Francesca Maletta - Academia.edu (original) (raw)
Papers by Francesca Maletta
Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie
Irregularity in the nuclear shape, with extensive folds and invaginations of the nuclear membrane... more Irregularity in the nuclear shape, with extensive folds and invaginations of the nuclear membrane (NM), remain the basic diagnostic feature of papillary thyroid carcinoma (PTC). The biological reasons for these irregularities are obscure, but evidence has been presented that they might be linked to RET÷PTC gene translocation. In the present study, we have investigated the hypothesis that the NM irregularities in PTC might be linked to alterations in the expression of lamin B receptor (LBR), a component of the inner NM responsible for the distribution of Lamin B and associated chromatin. Fisher AH et al. already reported on the lack of LBR in PTC, a finding in contrast with the observation that a reduced expression of LBR because of gene mutation is responsible for the lack of nuclear segmentation of granulocytes in Pelger-Huët anomaly. In the present study, we confirmed the lack of immunohistochemical staining for LBR in PTC nuclei, in contrast to a positive staining in intestinal e...
Digestive and Liver Disease, 2015
The diagnosis of inflammatory bowel disease can be challenging and requires the efforts of a mult... more The diagnosis of inflammatory bowel disease can be challenging and requires the efforts of a multidisciplinary team. We performed a retrospective analysis with the aim of evaluating the adequacy of the prerequisites for arriving at an accurate histological diagnosis. The following parameters were considered as prerequisites for a diagnosis of inflammatory bowel disease: clinical and endoscopic data; proper sampling and handling of biopsies; and elementary microscopic lesions. We collected 345 cases from 13 centres. The date of onset and treatment were available for 13% and 16% of the cases, respectively. Endoscopy information was accessible for 77% of the cases. Endoscopic mapping was completed in 13% of the cases. In no cases were the biopsies oriented on acetate strips. The diagnosis was conclusive in 47% of the cases. Activity, epithelial disruption and crypt distortion were described in 35% of the reports with a conclusive diagnosis. Our study showed that the diagnostic prerequisites were widely unfulfilled, although approximately half of the diagnoses were conclusive for inflammatory bowel disease. Thus, in our assessment of clinical practice: (1) clinicians seldom provide suitable clinical and/or endoscopic information for a histological diagnosis and (2) histopathological diagnoses of inflammatory bowel disease are often not supported by morphology.
Cancer Cytopathology, 2014
The triage of human papillomavirus (HPV)-positive women is needed to avoid overreferral to colpos... more The triage of human papillomavirus (HPV)-positive women is needed to avoid overreferral to colposcopy. p16INK4a immunostaining is an efficient triage method. p16INK4a/Ki-67 dual staining was introduced mainly to increase reproducibility and specificity compared with stand-alone p16INK4a staining. Within a pilot project, HPV-positive women were referred to colposcopy if cytology was abnormal or unsatisfactory or HPV testing was still positive after 1 year. For 500 consecutive women, a slide obtained during colposcopy was immunostained for p16INK4a/Ki-67 and independently interpreted by 7 readers without previous experience with dual staining. Four of these readers were experts in cervical pathology and 3 were not. Kappa values for multiple raters, sensitivity, and specificity for cervical intraepithelial neoplasia type 2-positive histology were computed. Because women with normal cytology were underrepresented, estimates for all HPV-positive women were obtained as weighted means of cytology-specific estimates. The overall kappa for HPV-positive women was 0.70 (95% confidence interval [95% CI], 0.60-0.77). Kappa values were not found to be significantly different between expert and nonexpert readers with regard to cervical cytology but were significantly increased (P =. 0066) after consensus discussion. The overall specificity estimate for HPV-positive women was 64.0% (95% CI, 57.4%-70.2%): 66.7% (95% CI, 59.8%-73.0%) for experts and 60.5% (95% CI, 59.8%-73.0%) for nonexperts. Among women with abnormal cytology, the sensitivity was 85.5% (95% CI, 77.9%-90.8%): 85.8% (95% CI, 77.9%-91.2%) for experts and 85.1% (95% CI, 76.6%-90.9%) for nonexperts. p16INK4a/Ki-67 immunostaining demonstrated good reproducibility and specificity when triaging HPV-positive women. Dual-staining interpretation can be performed, after short training, even by staff who are not experts in cervical cytology. This allows HPV-based screening with triage to be performed in settings in which such expert staff is not available. Cancer (Cancer Cytopathol) 2014. © 2014 American Cancer Society.
Variation in both nuclear shape and size ("pleom... more Variation in both nuclear shape and size ("pleomorphism"), coupled with changes in chromatin amount and distribution, remains the basic criteria for microscopy in a cytologic diagnosis of cancer. The biological determinants of nuclear shape irregularities are not clarified, so, rather than on the genesis of nuclear irregularities, we here focus our attention on a descriptive analysis of nuclear pleomorphism. We keep in mind that evaluation of nuclear shape as currently practiced in routine preparations is improper because it is indirectly based on the distribution of DNA as revealed by the affinity for basic dyes. Therefore, over the last years we have been using as criteria morphological features of nuclei of thyroid and breast carcinomas as determined by immunofluorescence, in situ hybridization, and 3D reconstruction. We have translated this approach to routine diagnostic pathology on tissue sections by employing immunoperoxidase staining for emerin. Direct detection of nuclear envelope irregularities by tagging nuclear membrane proteins such as lamin B and emerin has resulted in a more objective definition of the shape of the nucleus. In this review we discuss in detail methodological issues as well as diagnostic and prognostic implications provided by decoration/staining of the nuclear envelope in both thyroid and breast cancer, thus demonstrating how much it matters "to be in the right shape" when dealing with pathological diagnosis of cancer.
The primary objectives of this study on carcinomas with equivocal HER2 expression were to assess ... more The primary objectives of this study on carcinomas with equivocal HER2 expression were to assess the impact of distinct recommendations with regard to identifying patients eligible for anti-HER2 agents by fluorescence in situ hybridization (FISH) and to elucidate whether multiplex ligation-dependent probe amplification (MLPA) may be of support in assessing HER2 gene status. A cohort of 957 immunohistochemistry-evaluated HER2-equivocal cases was analyzed by dual-color FISH. The results were assessed according to U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines and American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) 2007 and 2013 guidelines for dual- and single-signal in situ hybridization (ISH) assays. A subgroup of 112 cases was subjected to MLPA. HER2 amplification varied from 15% (ASCO/CAP 2007 HER2/CEP17 ratio) to 29.5% (FDA/EMA HER2 copy number). According to the ASCO/CAP 2013 interpretation of the dual-signal HER2 assay, ISH-positive carcinomas accounted for 19.7%. In contrast with the ASCO/CAP 2007 ratio, this approach labeled as positive all 32 cases (3.34%) with a HER2/CEP17 ratio <2 and an average HER2 copy number ≥6.0 signals per cell. In contrast, only one case showing a HER2 copy number <4 but a ratio ≥2 was diagnosed as positive. MLPA data correlated poorly with FISH results because of the presence of heterogeneous HER2 amplification in 33.9% of all amplified carcinomas; however, MLPA ruled out HER2 amplification in 75% of ISH-evaluated HER2-equivocal carcinomas. The ASCO/CAP 2013 guidelines seem to improve the identification of HER2-positive carcinomas. Polymerase chain reaction-based methods such as MLPA can be of help, provided that heterogeneous amplification has been ruled out by ISH.
Virchows Archiv, 2010
Decoration of the nuclear membrane by emerin staining enhances detection of nuclear irregularitie... more Decoration of the nuclear membrane by emerin staining enhances detection of nuclear irregularities typical of papillary thyroid carcinoma (PTC). Our study aims to verify whether staining with emerin is a helpful diagnostic marker in fine-needle aspiration (FNA) cytology. We first designed a prospective study on smears, Thin Prep, and cell block specimens to prove the feasibility of the procedure; subsequently, we designed a retrospective study of 78 FNA cell blocks from cases that, after surgery, turned out to be either benign (34 cases) or malignant lesions (44, of which 31 PTC). From each sample, we obtained two slides, one stained with hematoxylin and eosin (H&E) and the other with emerin. In cases classified as Thy3, HBME-1 and galectin 3 (Gal3) stains had also been performed. Two blinded observers made the judgment concerning Thy categories (as proposed by the British Thyroid Association), first on H&E, then on emerin, HBME-1, and Gal3 stained slides. On cytological preparation, emerin staining represents an effective tool for the detection of nuclear irregularities, allowing for the identification of cases of PTC. In Thy3 cases, emerin staining's sensitivity and specificity (64% and 96%) proved higher than HBME-1's (60% and 88%) and Gal3's (61% and 68%). In conclusion, the immunohistochemical definition of the nuclear membrane, as determined by emerin stain, is a useful tool in the cytological diagnosis of thyroid lesions and can help to solve inconclusive cases by highlighting nuclear irregularities typical of PTC.
Modern Pathology, 2011
Merkel cell carcinoma of the skin is a malignant neuroendocrine tumour, whose prognostic criteria... more Merkel cell carcinoma of the skin is a malignant neuroendocrine tumour, whose prognostic criteria are a matter of dispute. Specifically, no predictor is presently available in stage I-II tumours. We collected clinical and follow-up data from 70 Merkel cell carcinomas of the skin. The same cases were studied for p63 expression by immunohistochemistry, by reverse-transcription PCR (RT-PCR) and TP63 gene status by FISH and for presence of Merkel cell polyomavirus by PCR. Stage emerged as a significant prognostic parameter (P=0.008). p63 expression, detected in 61% (43/70) of cases by immunohistochemistry, was associated with both decreased overall survival (P<0.0001) and disease-free survival (P<0.0001). Variable expression patterns of the different p63 isoforms were found only in cases immunoreactive for p63. In these latter lesions, at least one of the N-terminal p63 isoforms was detected and TAp63α was the most frequently expressed isoform. TP63 gene amplification was observed by FISH in only one case. Presence of Merkel cell polyomavirus DNA sequences was detected in 86% (60/70) of Merkel cell carcinomas and did not emerge as a significant prognostic parameter. Merkel cell carcinoma cases at low stage (stage I-II) represented over half (40/70 cases, 57%) of cases, and the clinical course was uneventful in 25 of 40 cases while 15 cases died of tumour (10/40 cases) within 34 months or were alive with disease (5/40 cases) within 20 months. Interestingly, a very strict correlation was found between evolution and p63 expression (P<0.0001). The present data indicate that p63 expression is associated with a worse prognosis in patients with Merkel cell carcinoma, and in localised tumours it represents the single independent predictor of clinical evolution.
Head & Neck Surgery, 1987
Chondrosarcoma of the head and neck region is a rarely encountered tumor. Aggressive surgical exc... more Chondrosarcoma of the head and neck region is a rarely encountered tumor. Aggressive surgical excision offers the best chance for cure. In our case, combined diagnostic techniques consisting of fine needle aspiration (FNA), computed tomography (CT), and magnetic resonance imaging (MRI) made an accurate preoperative assessment possible and greatly influenced the treatment provided.
Digestive and Liver Disease, 2011
Diagnostic Cytopathology, 2014
Recent reports indicate that hobnail papillary thyroid carcinoma (HPTC) is a rare, but very aggre... more Recent reports indicate that hobnail papillary thyroid carcinoma (HPTC) is a rare, but very aggressive variant of papillary thyroid carcinoma. The authors describe the cytological features of five HPTC on fine-needle aspiration biopsies (FNAB). Moreover, their immunophenotype and the presence of B-RAF mutation by pyrosequencing were investigated. The patients' (three females and two males) age ranged from 27 to 86 (mean 65) years. Tumor size ranged from 2 to 9 cm (mean 4.2 cm). FNAB were highly cellular with a bloody background and scant colloid. The cells were arranged in papillary-like clusters or in micropapillary groups. The cell population consisted of medium-sized cells with "tear-drop" cytoplasm, apically placed nuclei that produced a surface bulge leading to a hobnail appearance. At higher magnification, nuclei showed variable degrees of atypia, occasional pink intranuclear pseudoinclusions, and grooves. Nuclear stratification and atypical mitotic figures were usually present. Immunocytochemistry revealed positive staining for thyroglobulin, thyroid transcriptor factor-1, Hector Battifora Mesothelial Antigen-1, partial loss of E-cadherin expression, and nuclear expression of p53 protein. B-RAF mutation was present in three out of five cytological cases. Immunohistochemical and molecular results were confirmed on histological sections. Recognizing the unique cytological features of HPTC should help to avoid misdiagnosis of this rare variant. Diagn. Cytopathol. 2014;42:78-84. V C 2013 Wiley Periodicals, Inc.
JNCI Monographs, 2015
Neoadjuvant therapy is increasingly being used in the management of breast cancer patients and, s... more Neoadjuvant therapy is increasingly being used in the management of breast cancer patients and, since comprehensive specimen handling and precise histological reporting is essential to assess the degree of response to therapy, histopathologists are acknowledged to play a key role in this multidisciplinary setting. However, as a matter of fact, only minimal guidelines for specimen handling are on record. This means that in every day routine practice it is not uncommon for oncologists to deal with pathology reports where important parameters are missing (such as formal comments about therapy response). According to the latest American Joint Committee on Cancer (AJCC) staging classification, posttreatment size of residual disease (ypT) should be estimated based on the best combination of imaging, gross and microscopic histological findings. Therefore, pathologists should ideally be provided with clinical and radiological information before proceeding with careful grossing. During the cut-up, large sections or extensive mapping of samples submitted to microscopic evaluation should be carried out to reconstruct the disease extent: this is particularly crucial when the lesion is unapparent both at imaging and at macroscopic observation. Histopathological reports cannot preclude from mandatory information about the presence of residual invasive carcinoma, such as histotyping, staging (ypTNM), reevaluation of prognostic and predictive factors, and categorization of degree of response according to dedicated classification systems (performed by comparing pretreatment biopsies with surgical specimens). In this review we will analyze the critical issues in such an assessment and we will provide a pragmatic approach with the intent to aim at the "perfect" pathology report.
Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie
Irregularity in the nuclear shape, with extensive folds and invaginations of the nuclear membrane... more Irregularity in the nuclear shape, with extensive folds and invaginations of the nuclear membrane (NM), remain the basic diagnostic feature of papillary thyroid carcinoma (PTC). The biological reasons for these irregularities are obscure, but evidence has been presented that they might be linked to RET÷PTC gene translocation. In the present study, we have investigated the hypothesis that the NM irregularities in PTC might be linked to alterations in the expression of lamin B receptor (LBR), a component of the inner NM responsible for the distribution of Lamin B and associated chromatin. Fisher AH et al. already reported on the lack of LBR in PTC, a finding in contrast with the observation that a reduced expression of LBR because of gene mutation is responsible for the lack of nuclear segmentation of granulocytes in Pelger-Huët anomaly. In the present study, we confirmed the lack of immunohistochemical staining for LBR in PTC nuclei, in contrast to a positive staining in intestinal e...
Digestive and Liver Disease, 2015
The diagnosis of inflammatory bowel disease can be challenging and requires the efforts of a mult... more The diagnosis of inflammatory bowel disease can be challenging and requires the efforts of a multidisciplinary team. We performed a retrospective analysis with the aim of evaluating the adequacy of the prerequisites for arriving at an accurate histological diagnosis. The following parameters were considered as prerequisites for a diagnosis of inflammatory bowel disease: clinical and endoscopic data; proper sampling and handling of biopsies; and elementary microscopic lesions. We collected 345 cases from 13 centres. The date of onset and treatment were available for 13% and 16% of the cases, respectively. Endoscopy information was accessible for 77% of the cases. Endoscopic mapping was completed in 13% of the cases. In no cases were the biopsies oriented on acetate strips. The diagnosis was conclusive in 47% of the cases. Activity, epithelial disruption and crypt distortion were described in 35% of the reports with a conclusive diagnosis. Our study showed that the diagnostic prerequisites were widely unfulfilled, although approximately half of the diagnoses were conclusive for inflammatory bowel disease. Thus, in our assessment of clinical practice: (1) clinicians seldom provide suitable clinical and/or endoscopic information for a histological diagnosis and (2) histopathological diagnoses of inflammatory bowel disease are often not supported by morphology.
Cancer Cytopathology, 2014
The triage of human papillomavirus (HPV)-positive women is needed to avoid overreferral to colpos... more The triage of human papillomavirus (HPV)-positive women is needed to avoid overreferral to colposcopy. p16INK4a immunostaining is an efficient triage method. p16INK4a/Ki-67 dual staining was introduced mainly to increase reproducibility and specificity compared with stand-alone p16INK4a staining. Within a pilot project, HPV-positive women were referred to colposcopy if cytology was abnormal or unsatisfactory or HPV testing was still positive after 1 year. For 500 consecutive women, a slide obtained during colposcopy was immunostained for p16INK4a/Ki-67 and independently interpreted by 7 readers without previous experience with dual staining. Four of these readers were experts in cervical pathology and 3 were not. Kappa values for multiple raters, sensitivity, and specificity for cervical intraepithelial neoplasia type 2-positive histology were computed. Because women with normal cytology were underrepresented, estimates for all HPV-positive women were obtained as weighted means of cytology-specific estimates. The overall kappa for HPV-positive women was 0.70 (95% confidence interval [95% CI], 0.60-0.77). Kappa values were not found to be significantly different between expert and nonexpert readers with regard to cervical cytology but were significantly increased (P =. 0066) after consensus discussion. The overall specificity estimate for HPV-positive women was 64.0% (95% CI, 57.4%-70.2%): 66.7% (95% CI, 59.8%-73.0%) for experts and 60.5% (95% CI, 59.8%-73.0%) for nonexperts. Among women with abnormal cytology, the sensitivity was 85.5% (95% CI, 77.9%-90.8%): 85.8% (95% CI, 77.9%-91.2%) for experts and 85.1% (95% CI, 76.6%-90.9%) for nonexperts. p16INK4a/Ki-67 immunostaining demonstrated good reproducibility and specificity when triaging HPV-positive women. Dual-staining interpretation can be performed, after short training, even by staff who are not experts in cervical cytology. This allows HPV-based screening with triage to be performed in settings in which such expert staff is not available. Cancer (Cancer Cytopathol) 2014. © 2014 American Cancer Society.
Variation in both nuclear shape and size ("pleom... more Variation in both nuclear shape and size ("pleomorphism"), coupled with changes in chromatin amount and distribution, remains the basic criteria for microscopy in a cytologic diagnosis of cancer. The biological determinants of nuclear shape irregularities are not clarified, so, rather than on the genesis of nuclear irregularities, we here focus our attention on a descriptive analysis of nuclear pleomorphism. We keep in mind that evaluation of nuclear shape as currently practiced in routine preparations is improper because it is indirectly based on the distribution of DNA as revealed by the affinity for basic dyes. Therefore, over the last years we have been using as criteria morphological features of nuclei of thyroid and breast carcinomas as determined by immunofluorescence, in situ hybridization, and 3D reconstruction. We have translated this approach to routine diagnostic pathology on tissue sections by employing immunoperoxidase staining for emerin. Direct detection of nuclear envelope irregularities by tagging nuclear membrane proteins such as lamin B and emerin has resulted in a more objective definition of the shape of the nucleus. In this review we discuss in detail methodological issues as well as diagnostic and prognostic implications provided by decoration/staining of the nuclear envelope in both thyroid and breast cancer, thus demonstrating how much it matters "to be in the right shape" when dealing with pathological diagnosis of cancer.
The primary objectives of this study on carcinomas with equivocal HER2 expression were to assess ... more The primary objectives of this study on carcinomas with equivocal HER2 expression were to assess the impact of distinct recommendations with regard to identifying patients eligible for anti-HER2 agents by fluorescence in situ hybridization (FISH) and to elucidate whether multiplex ligation-dependent probe amplification (MLPA) may be of support in assessing HER2 gene status. A cohort of 957 immunohistochemistry-evaluated HER2-equivocal cases was analyzed by dual-color FISH. The results were assessed according to U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines and American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) 2007 and 2013 guidelines for dual- and single-signal in situ hybridization (ISH) assays. A subgroup of 112 cases was subjected to MLPA. HER2 amplification varied from 15% (ASCO/CAP 2007 HER2/CEP17 ratio) to 29.5% (FDA/EMA HER2 copy number). According to the ASCO/CAP 2013 interpretation of the dual-signal HER2 assay, ISH-positive carcinomas accounted for 19.7%. In contrast with the ASCO/CAP 2007 ratio, this approach labeled as positive all 32 cases (3.34%) with a HER2/CEP17 ratio <2 and an average HER2 copy number ≥6.0 signals per cell. In contrast, only one case showing a HER2 copy number <4 but a ratio ≥2 was diagnosed as positive. MLPA data correlated poorly with FISH results because of the presence of heterogeneous HER2 amplification in 33.9% of all amplified carcinomas; however, MLPA ruled out HER2 amplification in 75% of ISH-evaluated HER2-equivocal carcinomas. The ASCO/CAP 2013 guidelines seem to improve the identification of HER2-positive carcinomas. Polymerase chain reaction-based methods such as MLPA can be of help, provided that heterogeneous amplification has been ruled out by ISH.
Virchows Archiv, 2010
Decoration of the nuclear membrane by emerin staining enhances detection of nuclear irregularitie... more Decoration of the nuclear membrane by emerin staining enhances detection of nuclear irregularities typical of papillary thyroid carcinoma (PTC). Our study aims to verify whether staining with emerin is a helpful diagnostic marker in fine-needle aspiration (FNA) cytology. We first designed a prospective study on smears, Thin Prep, and cell block specimens to prove the feasibility of the procedure; subsequently, we designed a retrospective study of 78 FNA cell blocks from cases that, after surgery, turned out to be either benign (34 cases) or malignant lesions (44, of which 31 PTC). From each sample, we obtained two slides, one stained with hematoxylin and eosin (H&E) and the other with emerin. In cases classified as Thy3, HBME-1 and galectin 3 (Gal3) stains had also been performed. Two blinded observers made the judgment concerning Thy categories (as proposed by the British Thyroid Association), first on H&E, then on emerin, HBME-1, and Gal3 stained slides. On cytological preparation, emerin staining represents an effective tool for the detection of nuclear irregularities, allowing for the identification of cases of PTC. In Thy3 cases, emerin staining's sensitivity and specificity (64% and 96%) proved higher than HBME-1's (60% and 88%) and Gal3's (61% and 68%). In conclusion, the immunohistochemical definition of the nuclear membrane, as determined by emerin stain, is a useful tool in the cytological diagnosis of thyroid lesions and can help to solve inconclusive cases by highlighting nuclear irregularities typical of PTC.
Modern Pathology, 2011
Merkel cell carcinoma of the skin is a malignant neuroendocrine tumour, whose prognostic criteria... more Merkel cell carcinoma of the skin is a malignant neuroendocrine tumour, whose prognostic criteria are a matter of dispute. Specifically, no predictor is presently available in stage I-II tumours. We collected clinical and follow-up data from 70 Merkel cell carcinomas of the skin. The same cases were studied for p63 expression by immunohistochemistry, by reverse-transcription PCR (RT-PCR) and TP63 gene status by FISH and for presence of Merkel cell polyomavirus by PCR. Stage emerged as a significant prognostic parameter (P=0.008). p63 expression, detected in 61% (43/70) of cases by immunohistochemistry, was associated with both decreased overall survival (P<0.0001) and disease-free survival (P<0.0001). Variable expression patterns of the different p63 isoforms were found only in cases immunoreactive for p63. In these latter lesions, at least one of the N-terminal p63 isoforms was detected and TAp63α was the most frequently expressed isoform. TP63 gene amplification was observed by FISH in only one case. Presence of Merkel cell polyomavirus DNA sequences was detected in 86% (60/70) of Merkel cell carcinomas and did not emerge as a significant prognostic parameter. Merkel cell carcinoma cases at low stage (stage I-II) represented over half (40/70 cases, 57%) of cases, and the clinical course was uneventful in 25 of 40 cases while 15 cases died of tumour (10/40 cases) within 34 months or were alive with disease (5/40 cases) within 20 months. Interestingly, a very strict correlation was found between evolution and p63 expression (P<0.0001). The present data indicate that p63 expression is associated with a worse prognosis in patients with Merkel cell carcinoma, and in localised tumours it represents the single independent predictor of clinical evolution.
Head & Neck Surgery, 1987
Chondrosarcoma of the head and neck region is a rarely encountered tumor. Aggressive surgical exc... more Chondrosarcoma of the head and neck region is a rarely encountered tumor. Aggressive surgical excision offers the best chance for cure. In our case, combined diagnostic techniques consisting of fine needle aspiration (FNA), computed tomography (CT), and magnetic resonance imaging (MRI) made an accurate preoperative assessment possible and greatly influenced the treatment provided.
Digestive and Liver Disease, 2011
Diagnostic Cytopathology, 2014
Recent reports indicate that hobnail papillary thyroid carcinoma (HPTC) is a rare, but very aggre... more Recent reports indicate that hobnail papillary thyroid carcinoma (HPTC) is a rare, but very aggressive variant of papillary thyroid carcinoma. The authors describe the cytological features of five HPTC on fine-needle aspiration biopsies (FNAB). Moreover, their immunophenotype and the presence of B-RAF mutation by pyrosequencing were investigated. The patients' (three females and two males) age ranged from 27 to 86 (mean 65) years. Tumor size ranged from 2 to 9 cm (mean 4.2 cm). FNAB were highly cellular with a bloody background and scant colloid. The cells were arranged in papillary-like clusters or in micropapillary groups. The cell population consisted of medium-sized cells with "tear-drop" cytoplasm, apically placed nuclei that produced a surface bulge leading to a hobnail appearance. At higher magnification, nuclei showed variable degrees of atypia, occasional pink intranuclear pseudoinclusions, and grooves. Nuclear stratification and atypical mitotic figures were usually present. Immunocytochemistry revealed positive staining for thyroglobulin, thyroid transcriptor factor-1, Hector Battifora Mesothelial Antigen-1, partial loss of E-cadherin expression, and nuclear expression of p53 protein. B-RAF mutation was present in three out of five cytological cases. Immunohistochemical and molecular results were confirmed on histological sections. Recognizing the unique cytological features of HPTC should help to avoid misdiagnosis of this rare variant. Diagn. Cytopathol. 2014;42:78-84. V C 2013 Wiley Periodicals, Inc.
JNCI Monographs, 2015
Neoadjuvant therapy is increasingly being used in the management of breast cancer patients and, s... more Neoadjuvant therapy is increasingly being used in the management of breast cancer patients and, since comprehensive specimen handling and precise histological reporting is essential to assess the degree of response to therapy, histopathologists are acknowledged to play a key role in this multidisciplinary setting. However, as a matter of fact, only minimal guidelines for specimen handling are on record. This means that in every day routine practice it is not uncommon for oncologists to deal with pathology reports where important parameters are missing (such as formal comments about therapy response). According to the latest American Joint Committee on Cancer (AJCC) staging classification, posttreatment size of residual disease (ypT) should be estimated based on the best combination of imaging, gross and microscopic histological findings. Therefore, pathologists should ideally be provided with clinical and radiological information before proceeding with careful grossing. During the cut-up, large sections or extensive mapping of samples submitted to microscopic evaluation should be carried out to reconstruct the disease extent: this is particularly crucial when the lesion is unapparent both at imaging and at macroscopic observation. Histopathological reports cannot preclude from mandatory information about the presence of residual invasive carcinoma, such as histotyping, staging (ypTNM), reevaluation of prognostic and predictive factors, and categorization of degree of response according to dedicated classification systems (performed by comparing pretreatment biopsies with surgical specimens). In this review we will analyze the critical issues in such an assessment and we will provide a pragmatic approach with the intent to aim at the "perfect" pathology report.