A case of necrotizing fasciitis of the orbit secondary to Aspergillus fumigatus and mixed flora.

A 79-year-old female presented to the emergency department for sudden-onset ocular pain, edema, and erythema around her left eye. She also had a left-sided migraine and frontal fullness for 2 weeks. She had attentive care for the diagnosis of orbital cellulitis and prompt recognition of necrotizing fasciitis. Wound cultures were positive for over 5 strains of bacteria in addition to Aspergillus. In a combined effort by our institution's Ophthalmology and Otolaryngology departments, the patient was successfully treated with debridement, porcine bladder matrix, antibiotics, and antifungals. The authors describe the first reported case of eyelid and periorbital necrotizing fasciitis, caused by mixed flora and Aspergillus fumigatus, that showed promising wound healing with the outlined treatment paradigm.

Cytological features of cranial and paraspinal nerve Tumours.

The 2021 World Health Organization Classification of Central Nervous System Tumours introduced significant revisions to the categorization of paraspinal and nerve sheath tumours. This updated system encompasses seven tumour types: schwannoma, neurofibroma, perineurioma, hybrid nerve sheath tumours, malignant melanotic nerve sheath tumour, malignant peripheral nerve sheath tumour and cauda equina neuroendocrine tumour. This review provides an image-rich cytologic reference of these tumours, with particular emphasis on intraoperative smear preparations. Knowledge of the key cytological features of these tumours and their differential diagnoses will help guide classification of these challenging entities.

Performance of a condensed protocol to assess limbic-predominant age-related TDP-43 encephalopathy neuropathologic change.

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is a dementia-related proteinopathy common in the elderly population. LATE-NC stages 2 or 3 are consistently associated with cognitive impairment. A condensed protocol (CP) for the assessment of Alzheimer disease neuropathologic change and other disorders associated with cognitive impairment, recommended sampling of small brain portions from specific neuroanatomic regions that were consolidated, resulting in significant cost reduction. Formal evaluation of the CP for LATE-NC staging was not previously performed. Here, we determined the ability of the CP to identify LATE-NC stages 2 or 3. Forty brains donated to the University of Washington BioRepository and Integrated Neuropathology laboratory with known LATE-NC status were resampled. Slides containing brain regions required for LATE-NC staging were immunostained for phospho-TDP-43 and reviewed by 6 neuropathologists blinded to original LATE-NC diagnosis. Overall group performance distinguishing between LATE-NC stages 0-1 and 2-3 was 85% (confidence interval [CI]: 75%-92%). We also used the CP to evaluate LATE-NC in a hospital autopsy cohort, in which LATE-NC was more common in individuals with a history of cognitive impairment, older age, and/or comorbid hippocampal sclerosis. This study shows that the CP can effectively discriminate higher stages of LATE-NC from low or no LATE-NC and that it can be successfully applied in clinical practice using a single tissue block and immunostain.

Donor-Derived Neuroendocrine Carcinoma Transmission to Two Kidney Transplant Recipients Demonstrated by Short Tandem Repeat Analysis: A Case Report.

Cancer transmission from a donor organ to a transplant recipient is a rare but not infrequently fatal event. We report a case of lung cancer transmission from a deceased donor to 2 kidney recipients. Approximately 1 year after uneventful kidney transplantation, both recipients developed acute kidney failure. Computed tomography imaging of abdomen and pelvis for both recipients showed masses in the transplanted kidneys along with innumerable masses in the livers. Pathologic examinations for both cases demonstrated high-grade neuroendocrine carcinoma with "mirror image" histologic findings in the transplant kidneys with liver metastases. Short tandem repeat (STR) analyses were performed to determine the origin of the tumors. STRs of both tumors were nearly identical to that of the donor, proving that both tumors were from the same donor. Immunohistochemical analyses showed that both tumors were positive for thyroid transcription factor 1, supporting a lung primary. One recipient died as a direct sequela to metastatic tumor, and the other required transplant nephrectomy and chemotherapy. Awareness of this largely nonpreventable complication and prompt molecular testing if cancer transmission is suspected are important.

Endometrial Adenocarcinomas With No Specific Molecular Profile: Morphologic Features and Molecular Alterations of "Copy-number Low" Tumors.

The study evaluated morphologic patterns, mutational profiles, and ß-catenin immunohistochemistry (IHC) in copy-number low (CNL) endometrial adenocarcinomas (EAs). CNL EAs (n=19) with next-generation or whole genome sequencing results and available tissue for IHC were identified from our institutional database. Clinical data and histologic slides were reviewed. IHC for ß-catenin was performed and correlated with mutation status. Images of digital slides of CNL EAs from The Cancer Genome Atlas (TCGA) database (n=90) were blindly reviewed by 4 pathologists, and morphology was correlated with mutation status. Categorical variables were analyzed using the Fisher exact test, and agreement was assessed using Fleiss κ. CTNNB1 mutations were present in 63% (12/19) of CNL EAs. ß-catenin nuclear localization was present in 83% of CTNNB1-mutated tumors (10/12) and in 0% (0/7) of CTNNB1-wildtype tumors (sensitivity 0.83, specificity 1.00). Squamous differentiation (SD) was present in 47% (9/19) and was more often observed in CTNNB1-mutated tumors (P=0.02). Mucinous differentiation (MD) was associated with KRAS mutations (P<0.01). Digital image review of TCGA CNL EAs revealed that pathologist agreement on SD was strong (κ=0.82), whereas agreement on MD was weak (κ=0.48). Pathologists identified SD in 22% (20/90), which was significantly associated with the presence of CTNNB1 mutations (P<0.01). CNL EAs demonstrate several morphologies with divergent molecular profiles. SD was significantly associated with CTNNB1 mutations and nuclear localization of ß-catenin in these tumors. Nuclear expression of ß-catenin is a sensitive and specific IHC marker for CTNNB1 mutations in CNL EAs. CNL EAs with KRAS mutations often displayed MD.

Defying Occam's Razor: Colonic Luminal Endometriosis in an Adolescent With Crohn's Disease.

Abdominal pain is a common symptom in Crohn's disease, presumably associated with mucosal inflammation and/or luminal stenosis. However, pain is not specific to Crohn's disease, and other etiologies should be considered, particularly gynecologic pathology in an adolescent female. We present an unusual case of endometrial tissue found in the colonic polyp of an adolescent with known Crohn's disease and abdominal pain. Histologic analysis differentiated endometriosis from active inflammation secondary to Crohn's disease. Endometriosis and Crohn's disease are both classified as chronic inflammatory disorders. It remains unclear whether overlapping etiological factors exist for the two disorders. There is a paucity of data on comanagement of endometriosis and inflammatory bowel disease, especially in adolescents. Given the finding of endometriosis in the colonic polyp was unanticipated, this case also reinforces the merits of endoscopic staging of disease whenever significant changes in therapy are considered.

Creutzfeldt-Jakob Disease Mimicking Neurosyphilis: A Complex Presentation, Histopathological Findings, and Special Precautions for Autopsy.

Creutzfeldt-Jakob disease (CJD) is a complex and rapidly fatal prion infection of the central nervous system with characteristic clinical and pathological findings. Herein, we present the case of an 80-year-old man with a 2-month history of rapid cognitive decline and ataxic gait. He was found to have a positive rapid plasma reagin and fluorescent treponemal antibody absorption (FTA-ABS) upon clinical testing and was presumed to have neurosyphilis. His neurological status precipitously declined during his hospitalization and he died. A complete autopsy was performed, which revealed diffuse spongiform change throughout the cerebrum. Brain tissue was sent to the National Prion Disease Surveillance Center, where immunostaining for prion protein (3F4) showed granular deposits, confirming the diagnosis of CJD. There have been rare cases reported in which CJD was clinically suspected but neurosyphilis was confirmed at autopsy. To our knowledge, this is the first case to be published in which the clinical findings strongly favored neurosyphilis, but spongiform encephalopathy was identified at autopsy. We review the clinical, radiographic, electrophysiological, laboratory, and histopathological features of both diseases and discuss the overlapping findings and inherent diagnostic difficulties. We also review the recommended protocols for safely handling suspected prion-infected autopsy tissue. A heightened awareness of the features of CJD and other prion diseases is needed among forensic pathologists, neuropathologists, and general autopsy pathologists to understand how to safely handle the tissue to get definite diagnoses for the decedent's family members and clinical care team.