cell-derived tumors (MTC), which is essential for both the surgical approach to the primary tumor and the management of the patient, should rely not only on the morphologic picture but also on the immunocytochemical yielding using an immunopanel, which is particularly satisfactory on the TLC slides.
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Papers by Guido Fadda