Clinical-pathological Correlation Research Articles

The Adult Changes in Thought (ACT) Medical Records Abstraction Project: A Resource for Research on Biological, Psychosocial and Behavioral Factors on the Aging Brain and Alzheimer’s Disease and Related Dementias

Background: Adult Changes in Thought (ACT), a prospective cohort study, enrolls older adult members of Kaiser Permanente Washington. We describe an ambitious project to abstract medical records facilitating epidemiological investigation. Methods: Abstracted data include medications; laboratory results; women’s health; blood pressure; physical injuries; cardiovascular, neurological, psychiatric and other medical conditions. Results: Of 1419 of 5763 participants with completed abstractions, 1387 (97.7%) were deceased; 602 (42.4%) were diagnosed with Alzheimer’s Disease and Related Dementias; 985 (69.4%) had a brain autopsy. Each participant had an average of 34.3 (SD = 13.4) years of data abstracted. Over 64% had pharmacy data preceding 1977; 87.5% had laboratory data preceding 1988. Stroke, anxiety, depression and confusion during hospitalization were common among participants diagnosed with dementia. Conclusions: Medical records are transformed into data for analyses with outcomes derived from other ACT data. We provide detailed, unparalleled longitudinal clinical data to support a variety of epidemiological research on clinical-pathological correlations.

Discordance of human epidermal growth factor receptor 2-low status between breast primary and distant metastases with clinical-pathological correlation.

Breast cancer with human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) 1+ or 2+ with negative in-situ hybridisation (ISH) (HER2-low) can now be targeted by HER2 antibody drug conjugates. We set out to compare HER2 status between matched primary invasive breast carcinoma (IBC) and distant metastases (DM) with clinical-pathological correlation, with specific interest in HER2-low. Biomarker studies and clinical-pathological features of primary IBC with matched DM diagnosed between 2021 and 2022 were retrospectively analysed. HER2 status was assessed per 2023 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines for IHC (4B5) and ISH (IQFISH pharmDX). Bilateral breast primaries were excluded. HER2 IHC 0 to 1+ were reassessed. One hundred and forty-seven cases of primary IBC with matched DM were identified. Biomarkers were performed on core biopsy (n = 74) and resection (n = 73). One hundred and twenty-six (86%) were initially classified as 'HER2-negative'; of these, 67 (46%) were reclassified as HER2-low. Patients with HER2-positive primaries were younger (P = 0.01) and had an increased incidence of micropapillary carcinoma (P = 0.02). HER2-low primaries also had an increased incidence of micropapillary carcinoma (P = 0.02) and oestrogen receptor (ER) positivity (P = 0.02) compared to HER2 0. One hundred and sixty-nine matched DM cases excluding bone metastasis were identified (range = one to seven metastases per IBC). The most common sites of metastases were liver (50 of 169, 30%), lung (36 of 169; 21%), distant lymph node (26 of 169, 15%); 138 DM cases (82%) were previously classified as 'HER2-negative', and 62 (37%) were reclassified as HER2-low. Like HER2-low primaries, HER2-low metastases were frequently ER-positive (52 of 62; 84%) (P = 0.02). Brain metastases were more frequently HER2-positive (five of 32; 16%) (P = 0.04). Comparing HER2 status in matched primaries and DM, HER2 status was discordant in 62 cases (37%). Most changes occurred from HER2-low to HER2 0 (33 of 169, 20%), HER2 0 to HER2-low (17 of 169, 10%) and HER2-low to positive (10 of 169, 6%). All HER2-low to HER2 0 changes were HER2 1+ to 0. In 30 patients with multiple DM sites (47 cases), HER2 status among different DM samples was discordant in 16 patients (53%), mainly from HER2-low to HER2 0 (16 of 47, 34%). A significant proportion of previous 'HER2-negative' primaries and DM cases were reclassified as HER2-low. Discordant HER2 status between IBC primary and metastasis and between different DM sites demonstrated tumour heterogeneity and highlights the need for HER2 retesting in distant metastasis.

A long gestation: spine anatomy from the medieval age to the end of the 19th century. An analytical historical review.

The discovery of spine anatomy followed a problem/solution pattern; it took almost 1000 years to transition from nihilism to perfectionism. Before the 16th century, the main issue was accessing and opening the spine. The level of knowledge progressed rapidly when the spinal canal was opened longitudinally during the 16th century. The 17th century was an incubation period that allowed the consolidation of the science of anatomy with the help of art, philosophy, and other sciences. In particular, the conservation of the cadaver was improved. Famous spine anatomists were close to Rembrandt, master of the chiaroscuro technique, which helped to improve the anatomical drawings significantly. Descriptions of the pathological anatomy of the spine were first published early in the 17th century, but progress was slow up to the end of the 18th century due to a lack of occasions for clinical-pathological correlations. Normal anatomy became remarkably accurate in the 18th and 19th centuries when soft tissues and connections (e.g., among the intervertebral discs) were studied in detail. The slow compressions due to underlying diseases and then the degenerative processes were subsequently described.

A single-center retrospective review of metastatic prostate cancer on PSMA position emission tomography/computed tomography: Beyond lymph nodes and bones.

Prostate-specific membrane antigen (PSMA) Positron emission tomography/computed tomography (PET/CT) has become a crucial imaging modality for the staging of patients with prostate cancer. The purpose of this study is to retrospectively determine the frequency, anatomical distribution, and clinical-pathologic correlates of extra-nodal and extra-osseous metastatic prostate cancer detected on PSMA PET/CT. All available 650 PSMA PET/CT performed in patients with biopsy-proved prostate cancer in our institution between September 2021 and December 2023 were reviewed for the presence of extra-nodal and extra-osseous metastatic disease (M1C disease). Thirty-four patients with M1C disease were identified. The most frequent sites of visceral/soft tissue metastases were the lungs (58.8%), liver (23.5%) and adrenal glands (20.6%). 75% of patients with lung metastases detected on PSMA PET/CT had concurrent intrathoracic lymph node involvement. A higher frequency of patients with M1C disease (55.9%) had a high Gleason score. The median prostate-specific antigen (PSA) level at the time of the PSMA scan was 20.16 ng/mL. There was a statistically significant association between PSA level and osseous disease (p = 0.004), as well as PSA level and nodal disease (p = 0.008). While a large number of patients had concurrent osseous and nodal disease (82.4% and 79.4%, respectively), no visceral/soft tissue sites demonstrated a significant association with the presence of osseous or nodal involvement. Given the increasing utilization of PSMA PET/CT, increased knowledge of the location and pattern of distribution of visceral/soft tissue metastatic sites is crucial not only for staging but also to better understand patterns of therapeutic response. We identified the lungs, liver and adrenal glands as the most common visceral/soft tissue metastatic sites from prostate cancer. We found that higher PSA levels at the time of PSMA PET/CT imaging were positively associated with concurrent osseous and nodal involvement.

Clinical-pathological correlation of endoscopic findings in eosinophilic esophagitis in the pediatric population.

Eosinophilic esophagitis (EoE) is an immunologic disorder of the esophagus with an increasing incidence in our region of 8.1 cases per 100,000 inhabitants per year. It is characterized by dysphagia, and its diagnosis requires esophagoscopy with biopsies for histopathological analysis, which macroscopically reveals certain characteristic endoscopic findings, though their diagnostic utility remains uncertain. The correlation between these endoscopic findings and the histopathological diagnosis of EoE continues to be a subject of controversy in the pediatric population. This study evaluates the clinical-pathological association of different endoscopic abnormalities in EoE. We conducted an analytical study of patients under 15 years old who underwent esophagoscopy due to highly suspicious symptoms of EoE at a pediatric hospital between 2015 and 2022.

Multicentric reticulohistiocytosis with oral and laryngeal involvement in association with autoimmune/inflammatory syndrome induced by adjuvants (ASIA): expanding the spectrum of two uncommon entities.

Multicentric reticulohistiocytosis (MRH) is the most frequent entity in the group of reticulohistiocytoses. It is usually accompanied by a symmetrical erosive polyarthritis and is frequently associated with cancer and autoimmune disorders. Autoimmune syndrome induced by adjuvants (ASIA) is an inflammatory syndrome triggered by adjuvants such as those contained in vaccines or by silicone implants. Here we report a 71-years old female with a history of breast cancer treated with surgery and subsequent prosthesis who developed a systemic hyperinflammatory syndrome including seronegative symmetric polyarthritis, multiple skin lesions and two large nodular lesions in the oral cavity and larynx. Clinical picture was consistent with a clinical diagnosis of ASIA, with breast implant rupture and/or vaccination against SARS-CoV-2 as possible triggers. Histopathology of skin, oral and laryngeal nodules revealed cutaneous/mucous and submucosal infiltration of large epithelioid mononuclear or binucleated cells with fine granular ground glass-like cytoplasm and round to kidney-shaped nuclei with prominent nucleoli, without atypical features or relevant pleomorphism, accompanied by sparse giant cells and lymphocytes. These cells stained positive for CD68 and CD45 and negative for S100, CD1a, and markers of epithelial or neural/melanocytic differentiation, altogether consistent with a diagnosis of reticulohistiocytosis. Clinic-pathological correlation allowed the final diagnosis of MRH. To our knowledge, this is the first report of a co-occurrence of MRH with ASIA and this is relevant to broaden the spectrum of those both rare diseases.

Clinical Pathological and Immunohistochemical Correlations in Gastric Cancer.

Due to its high aggressiveness and polyclonal tumor state, stomach cancer is considered a severe health problem. In this study, we analyzed Her2 and Ki67 in correlation with patient data for the possibility of prognostic factors. The study included 48 cases of gastric tumors that had been surgically treated in a period of five years. The percentage was statistically significant for intestinal-type adenocarcinomas located in the medio-gastric region (p = 0.05); in the diffuse subtype, there were no Her2 positive samples, and in the mixed subtype only one out of three samples was Her2 positive. Our results confirm the existing data, and we can conclude that this link can be considered a prognostic factor in the progression and treatment effectiveness.

When mycosis fungoides seems not to be within the spectrum of clinical and histopathological differential diagnoses.

The most prevalent primary cutaneous T-cell lymphoma, mycosis fungoides (MF), is characterized by the development of plaques and nodules after an erythematous patchy phase that is non-specific. An infiltrate of atypical small- to medium-sized cerebriform lymphocytes in the superficial dermis, with variable epidermotropism, is the histopathological hallmark of the disease. In more advanced stages of the illness, large-cell transformation may be seen. Early diagnosis of MF can be very challenging based only on histopathologic or clinical findings, so it is critical to have a clinical-pathological correlation. Many atypical variants of MF that deviate from the classic Alibert-Bazin presentation of the disease have been described over the past 30 years, sometimes with different prognostic and therapeutic implications. Clinically or histopathologically, they can mimic a wide range of benign inflammatory skin disorders. To make a conclusive diagnosis in these cases, it is recommended to take multiple biopsies from various lesions and to carefully correlate the clinical and pathological findings. We have outlined the various facets of the illness in this review, positioning MF as a "great imitator", with an emphasis on the more recently identified variations, differential diagnosis, and its benign mimics.

Paediatric onset lymphomatoid papulosis: results of a multicentre retrospective cohort study, on behalf of the EORTC Cutaneous Lymphoma Tumours Group (CLTG).

Lymphomatoid Papulosis (LyP) is a rare cutaneous T-cell lymphoproliferative disorder. Comprehensive data on LyP in the paediatric population is scarce. To characterize epidemiological, clinical, histopathological, and prognostic features of paediatric LyP. This was a retrospective, multicentre international cohort study including 87 cases of children and adolescents with LyP diagnosed between 1998 and 2022. Patients aged ≤ 18 years old at disease onset were included. Diagnosis was made in each centre based on clinical-pathological correlation. Eighty-seven patients from 12 centres were included. The mean age at onset was 7.0 years (range 3 months-18 years) with a male to female ratio of 2:1. The mean time between onset of first cutaneous lesions and diagnosis was 1.3 years (range 0-14 years). Initial misdiagnosis concerned 26.4% of patients. Initially, LyP was most often misdiagnosed as Pityriasis lichenoides et varioliformis acuta (PLEVA), insect bites, or mollusca contagiosa. Erythematous papules or papulonodules were the most frequent clinical presentation. Pruritus was specifically mentioned for 20.7% of patients. The main histological subtype was type A in 55.1% of the cases. If analysed, monoclonal TCR rearrangement was found in 76.5% of the skin biopsies. The overall survival rate was 100% with follow up at 5 years available for 33 patients and at 15 years for 8 patients. A development of associated haematological malignancy (HM) occurred in 9.6% of the cases (7/73), including four mycosis fungoides (MF) cases, one primary cutaneous anaplastic large cell lymphoma (pc-ALCL), one systemic ALCL and one case of acute myeloid leukaemia. If we compare incidence rates of cancer with the world 0-19 years old population from 2001-2010, we estimate a significantly higher risk of associated malignancy in general, occurring before the age of 19 years old with incidence rate ratio of 87.49 (CI 86.01-88.99). We report epidemiological data from a large international cohort of children and adolescents with LyP. Overall the prognosis of the disease is good, with excellent survival rates for all patients. Due to increased risk of associated HM, a long-term follow-up should be recommended for LyP patients.

Clinical-pathological Correlation of CD68 and CD8 in Tumor Immune Microenvironment of Salivary Gland Neoplasms

Clinical-pathological Correlation of CD68 and CD8 in Tumor Immune Microenvironment of Salivary Gland Neoplasms

Abstract 5048: NF2 mutations are enriched in FH deficient renal cell cancer

Abstract Introduction: NF2 is a tumor suppressor gene in charge of producing a protein called Merlin that controls cell growth and division. Mutations in the NF2 gene affect predominantly the nervous system causing the development of benign tumors. NF2 mutations have been reported in Renal cancers with morphologically specific tumor types and in aggressive tumors. We studied a cohort of 16 cases of RCC in which the NF2 mutation was identified and describe other molecular changes as well as morphology and clinic-pathological correlation. Materials and Methods: Sixteen patients had been consented and treated for renal masses in protocols of the UOB division of the NCI. Next generation sequencing was performed with tumor DNA from FFPE tissue using the Illumina TruSight Oncology 500 Kit (TSO500) NextSeq 550DX. TSO500 assay was designed to detect single nucleotide variations, small insertions/deletions, copy number variations from 92 genes, TMB and MSI. Morphology and IHC stains were performed. Results: Nine patients were female and 7 males, ranging in age from 21 to 87 years. Fourteen patients underwent partial or total nephrectomies, one case had a biopsy and in 1 case a metastatic tumor to a lymph node was studied. Morphologically, nine cases were diagnosed as HLRCC, three clear cells, two cases with clear and papillary cell, one medullary and one oncocytoma. Genetic findings revealed mutations in NF2, FH,VHL, SMARCB1, HOBB13, ARID1B, B2M, EP300, BCORL1 and MGA. Concurrent coexistence of NF2 and FH mutations was present in 9 cases. Three patients with concurrent FH and NF2 mutations died of the disease. Conclusions: NF2 mutations have been identified in a variety of morphologic types of Renal cell cancer. However, we were surprised by the number of cases with NF2 mutation in tumors that also harbor the FH (HLRCC) mutation. NF2 tumors have been reported to have an aggressive behavior, and FH cancers are also known to have poor survival. Genomic studies of renal cancers is recommended since some genetic alterations are targetable and may provide adequate therapies that will lead to longer survivals. Citation Format: Khaled Bin Satter, Liqian Xi, Christopher Rickets, William M. Linehan, Maria J. Merino. NF2 mutations are enriched in FH deficient renal cell cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5048.

Diagnostic Imaging of Agminated Blue Lesions and Blue Lesions with Satellitosis: Case Series with a Concise Review of the Current Literature

Background: Agmination and/or satellitosis in pigmented blue lesions is a phenomenon rarely mentioned in the literature and not well known. This phenomenon can be expressed by several benign and malignant pigmented blue lesions, such as blue nevi, Spitz nevi, melanocytoma and melanoma. On this spectrum, dermoscopy, reflectance confocal microscopy (RCM) and dynamic Optical coherence tomography (D-OCT) represent non-invasive imaging technologies, which may help clinicians in the diagnosis of melanoma and non-melanoma skin cancers in daily clinical practice. Methods: Currently, in the literature there is a lack of new data about agminated blue lesions and blues lesions with satellitosis, as well as the lack of a recent and updated review of the literature about this topic. Therefore, considering that clinicians must be confident with the diagnosis of these rare skin lesions, we decided to carry out this work. Results: In this paper, four new cases of agminated pigmented cutaneous lesions were described. Moreover, a review of the current literature on this topic was performed. Conclusions: A clinical–pathological correlation is often needed to reach a correct diagnosis; currently, dermoscopy and non-invasive diagnostic techniques, such as reflectance confocal microscopy and optical coherence tomography, due to the depth of these skin lesions in the dermis, can only make a partial and limited contribution.

The value of diagnostic vitrectomy: Histocytopathology techniques for the diagnosis of lymphoma of the retina

Abstract Purpose: Primary large B-cell lymphoma of the retina, vitreous, and central nervous system (CNS), is an intraocular tumor with an unspecific and insidious clinical presentation. Pars plana vitrectomy (PPV) and optical coherence tomography (OCT) are useful diagnostic tools for this malignant process. The aim of this study is to evaluate the diagnostic efficacy of PPV for these intraocular lesions under a modified diagnostic protocol with a clinical pathological correlation with OCT imaging. Materials and Methods: A total of 115 samples were collected after a vitrectomy procedure (aspiration or vitrectomy cassette). The samples were centrifuged, and the precipitates were collected. A cell block was prepared and analyzed with multiple stains and an immunohistochemistry (IHC) panel, including B- and T-cell markers, as well as light chain markers, to establish the monoclonal nature of the tumor. Of the 115 samples, 9 (7.83%) were diagnosed with large B-cell lymphoma of the retina, vitreous, and CNS. Conclusion: Diagnostic vitrectomies for the large B-cell lymphoma of the retina, vitreous, and CNS is an excellent tool for the diagnosis of this entity. A negative diagnostic PPV with a strong suspicious OCT image, where the neoplastic cells are located between the retinal pigmented epithelium and Bruch’s membrane, the latter procedure should be either repeated or a chorioretinal biopsy be performed. In contrast, a positive vitrectomy using the IHC panel for large B-cell lymphoma of the retina, vitreous, and CNS is pathognomonic of this condition. In addition, the OCT is an important tool to help in the diagnosis of this difficult entity. Results: The diagnostic PPV provided suitable vitreous samples to all patients with undetermined uveitis and/or intraocular tumor suspicion. A morphological and immunohistichemical (IHC) analysis enabled a conclusive diagnosis of retina, vitreous and CNS lymphoma in all patients submitted to the procedure.

Clinical-pathological correlation of various symptoms in the diagnosis of pediatric eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is an immune-mediated disorder of the esophagus with a broad spectrum of clinical presentations. Dysphagia and food impaction are the cardinal symptoms; however, their diagnostic utility remains controversial in pediatric populations. This study evaluates the clinical-pathological association of different symptoms with EoE. We conducted an analytical study of patients under 15 years of age who underwent esophagoscopy at a pediatric hospital between 2015 and 2022 due to suspected EoE (Reg. 341E/2023). The prevalence of various symptoms and medical histories was compared, along with their association with histopathological abnormalities, between patients with EoE and those without the disease (NEoE). A total of 24 EoE patients and 17 NEoE children were included.

Evaluation of cervical cytological abnormalities in correlation with clinical findings in Iraqi patients

Abstract Objective: Many articles study the efficiency of pap smears in detecting cervical disease and precancerous lesions; however, in Iraq, only few researches study the clinic-pathological correlation in pap smear results. In this study, we will highlight the correlation of pap smears with the most important and frequent clinical data and findings on cervical examination. Materials and Methods: One hundred and twenty cases are collected from private clinics of gynecology in Al-Kut province during the interval (June 1, 2020, to February 28, 2021). Clinical history was obtained and pap smear test was examined by two pathologists. Data were analyzed using SPSS software program version 26. Results: There were significant statistical association between cytological abnormalities on pap smear test and age of the patient (P-value of 0.01), with low grade squamous intraepithelial lesion (LSIL) result showed the highest mean age of 46.91 as well as significant association with a number of live birth and a number of pregnancies with significant P value (<0.001 and <0.001) in the same order. Atypical squamous cells of undetermined significance were the most common cytological abnormality. Conclusion: Women should not delay their first screening pap test for more than 30 years of age since the mean age for LSIL (the most significant abnormality present in this study) was the age of 46. 91 ± 10.75. awareness about screening for cervical precancerous lesions should be increased especially among multiparous women and those more than 40 years of age.

Clinical Manifestations.

It is unclear whether primary progressive apraxia of speech (PPAOS) and progressive agrammatic aphasia (PAA) represent the two ends of a clinical continuum or exist as distinct syndromic entities with specific pathologic/prognostic correlates. We aimed to characterize the main clinical features along the spectrum of progressive non-fluent speech-language disorders (nf-SLD) and explore the existence of data-driven symptom clusters with etiological/prognostic value. We included 98 participants presenting with progressive motor speech impairment and/or agrammatism, of which 43 had an autopsy-confirmed neuropathological diagnosis. Speech pathologists rated motor speech features indicative of dysarthria and AOS. Quantitative measures of expressive/receptive agrammatism were obtained and compared with healthy controls. Baseline and longitudinal disease severity was assessed with the Clinical Dementia Rating sum-of-boxes (CDR-SB). We explored the clustering tendency of the data to form robust symptom clusters and used principal component analysis to extract data-driven clinical components. The longitudinal CDR-SB change was estimated with linear mixed-effects models. Ninety-one participants fitted previously reported clinical profiles (69 AOS+agrammatism, 18 PPAOS and 4 PAA), while 7 remained unclassifiable and were characterized by nonfluent speech and dysarthria in the absence of apraxia of speech or agrammatism. None of the baseline clinical features discriminated between FTLD subgroups. The Hopkins statistic ruled out the existence of syndromic clusters in the whole sample. Three data-driven components explained 71% of the variance ([i]severity-agrammatism, [ii]AOS, and [iii]dysarthria). The component characterized by prominent dysarthria was more specific to patients with Progressive Supranuclear Palsy while the component characterized by severity-agrammatism predicted a faster CDR-SB increase. Our results suggest that nf-SLD represents a clinical continuum. Splitting this continuum into different clinical phenotypes based on its major clinical features does not improve clinical-pathological correlations, stressing the need for new clinical and biological markers. The term nf-SLD could be used to group together these speech-language phenotypes strongly associated with FTLD.

Peripheral vascular emergencies-clinicopathological co- relation with outcome in a tertiary care centre

Background: Peripheral arterial disease represents a major caseload in emergency department and also is major cause of distress and socio-economic burden to patient and his/her family due to risk of complications. It has a multifactorial etilogy and requires prompt treatment to salvage the limb and prevent complications. This study is a clinic-pathological correlation between various factors and surgical outcome. Methods: It is a prospective study involving 75 patients who had presented with peripheral vascular disease with different mode of presentations. All patients underwent surgical procedure and were given inj. heparin and tab. Aspirin in post operative period. Their surgical outcome was studied and co-related with etiological factors and clinical presentation. Result: Time from onset till presentation was one of the most important factors in deciding outcome. COVID-19 also emerged as one of the important risk factors in 12 cases. Patients who had been given prior anticoagulation therapy had better outcomes. Conclusions: Outcome in peripheral vascular disease patient depends on variable factors, however starting patients prior on anticoagulants has shown more possibility of salvaging the limb.

Clinical dimensions along the non-fluent variant primary progressive aphasia spectrum.

It is debated whether primary progressive apraxia of speech (PPAOS) and progressive agrammatic aphasia (PAA) belong to the same clinical spectrum, traditionally termed non-fluent/agrammatic variant primary progressive aphasia (nfvPPA), or exist as two completely distinct syndromic entities with specific pathologic/prognostic correlates. We analysed speech, language and disease severity features in a comprehensive cohort of patients with progressive motor speech impairment and/or agrammatism to ascertain evidence of naturally occurring, clinically meaningful non-overlapping syndromic entities (e.g. PPAOS and PAA) in our data. We also assessed if data-driven latent clinical dimensions with aetiologic/prognostic value could be identified. We included 98 participants, 43 of whom had an autopsy-confirmed neuropathological diagnosis. Speech pathologists assessed motor speech features indicative of dysarthria and apraxia of speech (AOS). Quantitative expressive/receptive agrammatism measures were obtained and compared with healthy controls. Baseline and longitudinal disease severity was evaluated using the Clinical Dementia Rating Sum of Boxes (CDR-SB). We investigated the data's clustering tendency and cluster stability to form robust symptom clusters and employed principal component analysis to extract data-driven latent clinical dimensions (LCD). The longitudinal CDR-SB change was estimated using linear mixed-effects models. Of the participants included in this study, 93 conformed to previously reported clinical profiles (75 with AOS and agrammatism, 12 PPAOS and six PAA). The remaining five participants were characterized by non-fluent speech, executive dysfunction and dysarthria without apraxia of speech or frank agrammatism. No baseline clinical features differentiated between frontotemporal lobar degeneration neuropathological subgroups. The Hopkins statistic demonstrated a low cluster tendency in the entire sample (0.45 with values near 0.5 indicating random data). Cluster stability analyses showed that only two robust subgroups (differing in agrammatism, executive dysfunction and overall disease severity) could be identified. Three data-driven components accounted for 71% of the variance [(i) severity-agrammatism; (ii) prominent AOS; and (iii) prominent dysarthria]. None of these data-driven LCDs allowed an accurate prediction of neuropathology. The severity-agrammatism component was an independent predictor of a faster CDR-SB increase in all the participants. Higher dysarthria severity, reduced words per minute and expressive and receptive agrammatism severity at baseline independently predicted accelerated disease progression. Our findings indicate that PPAOS and PAA, rather than exist as completely distinct syndromic entities, constitute a clinical continuum. In our cohort, splitting the nfvPPA spectrum into separate clinical phenotypes did not improve clinical-pathological correlations, stressing the need for new biological markers and consensus regarding updated terminology and clinical classification.

PPY-cell hyperplasia accompanying NENs: Immunohistochemical and nuclear medicine analysis

Pancreatic polypeptide cell hyperplasia (PPY-H) is a multiplication of the neuroendocrine cells producing pancreatic polypeptide (PPY). The development and role of PPY-H and its corresponding clinical and imaging findings still need to be fully elucidated. We present 12 cases of PPY-H accompanying pancreatic neuroendocrine neoplasias (NEN). PPY-H was analyzed with the help of immunohistochemistry and confocal microscopy; preoperative clinical data and imaging studies were evaluated retrospectively. We observed PPY-H emerging from pancreatic ducts, and in some cases, we observed simultaneous NKX6.1 positivity in ducts and PPY-H. Additional clinical-pathological correlations suggests that gastrointestinal symptoms (e.g., epigastric pain and cholestasis) could be more related to PPY-H than to NEN hormonal production. In particular cases, SSTR2 expression was strong in PPY-H and correlated with distinguishable accumulation of activity next to NEN on 99 mTc EDDA/Hynic-TOC SPECT/CT. In another case, 18F-FDG-PET/CT showed increased metabolic activity in the area of PPY-H surrounding NEN. Our data suggest that PPY-H originates in the lining of pancreatic ducts. Confirmation of SSTR2 in PPY-H, using immunohistochemistry, suggests the utility of 99 mTc EDDA/Hynic-TOC or 68Ga-DOTA radiotracers in clinical diagnostics; however, studies with larger cohort are needed.

Sympathetic Ophthalmia in Patients with Enucleation or Evisceration: Pathology Laboratory and IRIS® Registry Experience

Introduction: Sympathetic ophthalmia (SO) is a rare bilateral granulomatous panuveitis that can follow surgical or nonsurgical ocular trauma in one eye. Because its diagnosis requires clinical-pathologic correlation, the true incidence of SO is unknown, and there is a need to understand the recent trends in risk factors and frequency of this condition. Methods: Pathology records of all enucleated or eviscerated (ENEV) eyes at three pathology laboratories were reviewed. Data collected included patient demographics, procedure indication, pathology diagnosis, and clinical history of trauma and uveitis. IRIS® Registry (Intelligent Research in Sight) was searched for all patients with SO, acquired absence of eye (AAE), and/or ENEV. Data obtained included patient demographics, ocular procedures, and preoperative diagnoses within 30 days of AAE/ENEV. Results: In the pathology laboratory setting, the incidence of SO over a 36-year period in patients who underwent ENEV was 0.2% (20/9,092); the 5-year incidence ranged from 0.0 to 0.3%. Among the 20 eyes with SO, the inciting event was surgical trauma in 50% (10/20), nonsurgical trauma in 45% (9/20), and missing/undetermined in 5% (1/20). SO was suspected preoperatively in 7/20 (35%) patients. Clinical concern for SO and ruptured globe were indications for ENEV in 50/9,092 (0.5%) and 872/9,092 (10%) patients, respectively. In the IRIS Registry, 0.7% (199/27,830) of patients with AAE/ENEV had diagnosis of SO. The frequency of SO between 2015 and 2020 was 0.01% (7,371/62,318,249); of these 7,371 cases, 199 (3%) had AAE/ENEV. In 25,975 patients with available data, injury and SO were listed as diagnoses less than 30 days prior to AAE/ENEV in 909 (4%) and 63 (0.2%) cases, respectively. Conclusion: The frequency of SO in recent decades has been low. Most cases of SO are not managed with eye removal. In histopathology-confirmed SO, surgical trauma is as frequent as nonsurgical trauma as an inciting etiology of disease.