Hedieh Honarpisheh

Relationship between hippocampal atrophy and neuropathology markers: a 7T MRI validation study of the EADC-ADNI Harmonized Hippocampal Segmentation Protocol

The pathologic validation of European Alzheimers Disease Consortium Alzheimer’s Disease Neuroimaging Initiative Center Harmonized Hippocampal Segmentation Protocol (HarP).

Comparing hippocampal atrophy in Alzheimer's dementia and Dementia with Lewy Bodies

Background/Aims: Dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD) are the two most common neurodegenerative dementias. During the early stages, clinical distinction between them is often challenging. Our objective is to compare hippocampal atrophy patterns in mild AD and mild DLB. We hypothesized that DLB subjects have milder hippocampal atrophy relative to AD subjects. Methods: We analyzed the T1-weighted magnetic resonance imaging data from 113 subjects: 55 AD, 16 DLB and 42 cognitively normal elderly (normal controls, NC). Using the hippocampal radial distance technique and multiple linear regression, we analyzed the effect of clinical diagnosis on hippocampal radial distance, while adjusting for gender and age. Three-dimensional statistical maps were adjusted for multiple comparisons using permutation-based statistics with a threshold of p < 0.01. Results: Compared to NC, AD exhibited significantly greater atrophy in the cornu ammonis (CA)1, CA2–3 and subicular regions bilaterally while DLB showed left-predominant atrophy in the CA1 region and subiculum. Compared directly, AD and DLB did not reveal statistically significant differences. Conclusion: Hippocampal atrophy, while present in mildly impaired DLB subjects, is less severe than atrophy seen in mildly impaired AD subjects, when compared to NC. Both groups show predominant atrophy of the CA1 subfield and subiculum.

Cytokeratin 20 expression in basaloid follicular hamartoma and infundibulocystic basal cell carcinoma.

Tumors with similar or identical histopathologic features have been termed basaloid follicular hamartoma (BFH) or infundibulocystic basal cell carcinoma (BCC). BCC typically lacks immunoreactivity with cytokeratin 20 (CK20) and pleckstrin homology‐like domain, family A, member 1 protein (PHLDA1).

A Tour of the Thymus: A Review of Thymic Lesions With Radiologic and Pathologic Correlation

The thymus is routinely encountered on cross-sectional imaging studies of the chest. It has a variable appearance, undergoes dynamic changes during periods of stress, and demonstrates numerous different pathologic lesions. Understanding the imaging characteristics of these different lesions facilitates accurate radiographic diagnosis and can prevent unnecessary follow-up imaging and intervention. This article will review normal thymic anatomy and development, thymic hyperplasia and associated medical conditions, and the imaging and pathologic features of various benign and malignant thymic lesions.

Staphylococcal Purpura Fulminans: Report of a Case.

Purpura fulminans (PF) is associated with several infections and most commonly with meningococcemia. However, there are only a few reports of this entity in association with toxic shock syndrome toxin-1-producing Staphylococcus aureus. We report a 53-year-old man who presented with fever, progressive hemodynamic instability, multiorgan failure, and thrombocytopenia following lobectomy for a solitary lung metastasis from rectal adenocarcinoma. He developed progressive generalized eruption of nonblanching red, purple, and black macules, papules, and plaques on the trunk and extremities consistent with PF. He died on postadmission day 3. Autopsy examination revealed purulent pleural exudate, which grew toxic shock syndrome toxin-1-producing S. aureus. Premortem and autopsy skin biopsies demonstrated epidermal necrosis, subepidermal bullae, and fibrin thrombi within small cutaneous vessels with minimal perivascular lymphocytic inflammation and without accompanying vasculitis. With this case report, we would like to draw attention to the fact that staphylococcal toxic shock syndrome-associated PF may be highly underrecognized and much more common than reflected in the literature.

Congenital Melanocytic Nevus of Nipple in a 5‐year‐old Female

Melanocytic lesions of the nipple-areolar region, whether benign or malignant, are extremely rare at any age. Only a single case of congenital melanocytic nevus of nipple has been reported from Austria in a 26-year-old male. Against this background, a congenital nevus of the nipple occurring in 5-year-old girl is described. A 5-year-old female presented with an asymptomatic, 3 9 2 mm, brown, pigmented macule on the left nipple-areolar complex. On physical examination, both breasts and axilla were otherwise unremarkable. The breasts had no evidence of any nodularity or precocious development. More than a year earlier, the patient had had a nevus excised from the back of her scalp at another institution. A biopsy of the left nipple areolar pigmented lesion (Fig. 1a and b) revealed predominantly intraepidermal and a few junctional nests of epitheloid, dyscohesive nevomelanocytes (Fig. 1c–e). These melanocytic nests were associated with focal fusion of the rete ridges (Fig. 1c and d). No pagetoid (single-cell) spread of melanocytes in the epidermis was identified. Deeper levels of the block showed extension of bland nevomelanocytic cells into the sebaceous glands (Fig. 1c, d and f). Two mammary ducts with appropriate level of development for a 5-year-old girl, and immunoreactive for CK7, were present in close proximity of smooth muscle bundles at the edge of the specimen (Fig. 1a and b), confirming the nipple-areolar location of the lesion. The nevomelanocytic cell nests were positive for S100 (Fig. 2a), Melan-A (Fig. 2b), and HMB-45 (Fig. 2c), confirming the melanocytic nature of the cells, but negative for Her2, CK7, and CD68 excluding Paget cells, Toker cells, and histiocytes, respectively. No mitotic figure was identified among the melanocytes. Ki-67 immunostain revealed no positivity in the dyscohesive nest of nevomelanocytes located either in the epidermis or in the sebaceous gland. Based on the morphologic and immunohistochemical findings, a diagnosis of congenital melanocytic nevus of nipple-areolar complex was rendered. Development of melanocytic lesions, benign or malignant, in the nipple-areolar complex is extremely rare in any age group. When this possibility is suggested on the basis of morphology and particularly in patients over 20 years of age, it is important to exclude pigmented histiocytes (melanophages) and Paget cells by using appropriate immunostains— CD68, and CK7/Her2 immunohistochemistry—respectively. Thorough examination of multiple deeper H&E sections to identify bland nevomelanocytes, which are positive for S100, Melan-A, and HMB-45, in the sebaceous lobules or peripheral nerve twigs could provide ironclad evidence for a congenital nevus, and is useful in avoiding diagnostic pitfalls such as melanoma. Primary melanomas are extremely rare in the nipple-areolar region, with only 22 cases reported in the literature since 1947. Address correspondence and reprint requests to: Fattaneh A. Tavassoli, MD, Professor, Department of Pathology, Yale University School of Medicine, PO Box 208023, New Haven, CT 06520-8023, USA, or e-mail: fattaneh. tavassoli@yale.edu

PATHOLOGIC VALIDATION OF THE EADC-ADNI HARMONIZED HIPPOCAMPAL PROTOCOL

monoclonal antibody, in patients with prodromal or mild Alzheimer’s disease (AD). Retrospective analyses of both bapineuzumab and solanezumab data have shown substantially higher percentages of negative amyloid PET findings in APOE ε4 non-carriers than in APOE ε4 carriers in the mild and moderate AD sub-study populations. We report our amyloid PET screening results by APOE ε4 status in the prodromal and mild AD study populations. Methods: During screening, patients fulfilling clinical criteria for either prodromal or mild AD underwent florbetapir PET scanning and APOE genotyping. Florbetapir PET scans were visually evaluated for amyloid plaque burden. Results: Data from the first 250 patients were included in this analysis. Similar to the bapineuzumab and solanezumab results, we have observed a substantially higher percentage of negative amyloid PET findings in APOE ε4 non-carriers than in APOE ε4 carriers (highlighted in bold in Table 1). However, the overall incidence of negative amyloid scans observed in 221AD103 is substantially higher than that reported in the two Phase III studies, likely attributable to the earlier stage of AD patients being recruited in this study (prodromal/mild, mean MMSE w 25 vs. mild/moderate AD, mean MMSE w21 in the Phase III studies). This finding is also consistent with the solanezumab results in that the percentage of negative amyloid PET findings was higher in mild (27%) than in moderate (13%) AD groups. Conclusions: These results suggest that: (1) selecting subjects having AD pathology based on clinical criteria remains a challenge; (2) enrichment by using amyloid PET imaging is effective and feasible; (3) enrichment by assessing amyloid plaque burden is critically important to clinical studies in early stages of AD because of a higher incidence of negative amyloid findings; and (4) APOE genotyping may potentially improve the economy of enrichment by amyloid PET, via lowering the likelihood of negative amyloid findings.

PATHOLOGIC VALIDATION OF THE HIPPOCAMPAL RADIAL DISTANCE SURFACE MAPPING TECHNIQUE

calculated using multiple algorithms. Algorithms included FreeSurfer/ReconAll/longitudinal v5.3.0, FSL/FIRST v5.0.4, AdaBoost, manual, multiple-atlas propagation and segmentation (MAPS) and MAPS with the hippocampal boundary shift integral option (MAPS-HBSI) (Leung et al. NeuroImage 2010;51:1345-1359). The difference between the PVC’s (non annualized) was calculated (BTBD). To compare the performance of any two algorithms, the absolute values of the BTBD for each subject were compared and the algorithm with the smallest absolute BTBDs was considered superior. Results: MAPS-HBSI had substantially better reproducibilities than all other algorithms. MAPS-HBSI had smaller absolute BTBD for the left hippocampus in 0.69 (FreeSurfer), 0.71 (FIRST), 0.72 (AdaBoost), 0.68 (manual), 0.81 (MAPS) fraction of subjects, all which had a p-value smaller than 0.002. The median absolute value of the BTBD (MAVBTBD) were 2.36 (FreeSurfer), 2.19 (FIRST), 2.61 (AdaBoost), 2.75 (manual), 3.41 (MAPS) and 1.29 (MAPS-HBSI). Previous comparisons of algorithm performances have often been based on a particular disease, such as AD, that can introduce confounding factors including natural disease variation and measurement error in disease classification. For example, previous assessments of the BSI option, based on AD group size (Leung et al. 2010), is 47% much less than the 164% found in this study. Conclusions: MAPS-HBSI has 70% better reproducibility than the nearest other hippocampal PVC algorithms due to the BSI option. The performance for BSI is 79% better than previously reported perhaps because of the disease independent assessment of the current study. The high reproducibility of MAPS-HBSI makes it much easier to compare the PVC of the left and right hippocampus for individual subjects and study the PVC variation in AD.