Human epidermal growth factor receptor 2 (HER2) status in breast cancer: practice points and challenges.

Human epidermal growth factor receptor 2 (HER2)-enriched breast cancer benefits significantly from anti-HER2 targeted therapies. This highlights the critical need for precise HER2 immunohistochemistry (IHC) interpretation serving as a triage tool for selecting patients for anti-HER2 regimens. Recently, the emerging eligibility of patients with HER2-low breast cancers for a novel HER2-targeted antibody-drug conjugate (T-DXd) adds challenges to HER2 IHC scoring interpretation, notably in the 0-1+ range, which shows high interobserver and interlaboratory staining platform variability. In this review, we navigate evolving challenges and suggest practical recommendations for HER2 IHC interpretation.

Intrapancreatic accessory spleen with an epidermoid cyst: a malignant mimicry.

With the liberal use of CT scan for clinical diagnosis, clinicians are faced with an increasing number of pancreatic incidentalomas. Compared with other incidentalomas, pancreatic incidentalomas have higher chances of future malignant transformation. There are many differential diagnoses, and epidermoid cyst in an intrapancreatic accessory spleen (ECIPAS) is extremely rare, with only a handful of reports. Preoperative diagnosis is often complicated, and the final diagnosis is usually only made after surgical resection.We report a 34-year-old man who had an incidentally noted 2.8 cm pancreatic tail cystic lesion on a CT scan done for urinary symptoms. The lesion had a solid nodular component that was worrisome for malignancy, and the patient underwent further evaluation with an MRI scan and endoscopic ultrasound of the pancreas. The differential diagnoses of cystic degeneration of neuroendocrine tumour, branch-duct intraductal papillary mucinous neoplasm with worrisome features or ectopic intrapancreatic spleen were made. A multidisciplinary tumour board recommended surgical resection given risk features of malignancy. The patient subsequently underwent a laparoscopic distal pancreatectomy with splenectomy, and histology confirmed the diagnosis of ECIPAS.Imaging characteristics of ECIPAS are non-specific, and most patients have a diagnosis made only after surgery. Therefore, more evidence is warranted for accurate preoperative imaging diagnosis to avoid unnecessary pancreatic surgery, which is not without its risks.

Nos2-/- mice infected with M. tuberculosis develop neurobehavioral changes and immunopathology mimicking human central nervous system tuberculosis.

BACKGROUND: Understanding the pathophysiology of central nervous system tuberculosis (CNS-TB) is hampered by the lack of a good pre-clinical model that mirrors the human CNS-TB infection. We developed a murine CNS-TB model that demonstrates neurobehavioral changes with similar immunopathology with human CNS-TB. METHODS: We injected two Mycobacterium tuberculosis (M.tb) strains, H37Rv and CDC1551, respectively, into two mouse strains, C3HeB/FeJ and Nos2-/- mice, either into the third ventricle or intravenous. We compared the neurological symptoms, histopathological changes and levels of adhesion molecules, chemokines, and inflammatory cytokines in the brain induced by the infections through different routes in different strains. RESULTS: Intra-cerebroventricular infection of Nos2-/- mice with M.tb led to development of neurological signs and more severe brain granulomas compared to C3HeB/FeJ mice. Compared with CDC1551 M.tb, H37Rv M.tb infection resulted in a higher neurobehavioral score and earlier mortality. Intra-cerebroventricular infection caused necrotic neutrophil-dominated pyogranulomas in the brain relative to intravenous infection which resulted in disseminated granulomas and mycobacteraemia. Histologically, intra-cerebroventricular infection of Nos2-/- mice with M.tb resembled human CNS-TB brain biopsy specimens. H37Rv intra-cerebroventricular infected mice demonstrated higher brain concentrations of inflammatory cytokines, chemokines and adhesion molecule ICAM-1 than H37Rv intravenous-infected mice. CONCLUSIONS: Intra-cerebroventricular infection of Nos2-/- mice with H37Rv creates a murine CNS-TB model that resembled human CNS-TB immunopathology, exhibiting the worst neurobehavioral score with a high and early mortality reflecting disease severity and its associated neurological morbidity. Our murine CNS-TB model serves as a pre-clinical platform to dissect host-pathogen interactions and evaluate therapeutic agents for CNS-TB.

Neurocysticercosis Diagnosed by Taenia solium PCR on Brain Biopsy.

Neurocysticercosis is a common cause for brain lesions and adult-onset epilepsy in endemic countries. However, diagnosis is challenging in the absence of typical radiologic or histopathologic features. In this case report, we present a case of a 35-year-old male with a new-onset seizure and a rim-enhancing temporal lobe lesion. Radiologic features were nonspecific, and brain biopsy was performed. Histologic features showed only nonspecific granulomatous inflammation, and the diagnosis of neurocysticercosis was confirmed only with polymerase chain reaction (PCR) testing on brain biopsy tissue demonstrating PCR products consistent with Taenia solium. This case highlights the diagnostic role of PCR in such clinical situations whereby the diagnosis is unclear after initial routine evaluation.

Intrahepatic splenosis: a world review.

Splenosis is defined as the autotransplantation of viable splenic tissue throughout various anatomic compartments. Intrahepatic splenosis (IHS) is rare and diagnosis is often challenging. This study aims to provide a comprehensive review on IHS. A literature review was performed on PubMed database. Fifty-six articles with 59 reported cases were included. The majority of the patients were male (n = 49, 83.1%). Median age was 51 years. Risk factors for hepatocellular carcinoma (HCC) included hepatitis B (n = 8, 13.6%) and cirrhosis (n = 12, 20.3%). The majority of the patients were asymptomatic (62.7%) and did not have risk factors for HCC (55.9%). We report a diagnostic triad for IHS: 1) previous history of abdominal trauma or splenectomy, 2) absence of risk factors for liver malignancy and 3) typical imaging features. Non-invasive diagnostic tests such as technetium-99m-tagged heat-damaged red blood cell scintigraphy are useful in diagnosis. Malignancy should be ruled out in the presence of risk factors for HCC.

Intraoperative Consultations of Central Nervous System Tumors: A Review for Practicing Pathologists and Testing of an Algorithmic Approach.

Intraoperative consultations or frozen sections for central nervous system (CNS) tumors present a significant challenge for surgical pathologists because of their relative rarity and diversity. Yet, such lesions are encountered by every surgical pathologist, and a basic understanding of clinical, radiological and genetic information is critical to successfully evaluate CNS frozen sections. It is often beneficial to have a systematic approach or an algorithm, and to be aware of the common pitfalls and mimickers when dealing with these lesions. We propose such an algorithm in an effort to construct a sensible approach to CNS frozen sections that considers recent developments in the WHO CNS tumor classification. The algorithm was developed for surgical pathologists who are occasionally faced with making diagnosis of CNS tumors on frozen sections. To test the algorithm and its practicability, we selected a group of tumors among a total of 3288 consecutive intraoperative consultations performed at UCSF between 2013 and 2017. The selected cases represented lesions that may be encountered in everyday surgical pathology and constituted a fair reflection of the main group. The algorithm was used by three of the authors who did not have formal neuropathology training and had been in surgical pathology practice for at least 3 years. There was a very high level of concordance among the authors' diagnosis (interobserver concordance: 0.83-0.97-kappa value) using the algorithm with high intraobserver reliability (concordance 93%, p < 0.001). We suggest that an algorithmic approach is an effective means for the surgical pathologists, and may help reach diagnosis during frozen sections.

Recent Progress in the Pathology and Genetics of Pilocytic and Pilomyxoid Astrocytomas

Pilocytic and pilomyxoid astrocytomas are some of the most common gliomas in children and young adults. These gliomas are indolent neoplasms with long overall survival probability. The genetic characteristics of these neoplasms are well known, and our deepened understanding of their associated molecular alterations has led to the development of novel treatment strategies and approaches. Currently, we can account for some of the unusual behavior, such as oncogene-induced senescence, associated spontaneous regression, anaplastic transformation, and cerebrospinal dissemination, of these gliomas. Nevertheless, enigmatic issues continue to surround these chronic tumors. Here, we review the classical and uncommon clinical pathological and genetic features of these indolent gliomas.

Radiologic Findings in Polyarticular Amyloid Arthropathy and Myopathy in Multiple Myeloma: A Case Report.

BACKGROUND Amyloid arthropathy and myopathy are complications of amyloidosis that can be associated with non-specific imaging findings, which may be challenging to interpret. The report is of a case of polyarticular amyloid arthropathy and myopathy in a 56-year-old man with multiple myeloma and includes a description of the radiographic, computed tomography (CT), and magnetic resonance imaging (MRI) findings. CASE REPORT A 56-year-old man with multiple myeloma presented with chronic polyarticular pain and swelling. Soft tissue thickening of the wrist and knee were found on MRI to be of intermediate T1 weighted imaging (T1WI) and low to intermediate T2 weighted imaging (T2WI) signal intensity. Denervation muscle edema seen in the thenar muscles on the MRI of the right wrist were associated with carpal tunnel syndrome secondary to amyloid deposition. Soft tissue lesions in the periarticular regions of both hip joints were contiguous with subchondral bone lesions. Diffusely scattered myeloma lesions were shown as hyperintense on short tau inversion recovery (STIR) MRI imaging throughout the appendicular and axial skeleton, with vertebral compression fractures. Bilateral iliopsoas involvement with hypertrophy and abnormal surrounding fat reticulated signal intensity was consistent with amyloid myopathy. The patient had a pathological fracture of the right femoral neck and underwent surgical fixation. Histology of the right femoral head confirmed amyloid deposits. CONCLUSIONS Because the clinical presentation and imaging findings of musculoskeletal amyloidosis can be nonspecific, they can result in delay in diagnosis and treatment. Early radiologic identification of polyarticular amyloid arthropathy and myopathy should prompt confirmatory biopsy to confirm the diagnosis.

Disseminated extracranial metastatic meningioma.

Meningiomas are usually low-grade, solitary lesions that rarely metastasize. In this group of central nervous system tumours, the higher grade subtypes are notorious for resistance to conventional chemo-radiation therapies. Recent studies have shown efficacy in the use of bevacizumab in patients with recurrent and, or progressive anaplastic meningioma. The authors report a case of a young patient with recurrent anaplastic meningioma who despite being treated with bevacizumab, progressed with disease dissemination to multiple extracranial sites. Although the majority of meningiomas are amendable to treatment, the higher grade subtypes remain therapeutically challenging. The unexpected resistance to anti-angiogenic therapy in this patient adds another layer of complexity to an elusive subset of a supposedly benign disease. This patient report reflects the need for in-depth studies, molecular characterization and overall, better disease understanding in order to improve prognosis for affected patients.

Necrotizing Fasciitis Caused by Cryptococcus gattii.

Necrotizing fasciitis (NF) is a severe soft-tissue infection that can lead to high morbidity and mortality. The etiology of NF is often polymicrobial. Although rare, fungal organisms have been known to cause NF. Cryptococcus is a fungal infection that may lead to NF. Here we report the case of a 73-year-old man who had diabetes and presented with pain and swelling in the left hand after being bitten by an insect over the dorsum of the hand. Operative débridement revealed NF caused by Cryptococcus gattii. Antifungal medication was started, and the patient underwent multiple débridements of the hand with subsequent skin grafting. Four months later, the hand wound was completely healed. Authors have reported several cases of NF secondary to Cryptococcus neoformans in immunocompromised patients. The emerging C gattii pathogen affects immunocompetent patients. Although the transmission route is mainly respiratory, direct inoculation has been described as well. Ours is the first reported case of NF secondary to C gattii. It is important to consider fungal elements as a source of NF. Appropriate treatment includes aggressive surgical débridement and antifungal therapy.