Michela Campora | Trento - Academia.edu (original) (raw)
Papers by Michela Campora
Giornale italiano di dermatologia e venereologia : organo ufficiale, Società italiana di dermatologia e sifilografia, Oct 9, 2020
Autopsy and Case Reports, 2022
Lymphoplasmacyte-rich meningioma (LPRM) is one of the rarest variants of grade I meningiomas. It ... more Lymphoplasmacyte-rich meningioma (LPRM) is one of the rarest variants of grade I meningiomas. It can be clinically associated with prominent peripheral blood abnormalities, anemia, and/or various gammopathy, which usually disappear after surgical removal of the tumor. We document a case of right frontal LPRM in a 72-year-old male who presented general cognitive decadence. The patient suffered from mild anemia. The LPRM is a rare variant of meningioma, with only a few cases globally reported in the literature. It has been categorized as a grade I tumor in the 2021 World Health Organization (WHO) classification central nervous system. Due to the rarity, this meningioma variant origin and biological behavior are still not clear. Immunohistochemistry profile showed prominent PD-L1 expression, leading to additional interrogation on LPRM immunomorphological characteristics, the significance of the inflammatory tumoral microenvironment and its correlation with the immune-checkpoints.
Frontiers in Surgery, Mar 23, 2023
Adenoid cystic carcinoma (AdCC) is a rare tumor that typically develops in the salivary glands an... more Adenoid cystic carcinoma (AdCC) is a rare tumor that typically develops in the salivary glands and less frequently in other sites of the head and neck region. Only a few cases of resected metachronous liver metastases have been reported. Minimally invasive surgery is currently the gold standard of care for liver resections; furthermore, the use of Indocyanine Green (ICG) is continuously increasing in surgical practice, especially in cases of primary liver tumors and colorectal liver metastases, due to its capacity to enhance liver nodules. We report the case of a 54-year-old male with a single liver metastasis of AdCC, located in SIII, who presented in our center 9 months after resection of a primary tumor of the laryngotracheal junction and adjuvant proton therapy. A 25-mg injection of ICG (0.3 mg/kg) was administered 48 h before surgery in order to highlight the tumor and perform an ICG-guided resection. The lesion was clearly visible during surgery, and, given its position and the proximity to the main lobar vessels of the left lobe, we opted for a left lateral sectionectomy. The outcome was unremarkable, with no major postoperative complications. The administration of ICG 48 h before surgery seems to be a valid tool even in cases of AdCC liver metastases, providing surgeons with better visualization of the lesion and improving the precision of the resection.
Italian journal of dermatology and venereology, May 1, 2021
Pathologica, Apr 1, 2023
PD-L1 is an established predictive immunohistochemical biomarker of response to immune checkpoint... more PD-L1 is an established predictive immunohistochemical biomarker of response to immune checkpoint inhibitors. At present, PD-L1 is routinely assessed on biopsy samples of advanced gastroesophageal cancer patients before initiating first-line treatment. However, PD-L1 is still a suboptimal biomarker, due to changing cutoff values and scoring systems, interobserver and interlaboratory variability. This practical illustrated review discusses the range of staining patterns of PD-L1 and the potential pitfalls and challenges that can be encountered when evaluating PD-L1, focusing on gastric and gastroesophageal adenocarcinoma (G/GEA) and esophageal squamous cell carcinoma (ESCC).
Frontiers in Medicine, Apr 14, 2021
Introduction: Seeds may be found in gastrointestinal tissue samples, and their multifaceted appea... more Introduction: Seeds may be found in gastrointestinal tissue samples, and their multifaceted appearance may be challenging. The aim is to report a rough incidence of pathology samples which show seeds, specify the most frequent sample types and show an iconography of the most commonly identified seeds. Materials and Methods: Between 2017 and 2020, all gastrointestinal pathology cases in which seeds/seed parts were found, were collected and seed type described by referencing a seed image library. Results: Fifty cases with complete seeds/seed parts were collected: 16 colonic resections for colorectal cancer and diverticulosis, 13 appendiceal resections for appendicitis, 1 gastric resection. Fifteen cases were found in polypectomy specimens and 5 cases in colorectal endoscopic biopsies. Most frequent seed types were tomato, kiwi, blueberry, and blackberry seeds. Conclusion: Seeds may be found in up to 4% of specimens; their recognition may be useful to exclude parasitic infections as well as in forensic sciences.
Histochemistry and Cell Biology, Jan 2, 2019
Formalin is toxic and has recently been classified as carcinogenic leading to a proposed European... more Formalin is toxic and has recently been classified as carcinogenic leading to a proposed European formalin ban. But, the pathology use of formalin has however been completely overlooked, and this is proving to be a relevant issue, as no alternative, reliable, tissue fixative is available. Various systems have been proposed to reduce formalin use and exposure; longterm storage and disposal of formalin is also a problem. With this in mind, under vacuum sealing (UVS) systems have been proposed for transportation/storage, however, for how long tissue retains its characteristics (morphological and molecular) is unknown. This study aims to compare histology specimens stored by formalin immersion (FI) and specimens stored after fixation with UVS technique with no additional formalin, at different time periods. Twenty tissue samples (10FI; 10UVS) were stored for different time periods (15 days, 1-2-3-6-12 months) for a total of 120 samples, compared with regard to their morphology, histochemistry, immunoreactivity (24 specific antibodies) and DNA status. All samples showed well-preserved morphology and overlapping staining quality. A significant reduction in immunoreactivity was however identified in the various time periods, particularly for heat pre-treated nuclear antigens, and this commenced earlier (1 month) for FI. UVS storage showed higher DNA content than FI but slightly poorer DNA integrity. These results add important knowledge to the use of UVS in daily practice, as long-term storage of prefixed tissue in UVS is not detrimental to the quality of tissue while having the boon of using very little formalin with less operator exposure and lower disposal costs.
Pathologica, Oct 1, 2022
Immune-checkpoint inhibitors targeting the PD-1/PD-L1 axis have brought significant clinical bene... more Immune-checkpoint inhibitors targeting the PD-1/PD-L1 axis have brought significant clinical benefit in many solid cancer types, including gastrointestinal malignancies. However, it has been estimated that only 20-40% of patients respond to treatment. The pattern of expression and potential predictive value of PD-L1 as an immunohistochemical biomarker has been extensively studied in gastrointestinal neoplasms. Until now, its predictive value has been demonstrated, and is currently in use only in upper gastrointestinal malignancies (gastroesophageal adenocarcinoma and esophageal squamous cell carcinoma). In this Review, we describe the technical aspects and challenges related to PD-L1 immunohistochemical assays, the current role of PD-L1 as a biomarker in clinical practice and we outline the main studies and clinical trials analyzing the prognostic and predictive value of PD-L1 in gastrointestinal cancers.
International Journal of Surgical Pathology, Mar 14, 2019
Thyroid ectopia is a rare finding below the diaphragm. It is characterized by normal thyroid pare... more Thyroid ectopia is a rare finding below the diaphragm. It is characterized by normal thyroid parenchyma in unusual locations with preserved thyroid marker immunoreactivity. In this article, we present the first known case of thyroid tissue in the periappendiceal fat and discuss possible ethiopathogenic theories.
Journal of Clinical Pathology, Apr 13, 2023
AimsIn the DESTINY-Gastric01 trial, a novel HER2-targeted antibody-drug conjugate trastuzumab der... more AimsIn the DESTINY-Gastric01 trial, a novel HER2-targeted antibody-drug conjugate trastuzumab deruxtecan proved to be effective in HER2-low gastro-oesophageal adenocarcinomas. The aim of our study is to investigate the clinicopathological and molecular features of HER2-low gastric/gastro-oesophageal junction cancers in the real-world setting of a large multi-Institutional series.MethodsWe retrospectively evaluated 1210 formalin-fixed paraffin-embedded samples of gastro-oesophageal adenocarcinomas which were analysed by immunohistochemistry for HER2 protein expression in 8 Italian surgical pathology units from January 2018 to June 2022. We assessed the prevalence of HER2-low (ie, HER2 1+ and HER2 2+ without amplification) and its correlation with clinical and histopathological features, other biomarkers’ status, including mismatch repair/microsatellite instability status, Epstein-Barr encoding region (EBER) and PD-L1 Combined Positive Score.ResultsHER2 status could be assessed in 1189/1210 cases, including 710 HER2 0 cases, 217 HER2 1+, 120 not amplified HER2 2+, 41 amplified HER2 2+ and 101 HER2 3+. The estimated prevalence of HER2-low was 28.3% (95% CI 25.8% to 31.0%) overall, and was higher in biopsy specimens (34.9%, 95% CI 31.2% to 38.8%) compared with surgical resection specimens (21.0%, 95% CI 17.7% to 24.6%) (p<0.0001). Moreover, HER2-low prevalence ranged from 19.1% to 40.6% among centres (p=0.0005).ConclusionsThis work shows how the expansion of the HER2 spectrum might raise problems in reproducibility, especially in biopsy specimens, decreasing interlaboratory and interobserver concordance. If controlled trials confirm the promising activity of novel anti-HER2 agents in HER2-low gastro-oesophageal cancers, a shift in the interpretation of HER2 status may need to be pursued.
Virchows Archiv, Oct 1, 2021
Organic (such as parasites or vegetable remnants) and inorganic substances may be encountered dur... more Organic (such as parasites or vegetable remnants) and inorganic substances may be encountered during routine pathology diagnostic work up of endoscopic gastrointestinal biopsy samples and major resections, causing possible diagnostic conundrums for the young and not so young pathologists. The main aim of this review is the description of the most frequent oddities one can encounter as foreign bodies, in gastrointestinal pathology, on the basis of the current literature and personal experience. The types of encountered substances are divided into four principal categories: parasites (helminths such as Enterobius vermicularis, Strongyloides, Schistosoma, and Anisakis, and protozoa such as Entamoeba, Giardia and some intestinal coccidia); drugs and pharmaceutical fillers (found as deposits and as bystanders, innocent or not); seeds (possibly confused with worms) and plant remnants; pollutants (secondary to post-resection or post-biopsy contamination of the sample). An ample library of images is provided in order to consent easy referencing for diagnostic routine.
Pathologica, Feb 1, 2021
Neuroendocrine neoplasms of the appendix, colon and rectum are classified according to the most r... more Neuroendocrine neoplasms of the appendix, colon and rectum are classified according to the most recent WHO classification as neuroendocrine tumors (NET), neuroendocrine carcinomas (NEC) and mixed neuroendocrine-non neuroendocrine neoplasms (MiNENs). NECs and MiNENs are aggressive neoplasms requiring multimodal treatment strategies. By contrast, NETs are, in most cases, indolent lesions occurring as incidental findings in the appendix or as polyps in the rectum. While most appendiceal and rectal NETs are considered relatively non-aggressive neoplasms, a few cases, may show a more aggressive clinical course. Unfortunately, clinical/pathological characteristics to select patients at high risk of recurrence/metastases are poorly consolidated. Diagnosis is generally easy and supported by the combination of morphology and immunohistochemistry. Differential diagnostic problems are for NECs/MiNENs with poorly differentiated adenocarcinomas, when immunohistochemical neuroendocrine markers are not obviously positive, whereas for NETs they are represented by the rare appendiceal tubular and clear cell variants (which may be confused with non-neuroendocrine cancers) and rectal L-cell tumors which may be chromogranin negative and prostatic marker positive.
Pathologica, Sep 1, 2020
The first part of this overview on non-neoplastic esophagus is focused on gastro-esophageal reflu... more The first part of this overview on non-neoplastic esophagus is focused on gastro-esophageal reflux disease (GERD) and Barrett's esophagus. In the last 20 years much has changed in histological approach to biopsies of patients with gastro-esophageal reflux disease. In particular, elementary histologic lesions have been well defined and modality of evaluation and grade are detailed, their sensitivity and specificity has been evaluated and their use has been validated by several authors. Also if there is not a clinical indication to perform biopsies in patient with GERD, the diagnosis of microscopic esophagitis, when biopsies are provided, can be performed by following simple rules for evaluation which allow pathologists to make the diagnosis with confidence. On the other hand, biopsies are required for the diagnosis of Barrett's esophagus. This diagnosis is the synthesis of endoscopic picture (which has to be provided with the proper description on extent and with adequate biopsies number) and histologic pattern. The current guidelines and expert opinions for the correct management of these diagnosis are detailed.
Histopathology, Mar 22, 2021
AimsPhyllodes tumours (PTs) represent an unusual but complex group of breast lesions with a tende... more AimsPhyllodes tumours (PTs) represent an unusual but complex group of breast lesions with a tendency to recur locally and, less commonly, metastasise. On core biopsies, their appearances can be difficult to discriminate from those of other fibroepithelial lesions, which may compromise their surgical management. The aims of this study were to assess the preoperative diagnosis of PTs and to evaluate the impacts of surgical management and morphological features on their behaviour.Methods and resultsWe combined datasets from three centres over two decades, including core biopsies, excision specimens, and follow‐up. Core biopsy results were compared with final excision specimens. The relationships of surgical procedure and morphological features with local recurrence (LR) and metastasis were assessed. Two hundred and forty‐one PTs were studied. Core biopsy resulted in a diagnosis of possible or definite PT in 76% of cases. Malignant tumours were more likely to be larger, occurred at an older age, and were surgically more challenging, with difficulties being encountered in achieving negative margins. There were 12 cases (5%) that showed LR alone, and another six cases (2.5%) that had distant metastases. Morphological features associated with adverse outcome were grade of PT, increased mitotic counts, necrosis, infiltrative margins, stromal atypia, and heterologous components. Both LR and metastatic behaviour correlated with larger size and distance to margins.ConclusionsOur results suggest that excision margins have a significant impact on LR of PT, whereas metastatic behaviour is influenced by tumour biology. We add to the evidence base on histological features of tumours that contribute to long‐term outcomes of PT patients.
To the Editors: Six years after the publication of the last case of inflammatory testicular pseud... more To the Editors: Six years after the publication of the last case of inflammatory testicular pseudotumor,1 we have a further case to add to the overview of the pseudoneoplastic entities arising in the testis and paratesticular structure,2 particularly interesting for its clinical management. A 70-year-old man presented with an asymptomatic, palpable nodule at the right testis. Ultrasonography (US) showed an 8-mm, solid, vascularized lesion at the testicular surface (Figure 1A). Testicular markers were normal.
Histochemistry and Cell Biology, Jul 28, 2022
Identifying innovative molecules involved in the tumor immune escape process could help refine th... more Identifying innovative molecules involved in the tumor immune escape process could help refine the survival stratification of colorectal cancer (CRC) patients. HLA-G, a non-classical HLA molecule, physiologically involved in tolerogenic mechanisms, has recently emerged as a relevant prognostic marker in other tumor types, but ambiguous data are reported in the CRC setting. This study aims to evaluate the HLA-G expression and prognostic potential in a series of stage II/III CRCs. HLA-G expression was evaluated in 100 pT3 CRC cases by means of immunohistochemistry using the 4H84 and MEM-G/2 monoclonal antibodies. We observed heterogeneous expression of HLA-G showing different ranges: 4H84 expression ranged from > 1 to 40%-median 7%; MEM-G/2 expression ranged from 20 to 90%-median 50%. HLA-G positivity (any intensity > 1%) varied according to the antibody employed, identifying: 8 4H84 positive, 34 MEM-G/2 positive, 6 double-positive and 52 negative cases. Correlation with clinico-pathologic data showed a significant association with a poor tumor differentiation in stage III right-sided CRC subgroup (p = 0.043), while no other pathologic variable was significantly associated. Survival analysis revealed a reduced disease-free survival rate (HR 4.304613; p = 0.031) in the subgroup of CRC-related death cases, while no correlations were observed considering the whole series and the overall survival. In conclusion, HLA-G is a promising CRC prognostic marker however much work is still required regarding technical aspects and evaluation of expression.
Pathologica, Feb 1, 2022
Children are not simply miniature adults. The evaluation of their gastrointestinal disorders is t... more Children are not simply miniature adults. The evaluation of their gastrointestinal disorders is therefore different from that in full-grown adults and requires a particular clinical/pathologic approach. Different studies have tried to assess the normal eosinophil distribution in the gastrointestinal tract in adults while very few studies have investigated the paediatric population, consequently complicating the pathologist's ability in identifying an abnormal number of eosinophils in this setting of patients. When evaluating gastrointestinal tract biopsies with eosinophilia, eosinophilic count must be considered along with other histological features like eosinophil distribution in the gastrointestinal wall, their degranulation, cryptitis and crypt abscesses, other accompanying inflammatory cells, apoptotic bodies, foreign material or microorganisms; these findings, although rarely specific, may be a useful aid for diagnosis. Reports should not include a diagnosis of primary eosinophilic gastrointestinal disorders (EoGID) if clinical data and test results do not rule out other forms of gastrointestinal eosinophilia. A more descriptive definition like "with eosinophilic pattern" should be favoured over a specific diagnosis of "eosinophilic disorder" in order to avoid potential confusion between different entities.
Histochemistry and Cell Biology, Apr 10, 2021
Pathology archives are a treasure trove of paraffin embedded tissue spanning many years and cover... more Pathology archives are a treasure trove of paraffin embedded tissue spanning many years and covering a wide variety of tissues and diseases. The possibility of using old archival formalin fixed paraffin embedded (FFPE) tissues for diagnostic updates and research projects is a widespread need and it requires archives of stable, well-preserved samples. Immunohistochemistry performed on old archival paraffin blocks may give unreliable results, in particular for some antigens, such as Ki67. In consideration of this phenomenon, our aim is to comprehensively test and identify methods which may be used to obtain Ki67 immunohistochemical reactions of good quality from old archival FFPE blocks. Various methods were tested in order to evaluate their possible efficacy in increasing Ki67 immunointensity in a collection of 40-year-old, archival blocks including re-embedding, with deeper sectioning of tissue from the block and increasing heat-based pretreatment times (20 cases) and reprocessing (20 cases). All reactions were performed using an automated immunostainer and Ki67 stained immunosections compared using a visual colour-based scale (the first immunostained section was considered as baseline). The combination of deep sectioning (1000 µM) and prolonged heat-based pretreatment (64 min) markedly increased immunoreactivity for Ki67. Re-embedding and reprocessing did not have a significant effect. Large tissue samples showed heterogeneity of Ki67 immunoexpression between the periphery of the sample and the central area. In conclusion, the study defines a useful protocol to increase antigen retrieval applicable to dated archival tissues.
Virchows Archiv, Nov 23, 2022
Mitotic count (MC) is an important prognostic indicator in gastrointestinal stromal tumours (GIST... more Mitotic count (MC) is an important prognostic indicator in gastrointestinal stromal tumours (GISTs). Though MC evaluation was initially proposed in 50 HPFs, recent international guidelines recommend that MC be performed on 5 mm 2 because HPFs may have different areas depending on the ocular field number (FN) of the utilized light microscope. Performing MC on different areas leads to a non-standardized evaluation and erroneous risk stratification. The aim of the study was to audit real-life MC practices with special emphasis on possible risk stratification errors. A survey was administered to Italian pathologists to evaluate the following: method used for MC (5 mm 2 versus 50 HPF); FN of the light microscope; prognostic scheme for risk stratification. Based on the results of the survey, 100 GISTs (25/risk class using Miettinen prognostic scheme) were retrieved and MC performed using 5 mm 2 versus the corresponding mm 2 area sizes of 50 HPFs with variable FNs (18, 20, 22). The survey demonstrated that the majority of pathologists (64.5%) use 50 HPFs with various FNs leading to excessive area size. The most frequently used prognostic scheme is that by Miettinen. Using this prognostic scheme and counting mitoses in 5 mm 2 versus 50 HPFs with FNs 18, 20 and 22, a change in risk class was identified ranging from 10 to 41%, depending on FN. In conclusion, this study demonstrates that MC is still frequently performed on 50 HPF, with area sizes exceeding the specified 5 mm 2 by far.
Giornale italiano di dermatologia e venereologia : organo ufficiale, Società italiana di dermatologia e sifilografia, Oct 9, 2020
Autopsy and Case Reports, 2022
Lymphoplasmacyte-rich meningioma (LPRM) is one of the rarest variants of grade I meningiomas. It ... more Lymphoplasmacyte-rich meningioma (LPRM) is one of the rarest variants of grade I meningiomas. It can be clinically associated with prominent peripheral blood abnormalities, anemia, and/or various gammopathy, which usually disappear after surgical removal of the tumor. We document a case of right frontal LPRM in a 72-year-old male who presented general cognitive decadence. The patient suffered from mild anemia. The LPRM is a rare variant of meningioma, with only a few cases globally reported in the literature. It has been categorized as a grade I tumor in the 2021 World Health Organization (WHO) classification central nervous system. Due to the rarity, this meningioma variant origin and biological behavior are still not clear. Immunohistochemistry profile showed prominent PD-L1 expression, leading to additional interrogation on LPRM immunomorphological characteristics, the significance of the inflammatory tumoral microenvironment and its correlation with the immune-checkpoints.
Frontiers in Surgery, Mar 23, 2023
Adenoid cystic carcinoma (AdCC) is a rare tumor that typically develops in the salivary glands an... more Adenoid cystic carcinoma (AdCC) is a rare tumor that typically develops in the salivary glands and less frequently in other sites of the head and neck region. Only a few cases of resected metachronous liver metastases have been reported. Minimally invasive surgery is currently the gold standard of care for liver resections; furthermore, the use of Indocyanine Green (ICG) is continuously increasing in surgical practice, especially in cases of primary liver tumors and colorectal liver metastases, due to its capacity to enhance liver nodules. We report the case of a 54-year-old male with a single liver metastasis of AdCC, located in SIII, who presented in our center 9 months after resection of a primary tumor of the laryngotracheal junction and adjuvant proton therapy. A 25-mg injection of ICG (0.3 mg/kg) was administered 48 h before surgery in order to highlight the tumor and perform an ICG-guided resection. The lesion was clearly visible during surgery, and, given its position and the proximity to the main lobar vessels of the left lobe, we opted for a left lateral sectionectomy. The outcome was unremarkable, with no major postoperative complications. The administration of ICG 48 h before surgery seems to be a valid tool even in cases of AdCC liver metastases, providing surgeons with better visualization of the lesion and improving the precision of the resection.
Italian journal of dermatology and venereology, May 1, 2021
Pathologica, Apr 1, 2023
PD-L1 is an established predictive immunohistochemical biomarker of response to immune checkpoint... more PD-L1 is an established predictive immunohistochemical biomarker of response to immune checkpoint inhibitors. At present, PD-L1 is routinely assessed on biopsy samples of advanced gastroesophageal cancer patients before initiating first-line treatment. However, PD-L1 is still a suboptimal biomarker, due to changing cutoff values and scoring systems, interobserver and interlaboratory variability. This practical illustrated review discusses the range of staining patterns of PD-L1 and the potential pitfalls and challenges that can be encountered when evaluating PD-L1, focusing on gastric and gastroesophageal adenocarcinoma (G/GEA) and esophageal squamous cell carcinoma (ESCC).
Frontiers in Medicine, Apr 14, 2021
Introduction: Seeds may be found in gastrointestinal tissue samples, and their multifaceted appea... more Introduction: Seeds may be found in gastrointestinal tissue samples, and their multifaceted appearance may be challenging. The aim is to report a rough incidence of pathology samples which show seeds, specify the most frequent sample types and show an iconography of the most commonly identified seeds. Materials and Methods: Between 2017 and 2020, all gastrointestinal pathology cases in which seeds/seed parts were found, were collected and seed type described by referencing a seed image library. Results: Fifty cases with complete seeds/seed parts were collected: 16 colonic resections for colorectal cancer and diverticulosis, 13 appendiceal resections for appendicitis, 1 gastric resection. Fifteen cases were found in polypectomy specimens and 5 cases in colorectal endoscopic biopsies. Most frequent seed types were tomato, kiwi, blueberry, and blackberry seeds. Conclusion: Seeds may be found in up to 4% of specimens; their recognition may be useful to exclude parasitic infections as well as in forensic sciences.
Histochemistry and Cell Biology, Jan 2, 2019
Formalin is toxic and has recently been classified as carcinogenic leading to a proposed European... more Formalin is toxic and has recently been classified as carcinogenic leading to a proposed European formalin ban. But, the pathology use of formalin has however been completely overlooked, and this is proving to be a relevant issue, as no alternative, reliable, tissue fixative is available. Various systems have been proposed to reduce formalin use and exposure; longterm storage and disposal of formalin is also a problem. With this in mind, under vacuum sealing (UVS) systems have been proposed for transportation/storage, however, for how long tissue retains its characteristics (morphological and molecular) is unknown. This study aims to compare histology specimens stored by formalin immersion (FI) and specimens stored after fixation with UVS technique with no additional formalin, at different time periods. Twenty tissue samples (10FI; 10UVS) were stored for different time periods (15 days, 1-2-3-6-12 months) for a total of 120 samples, compared with regard to their morphology, histochemistry, immunoreactivity (24 specific antibodies) and DNA status. All samples showed well-preserved morphology and overlapping staining quality. A significant reduction in immunoreactivity was however identified in the various time periods, particularly for heat pre-treated nuclear antigens, and this commenced earlier (1 month) for FI. UVS storage showed higher DNA content than FI but slightly poorer DNA integrity. These results add important knowledge to the use of UVS in daily practice, as long-term storage of prefixed tissue in UVS is not detrimental to the quality of tissue while having the boon of using very little formalin with less operator exposure and lower disposal costs.
Pathologica, Oct 1, 2022
Immune-checkpoint inhibitors targeting the PD-1/PD-L1 axis have brought significant clinical bene... more Immune-checkpoint inhibitors targeting the PD-1/PD-L1 axis have brought significant clinical benefit in many solid cancer types, including gastrointestinal malignancies. However, it has been estimated that only 20-40% of patients respond to treatment. The pattern of expression and potential predictive value of PD-L1 as an immunohistochemical biomarker has been extensively studied in gastrointestinal neoplasms. Until now, its predictive value has been demonstrated, and is currently in use only in upper gastrointestinal malignancies (gastroesophageal adenocarcinoma and esophageal squamous cell carcinoma). In this Review, we describe the technical aspects and challenges related to PD-L1 immunohistochemical assays, the current role of PD-L1 as a biomarker in clinical practice and we outline the main studies and clinical trials analyzing the prognostic and predictive value of PD-L1 in gastrointestinal cancers.
International Journal of Surgical Pathology, Mar 14, 2019
Thyroid ectopia is a rare finding below the diaphragm. It is characterized by normal thyroid pare... more Thyroid ectopia is a rare finding below the diaphragm. It is characterized by normal thyroid parenchyma in unusual locations with preserved thyroid marker immunoreactivity. In this article, we present the first known case of thyroid tissue in the periappendiceal fat and discuss possible ethiopathogenic theories.
Journal of Clinical Pathology, Apr 13, 2023
AimsIn the DESTINY-Gastric01 trial, a novel HER2-targeted antibody-drug conjugate trastuzumab der... more AimsIn the DESTINY-Gastric01 trial, a novel HER2-targeted antibody-drug conjugate trastuzumab deruxtecan proved to be effective in HER2-low gastro-oesophageal adenocarcinomas. The aim of our study is to investigate the clinicopathological and molecular features of HER2-low gastric/gastro-oesophageal junction cancers in the real-world setting of a large multi-Institutional series.MethodsWe retrospectively evaluated 1210 formalin-fixed paraffin-embedded samples of gastro-oesophageal adenocarcinomas which were analysed by immunohistochemistry for HER2 protein expression in 8 Italian surgical pathology units from January 2018 to June 2022. We assessed the prevalence of HER2-low (ie, HER2 1+ and HER2 2+ without amplification) and its correlation with clinical and histopathological features, other biomarkers’ status, including mismatch repair/microsatellite instability status, Epstein-Barr encoding region (EBER) and PD-L1 Combined Positive Score.ResultsHER2 status could be assessed in 1189/1210 cases, including 710 HER2 0 cases, 217 HER2 1+, 120 not amplified HER2 2+, 41 amplified HER2 2+ and 101 HER2 3+. The estimated prevalence of HER2-low was 28.3% (95% CI 25.8% to 31.0%) overall, and was higher in biopsy specimens (34.9%, 95% CI 31.2% to 38.8%) compared with surgical resection specimens (21.0%, 95% CI 17.7% to 24.6%) (p<0.0001). Moreover, HER2-low prevalence ranged from 19.1% to 40.6% among centres (p=0.0005).ConclusionsThis work shows how the expansion of the HER2 spectrum might raise problems in reproducibility, especially in biopsy specimens, decreasing interlaboratory and interobserver concordance. If controlled trials confirm the promising activity of novel anti-HER2 agents in HER2-low gastro-oesophageal cancers, a shift in the interpretation of HER2 status may need to be pursued.
Virchows Archiv, Oct 1, 2021
Organic (such as parasites or vegetable remnants) and inorganic substances may be encountered dur... more Organic (such as parasites or vegetable remnants) and inorganic substances may be encountered during routine pathology diagnostic work up of endoscopic gastrointestinal biopsy samples and major resections, causing possible diagnostic conundrums for the young and not so young pathologists. The main aim of this review is the description of the most frequent oddities one can encounter as foreign bodies, in gastrointestinal pathology, on the basis of the current literature and personal experience. The types of encountered substances are divided into four principal categories: parasites (helminths such as Enterobius vermicularis, Strongyloides, Schistosoma, and Anisakis, and protozoa such as Entamoeba, Giardia and some intestinal coccidia); drugs and pharmaceutical fillers (found as deposits and as bystanders, innocent or not); seeds (possibly confused with worms) and plant remnants; pollutants (secondary to post-resection or post-biopsy contamination of the sample). An ample library of images is provided in order to consent easy referencing for diagnostic routine.
Pathologica, Feb 1, 2021
Neuroendocrine neoplasms of the appendix, colon and rectum are classified according to the most r... more Neuroendocrine neoplasms of the appendix, colon and rectum are classified according to the most recent WHO classification as neuroendocrine tumors (NET), neuroendocrine carcinomas (NEC) and mixed neuroendocrine-non neuroendocrine neoplasms (MiNENs). NECs and MiNENs are aggressive neoplasms requiring multimodal treatment strategies. By contrast, NETs are, in most cases, indolent lesions occurring as incidental findings in the appendix or as polyps in the rectum. While most appendiceal and rectal NETs are considered relatively non-aggressive neoplasms, a few cases, may show a more aggressive clinical course. Unfortunately, clinical/pathological characteristics to select patients at high risk of recurrence/metastases are poorly consolidated. Diagnosis is generally easy and supported by the combination of morphology and immunohistochemistry. Differential diagnostic problems are for NECs/MiNENs with poorly differentiated adenocarcinomas, when immunohistochemical neuroendocrine markers are not obviously positive, whereas for NETs they are represented by the rare appendiceal tubular and clear cell variants (which may be confused with non-neuroendocrine cancers) and rectal L-cell tumors which may be chromogranin negative and prostatic marker positive.
Pathologica, Sep 1, 2020
The first part of this overview on non-neoplastic esophagus is focused on gastro-esophageal reflu... more The first part of this overview on non-neoplastic esophagus is focused on gastro-esophageal reflux disease (GERD) and Barrett's esophagus. In the last 20 years much has changed in histological approach to biopsies of patients with gastro-esophageal reflux disease. In particular, elementary histologic lesions have been well defined and modality of evaluation and grade are detailed, their sensitivity and specificity has been evaluated and their use has been validated by several authors. Also if there is not a clinical indication to perform biopsies in patient with GERD, the diagnosis of microscopic esophagitis, when biopsies are provided, can be performed by following simple rules for evaluation which allow pathologists to make the diagnosis with confidence. On the other hand, biopsies are required for the diagnosis of Barrett's esophagus. This diagnosis is the synthesis of endoscopic picture (which has to be provided with the proper description on extent and with adequate biopsies number) and histologic pattern. The current guidelines and expert opinions for the correct management of these diagnosis are detailed.
Histopathology, Mar 22, 2021
AimsPhyllodes tumours (PTs) represent an unusual but complex group of breast lesions with a tende... more AimsPhyllodes tumours (PTs) represent an unusual but complex group of breast lesions with a tendency to recur locally and, less commonly, metastasise. On core biopsies, their appearances can be difficult to discriminate from those of other fibroepithelial lesions, which may compromise their surgical management. The aims of this study were to assess the preoperative diagnosis of PTs and to evaluate the impacts of surgical management and morphological features on their behaviour.Methods and resultsWe combined datasets from three centres over two decades, including core biopsies, excision specimens, and follow‐up. Core biopsy results were compared with final excision specimens. The relationships of surgical procedure and morphological features with local recurrence (LR) and metastasis were assessed. Two hundred and forty‐one PTs were studied. Core biopsy resulted in a diagnosis of possible or definite PT in 76% of cases. Malignant tumours were more likely to be larger, occurred at an older age, and were surgically more challenging, with difficulties being encountered in achieving negative margins. There were 12 cases (5%) that showed LR alone, and another six cases (2.5%) that had distant metastases. Morphological features associated with adverse outcome were grade of PT, increased mitotic counts, necrosis, infiltrative margins, stromal atypia, and heterologous components. Both LR and metastatic behaviour correlated with larger size and distance to margins.ConclusionsOur results suggest that excision margins have a significant impact on LR of PT, whereas metastatic behaviour is influenced by tumour biology. We add to the evidence base on histological features of tumours that contribute to long‐term outcomes of PT patients.
To the Editors: Six years after the publication of the last case of inflammatory testicular pseud... more To the Editors: Six years after the publication of the last case of inflammatory testicular pseudotumor,1 we have a further case to add to the overview of the pseudoneoplastic entities arising in the testis and paratesticular structure,2 particularly interesting for its clinical management. A 70-year-old man presented with an asymptomatic, palpable nodule at the right testis. Ultrasonography (US) showed an 8-mm, solid, vascularized lesion at the testicular surface (Figure 1A). Testicular markers were normal.
Histochemistry and Cell Biology, Jul 28, 2022
Identifying innovative molecules involved in the tumor immune escape process could help refine th... more Identifying innovative molecules involved in the tumor immune escape process could help refine the survival stratification of colorectal cancer (CRC) patients. HLA-G, a non-classical HLA molecule, physiologically involved in tolerogenic mechanisms, has recently emerged as a relevant prognostic marker in other tumor types, but ambiguous data are reported in the CRC setting. This study aims to evaluate the HLA-G expression and prognostic potential in a series of stage II/III CRCs. HLA-G expression was evaluated in 100 pT3 CRC cases by means of immunohistochemistry using the 4H84 and MEM-G/2 monoclonal antibodies. We observed heterogeneous expression of HLA-G showing different ranges: 4H84 expression ranged from > 1 to 40%-median 7%; MEM-G/2 expression ranged from 20 to 90%-median 50%. HLA-G positivity (any intensity > 1%) varied according to the antibody employed, identifying: 8 4H84 positive, 34 MEM-G/2 positive, 6 double-positive and 52 negative cases. Correlation with clinico-pathologic data showed a significant association with a poor tumor differentiation in stage III right-sided CRC subgroup (p = 0.043), while no other pathologic variable was significantly associated. Survival analysis revealed a reduced disease-free survival rate (HR 4.304613; p = 0.031) in the subgroup of CRC-related death cases, while no correlations were observed considering the whole series and the overall survival. In conclusion, HLA-G is a promising CRC prognostic marker however much work is still required regarding technical aspects and evaluation of expression.
Pathologica, Feb 1, 2022
Children are not simply miniature adults. The evaluation of their gastrointestinal disorders is t... more Children are not simply miniature adults. The evaluation of their gastrointestinal disorders is therefore different from that in full-grown adults and requires a particular clinical/pathologic approach. Different studies have tried to assess the normal eosinophil distribution in the gastrointestinal tract in adults while very few studies have investigated the paediatric population, consequently complicating the pathologist's ability in identifying an abnormal number of eosinophils in this setting of patients. When evaluating gastrointestinal tract biopsies with eosinophilia, eosinophilic count must be considered along with other histological features like eosinophil distribution in the gastrointestinal wall, their degranulation, cryptitis and crypt abscesses, other accompanying inflammatory cells, apoptotic bodies, foreign material or microorganisms; these findings, although rarely specific, may be a useful aid for diagnosis. Reports should not include a diagnosis of primary eosinophilic gastrointestinal disorders (EoGID) if clinical data and test results do not rule out other forms of gastrointestinal eosinophilia. A more descriptive definition like "with eosinophilic pattern" should be favoured over a specific diagnosis of "eosinophilic disorder" in order to avoid potential confusion between different entities.
Histochemistry and Cell Biology, Apr 10, 2021
Pathology archives are a treasure trove of paraffin embedded tissue spanning many years and cover... more Pathology archives are a treasure trove of paraffin embedded tissue spanning many years and covering a wide variety of tissues and diseases. The possibility of using old archival formalin fixed paraffin embedded (FFPE) tissues for diagnostic updates and research projects is a widespread need and it requires archives of stable, well-preserved samples. Immunohistochemistry performed on old archival paraffin blocks may give unreliable results, in particular for some antigens, such as Ki67. In consideration of this phenomenon, our aim is to comprehensively test and identify methods which may be used to obtain Ki67 immunohistochemical reactions of good quality from old archival FFPE blocks. Various methods were tested in order to evaluate their possible efficacy in increasing Ki67 immunointensity in a collection of 40-year-old, archival blocks including re-embedding, with deeper sectioning of tissue from the block and increasing heat-based pretreatment times (20 cases) and reprocessing (20 cases). All reactions were performed using an automated immunostainer and Ki67 stained immunosections compared using a visual colour-based scale (the first immunostained section was considered as baseline). The combination of deep sectioning (1000 µM) and prolonged heat-based pretreatment (64 min) markedly increased immunoreactivity for Ki67. Re-embedding and reprocessing did not have a significant effect. Large tissue samples showed heterogeneity of Ki67 immunoexpression between the periphery of the sample and the central area. In conclusion, the study defines a useful protocol to increase antigen retrieval applicable to dated archival tissues.
Virchows Archiv, Nov 23, 2022
Mitotic count (MC) is an important prognostic indicator in gastrointestinal stromal tumours (GIST... more Mitotic count (MC) is an important prognostic indicator in gastrointestinal stromal tumours (GISTs). Though MC evaluation was initially proposed in 50 HPFs, recent international guidelines recommend that MC be performed on 5 mm 2 because HPFs may have different areas depending on the ocular field number (FN) of the utilized light microscope. Performing MC on different areas leads to a non-standardized evaluation and erroneous risk stratification. The aim of the study was to audit real-life MC practices with special emphasis on possible risk stratification errors. A survey was administered to Italian pathologists to evaluate the following: method used for MC (5 mm 2 versus 50 HPF); FN of the light microscope; prognostic scheme for risk stratification. Based on the results of the survey, 100 GISTs (25/risk class using Miettinen prognostic scheme) were retrieved and MC performed using 5 mm 2 versus the corresponding mm 2 area sizes of 50 HPFs with variable FNs (18, 20, 22). The survey demonstrated that the majority of pathologists (64.5%) use 50 HPFs with various FNs leading to excessive area size. The most frequently used prognostic scheme is that by Miettinen. Using this prognostic scheme and counting mitoses in 5 mm 2 versus 50 HPFs with FNs 18, 20 and 22, a change in risk class was identified ranging from 10 to 41%, depending on FN. In conclusion, this study demonstrates that MC is still frequently performed on 50 HPF, with area sizes exceeding the specified 5 mm 2 by far.