David W. Ellison, MD, PhD, one of the presenters at the 2016 SNO meeting |
I discuss issues pertaining to the practice of neuropathology -- including nervous system tumors, neuroanatomy, neurodegenerative disease, muscle and nerve disorders, ophthalmologic pathology, neuro trivia, neuropathology gossip, job listings and anything else that might be of interest to a blue-collar neuropathologist.
Thursday, September 29, 2016
Society for Neuro-Oncology meeting to feature several prominent neuropathologists
Tuesday, September 27, 2016
Guest Post: Dr. Nat Pernick, Creator of PathologyOutlines.com
The following is a guest post from Dr. Nat Pernick, creator of PathologyOutlines.com, who reached out to me via Dr. Mark Cohen in search of neuropathology contributors to his website:
PathologyOutlines.com is looking for authors for its
neuropathology chapters, specifically the CNS nontumor
and CNS tumor
chapters. You can also write about Stains and Molecular Markers related to neuropathology. You can either update existing topics or write
about new topics. More information is available on our Instructions for Authors page. The main advantages of being an author are: (a) you are helping the worldwide pathology
community, as we average 15,000 daily visits; (b) it helps your academic career; and (c) and it may improve your writing
skills. We provide an honorarium of $20 per topic, but if money is your
main motivation, this will not be a good fit. You must be a good writer,
and be able to follow our format. You can write about one topic
or many, but they must be approved in advance by us, and we have you do them
one at a time. Senior residents / fellows can write if they are
supervised by a staff pathologist who meets our author requirements. If
interested, email your CV and a list of topics you want to write about (either
update existing topics or write new topics) to Dr. Pernick at NatPernick@gmail.com.
Monday, September 26, 2016
University of Colorado residents show up in force for CAP16
Left to right: Drs. Robinson, Greer, Roberts, Klein, and Graham (with me kneeling) |
Caleb Graham, et al. Pilocytic Astrocytoma: A Diagnostic Consideration in Lateral Ventricular Tumors
Ashley Greer, et al. BRAF Mutational Status in Desmoplastic Infantile Astrocytoma/Ganglioglioma
Colleen Klein, et al. Hemophagocytic Lymphohistiocytosis Discovered Clinically and at Autopsy: A Dual-Institutional, 10-Year Retrospective Review
Sammie Roberts, et al. Double Separate Versus Contiguous Pituitary Adenomas: Magnetic Resonance Imaging Features and Endocrinologic Follow-up
Chase Robinson, et al. Is Testing for IDH1 Mutation in Gliomas by Immunohistochemistry Worthwhile in Persons Older Than 55 Years?
Congratulations, everyone!
Sunday, September 25, 2016
CAP16 Scientific Plenary Session - The Immune Checkpoint Revolution in Cancer Treatment: "Moonshot" or "Pie in the Sky"
I'm attending the scientific plenary session at the 2016 annual meeting of the College of American Pathologists in Las Vegas. The discussion is being led by Dr. Lynette Sholl (pathologist), Dr. Christopher Lathan (medical oncologist), and Barry Nelson (lung cancer patient). Although not directly related to neuropathology, the discussion of the role of biomarkers as a means of directing treatment impacts every area of surgical pathology -- including neuropathology. Mr. Nelson recounted his journey through immunotherapy. Dr. Sholl talked about the paradigm shift that has occurred in cancer therapy by virtue of harnessing T-cell mediated immunity, particularly related to PD-L1. Dr. Lathan, who is Mr. Nelson's physician, talked about his relationship with both the cancer patient and the pathologist. It was pointed out that everything starts with the diagnostic tissue; and the pathologist, as custodian of that tissue, is at the foundation of every patient's battle against cancer. Importantly, Dr. Lathan pointed out that Mr. Nelson is a outlier. Most patients, at this point in our understanding of treatment, do not respond to immunotherapy. Finally, Mr. Nelson pointed out that he does not consider himself cured, but rather "healed". Thanks to immunotherapy, he lives with cancer rather than being cured from it. That relationship with cancer in itself is a paradigm shift, much like the one we have already gotten used to with regard to AIDS.
Left to right: Sholl, Nelson, Lathan
|
Thursday, September 22, 2016
A case of recurrent ligneous conjunctivitis in an adult
Massive fibrin deposition in a case of recurrent ligneous conjunctivitis in an adult |
I recently signed out a case of ligneous conjunctivitis, a rare form of chronic pseudomembranous conjunctivitis that is marked by a massive accumulation of fibrin. The term ligneous (from the Latin term for "woody") refers to the firm consistency of the large masses of fibrin that comprise the pseudomembranes. Ligneous conjunctivitis typically occurs in children but may recur in adults. Treatment is often challenging because the inflammation is persistent and the pseudomembranes often recur rapidly after excision. Histopathology shows two components: granulation tissue and sheets of intensely eosinophilic acellular amorphous material, which has been shown to be composed predominantly of fibrin. The mass of fibrin also incorporates other serum components such as immunoglobulin. Lesions that resemble those found in the conjunctiva can affect other mucous membranes including the larynx, vagina, and ear. Ligneous conjunctivitis is an autosomal recessive trait caused by mutations in the gene for plasminogen on chromosome 6q26.
Reference: Eagle, Ralph C. Eye Pathology: An Atlas and Text [2nd edition] page 55.
Wednesday, September 21, 2016
CAP16 Abstract Highlights - BRAF Mutational Status in Desmoplastic Infantile Astrocytoma/Ganglioglioma
The 2016 annual meeting of the College of American Pathlologists (CAP16) is coming up September 25-28 in Las Vegas. In this series of posts, I'll be featuring poster abstracts of particular interest to neuropathologists.
Ashley Greer and colleagues at the University of Colorado in Poster #194 discuss the BRAF mutational status of DIA/DIG.
Context: Desmoplastic infantile astrocytoma/gangliogliomas (DIA/DIGs) are rare, massively cystic tumors usually found in superficial cerebral hemispheres. They are characterized by prominent desmoplastic stroma, interspersed neoplastic astrocytes, and fewer, if any, neoplastic ganglion cells. While BRAF mutation is found in up to 50% of pediatric gangliogliomas, 2 recent studies found it was rare in DIA/DIGs. We sought to assess BRAF mutation in our DIA/DIGs.
Design: Review of departmental files from 2000–2016 was performed to identify DIA/DIGs, with review of clinical outcome, neuroimaging features, immunohistochemistry (IHC) for astrocytic and neuronal markers, and BRAF VE1. BRAF mutational assessment was undertaken in IHC+/equivocal cases, with additional next generation sequencing whenever possible.
Results: All 6 cases were cerebral-hemispheric, with overlapping neuroimaging features (Figure 76, A and C) and favorable clinical outcomes, although histologic differences were noted. Five of 6 tumors contained a predominantly neoplastic astrocytic population (Figure 76, B), while DIA/DIG from the oldest child (12 months) showed exceptionally large nodules of neoplastic ganglion cells (Figure 76, D). This was the only case to show either BRAF VE1 IHC+ and/or mutation (rare c1799_1800TG.AT; p V600D). Next-generation sequencing on this case, and a comparison astrocytic-dominant DIA/DIG, showed only mutation in BRAF, and not in 26 other commonly mutated genes.
Conclusions: Five of 6 classic DIA/DIGs were negative for BRAF mutation. Previous publications found mutation in 2 of 18 and 1 of 14 cases; 2 of 3 reportedly mutated cases were unusual in that they were in atypical anatomic locations (suprasellar, fourth ventricle), and 1 was in an older child (24-month-old). DIA/DIGs with unusual features may be more likely to show BRAF mutation similar to ganglioglioma.
Ashley Greer and colleagues at the University of Colorado in Poster #194 discuss the BRAF mutational status of DIA/DIG.
Context: Desmoplastic infantile astrocytoma/gangliogliomas (DIA/DIGs) are rare, massively cystic tumors usually found in superficial cerebral hemispheres. They are characterized by prominent desmoplastic stroma, interspersed neoplastic astrocytes, and fewer, if any, neoplastic ganglion cells. While BRAF mutation is found in up to 50% of pediatric gangliogliomas, 2 recent studies found it was rare in DIA/DIGs. We sought to assess BRAF mutation in our DIA/DIGs.
Design: Review of departmental files from 2000–2016 was performed to identify DIA/DIGs, with review of clinical outcome, neuroimaging features, immunohistochemistry (IHC) for astrocytic and neuronal markers, and BRAF VE1. BRAF mutational assessment was undertaken in IHC+/equivocal cases, with additional next generation sequencing whenever possible.
Results: All 6 cases were cerebral-hemispheric, with overlapping neuroimaging features (Figure 76, A and C) and favorable clinical outcomes, although histologic differences were noted. Five of 6 tumors contained a predominantly neoplastic astrocytic population (Figure 76, B), while DIA/DIG from the oldest child (12 months) showed exceptionally large nodules of neoplastic ganglion cells (Figure 76, D). This was the only case to show either BRAF VE1 IHC+ and/or mutation (rare c1799_1800TG.AT; p V600D). Next-generation sequencing on this case, and a comparison astrocytic-dominant DIA/DIG, showed only mutation in BRAF, and not in 26 other commonly mutated genes.
Conclusions: Five of 6 classic DIA/DIGs were negative for BRAF mutation. Previous publications found mutation in 2 of 18 and 1 of 14 cases; 2 of 3 reportedly mutated cases were unusual in that they were in atypical anatomic locations (suprasellar, fourth ventricle), and 1 was in an older child (24-month-old). DIA/DIGs with unusual features may be more likely to show BRAF mutation similar to ganglioglioma.
Tuesday, September 20, 2016
CAP16 Abstract Highlights - Astrocytoma With a Distinct Molecular Signature: MYB Rearrangement and EGFR Amplification
The 2016 annual meeting of the College of American Pathlologists (CAP16) is coming up September 25-28 in Las Vegas. In this series of posts, I'll be featuring poster abstracts of particular interest to neuropathologists.
Doan V. Lai and colleagues at Oklahoma University and St. Jude's in Memphis in Poster #184 describe a combination of low- and high-grade molecular features in a pediatric diffuse astrocytoma.
Diffuse gliomas are uncommon in children but cause significant morbidity and mortality. Unlike diffuse gliomas in adults, pediatric low-grade tumors rarely progress to high-grade disease. Molecular studies are playing an increasingly large role in classifying and predicting therapeutic response in these tumors. MYB rearrangements are common in pediatric diffuse low-grade astrocytomas. EGFR amplification, which occurs in high-grade gliomas, however, is not reported in low-grade gliomas. We report the first case of a pediatric astrocytoma with both MYB rearrangement and EGFR amplification. A 3-year-old boy was found to have a T2 hyperintense, nonenhancing mass in the
left temporal lobe after minor head trauma. Histology showed a diffuse astrocytic tumor with low cell density and bland cytology. Mitotic figures were present, albeit focally, prompting a diagnosis of anaplastic astrocytoma. No necrosis or microvascular proliferation was identified. The Ki-67 labeling index, while generally low, rose to approximately 20%, corresponding to regions of mitotic activity. Interphase fluorescence in situ hybridization analysis showed both rearrangement of MYB in two-thirds of cells and amplification of EGFR in approximately one-quarter of cells. This combination of low- and high-grade molecular features in a pediatric diffuse astrocytoma is so far unique and may
represent the molecular correlate of the rare clinical scenario where a pediatric diffuse astrocytoma, with MYB rearrangement, progresses to high-grade disease.
Doan V. Lai and colleagues at Oklahoma University and St. Jude's in Memphis in Poster #184 describe a combination of low- and high-grade molecular features in a pediatric diffuse astrocytoma.
Diffuse gliomas are uncommon in children but cause significant morbidity and mortality. Unlike diffuse gliomas in adults, pediatric low-grade tumors rarely progress to high-grade disease. Molecular studies are playing an increasingly large role in classifying and predicting therapeutic response in these tumors. MYB rearrangements are common in pediatric diffuse low-grade astrocytomas. EGFR amplification, which occurs in high-grade gliomas, however, is not reported in low-grade gliomas. We report the first case of a pediatric astrocytoma with both MYB rearrangement and EGFR amplification. A 3-year-old boy was found to have a T2 hyperintense, nonenhancing mass in the
left temporal lobe after minor head trauma. Histology showed a diffuse astrocytic tumor with low cell density and bland cytology. Mitotic figures were present, albeit focally, prompting a diagnosis of anaplastic astrocytoma. No necrosis or microvascular proliferation was identified. The Ki-67 labeling index, while generally low, rose to approximately 20%, corresponding to regions of mitotic activity. Interphase fluorescence in situ hybridization analysis showed both rearrangement of MYB in two-thirds of cells and amplification of EGFR in approximately one-quarter of cells. This combination of low- and high-grade molecular features in a pediatric diffuse astrocytoma is so far unique and may
represent the molecular correlate of the rare clinical scenario where a pediatric diffuse astrocytoma, with MYB rearrangement, progresses to high-grade disease.
Saturday, September 17, 2016
CAP16 Abstract Highlights - Naegleria fowleri: Understanding the Clinical Presentation and Autopsy Findings of a Rare and Almost Universally Fatal Central Nervous System Infection
The 2016 annual meeting of the College of American Pathlologists (CAP16) is coming up September 25-28 in Las Vegas. In this series of posts, I'll be featuring poster abstracts of particular interest to neuropathologists.
Alexander T. Damron and colleagues at Baylor College of Medicine in Houston discuss Naegleria fowleri CNS infection in Poster #114:
Naegleria fowleri is a free-living ameba known to cause primary amebic meningoencephalitis (PAM). Moreover, PAM is an acute, fulminating, and hemorrhagic infection that occurs in healthy young children with fresh water exposure in warm climates. It is postulated that Naegleria fowleri enters through the nasal passages and crosses the cribriform plate, where it reaches the subarachnoid space and disseminates into the olfactory lobes. Visvesvara et al (2007) performed a retrospective study of all reported N fowleri infections in the United States from 1937 to 2013 and found 3 survivors in 142 reported cases. Only 27% of the 142 cases were diagnosed before patient death. We present a case of a previously healthy 14-year-old boy who presented with fever, headache, vomiting, and altered mental status 8 days after swimming in a warm freshwater lake. Cerebrospinal fluid studies showed organisms consistent with amoeba (Figure 265, C). Despite neuroprotective measures and antimicrobial medications, the patient was pronounced brain dead 9 days after admission. Autopsy revealed the cause of death to be PAM from infection with N fowleri with cerebral edema and tonsillar herniation (Figure 265, D). Microscopic examination of the central nervous system revealed amoebic organisms infiltrating the meninges and diffusely involving the brain parenchyma in a perivascular distribution (Figure 265, A and B). The most critical aspect in treating patients with PAM is early detection and prompt initiation of multiple antimicrobials and neuroprotective measures.Despite current recommendations, the high mortality rate of these infections (97%–98%) suggests that an effective treatment for PAM is not yet known.
Alexander T. Damron and colleagues at Baylor College of Medicine in Houston discuss Naegleria fowleri CNS infection in Poster #114:
Naegleria fowleri is a free-living ameba known to cause primary amebic meningoencephalitis (PAM). Moreover, PAM is an acute, fulminating, and hemorrhagic infection that occurs in healthy young children with fresh water exposure in warm climates. It is postulated that Naegleria fowleri enters through the nasal passages and crosses the cribriform plate, where it reaches the subarachnoid space and disseminates into the olfactory lobes. Visvesvara et al (2007) performed a retrospective study of all reported N fowleri infections in the United States from 1937 to 2013 and found 3 survivors in 142 reported cases. Only 27% of the 142 cases were diagnosed before patient death. We present a case of a previously healthy 14-year-old boy who presented with fever, headache, vomiting, and altered mental status 8 days after swimming in a warm freshwater lake. Cerebrospinal fluid studies showed organisms consistent with amoeba (Figure 265, C). Despite neuroprotective measures and antimicrobial medications, the patient was pronounced brain dead 9 days after admission. Autopsy revealed the cause of death to be PAM from infection with N fowleri with cerebral edema and tonsillar herniation (Figure 265, D). Microscopic examination of the central nervous system revealed amoebic organisms infiltrating the meninges and diffusely involving the brain parenchyma in a perivascular distribution (Figure 265, A and B). The most critical aspect in treating patients with PAM is early detection and prompt initiation of multiple antimicrobials and neuroprotective measures.Despite current recommendations, the high mortality rate of these infections (97%–98%) suggests that an effective treatment for PAM is not yet known.
Friday, September 16, 2016
CAP16 Abstract Highlights - Heterotopic Cutaneous Meningioma: An Unusual Presentation Occurring in a Patient With a History of Intracranial Meningioma
The 2016 annual meeting of the College of American Pathlologists (CAP16) is coming up September 25-28 in Las Vegas. I'll be attending the meeting this year. In this series of posts, I'll be featuring poster abstracts of particular interest to neuropathologists.
Chibuike L. Enwereuzo and Jean Henneberry at Baystate Medical Center/Tuft University School of Medicine, in Springfield, Massachusetts discuss an unusual case of cutaneous meningioma in a patient with a history of intracranial meningioma (Poster #106):
Meningioma is a neoplasm of the meninges and typically occurs in intracranial sites. Extracranial meningioma has been reported most frequently in the sinonasal tract and skull bone, most often as extension of intracranial meningiomas. Isolated heterotopic meningioma without contiguous intracranial lesion is extremely rare. A 56-year-old woman presented in December 2015 with 2 firm subcutaneous scalp masses: one in the left lateral and the other in the left superior regions. The clinical impression was that of lipoma. Pathologic examination revealed
an ill-defined proliferation of fairly uniform meningothelial cells, infiltrating a fibroblastic stroma with interspersed adipose tissue. The 2 excised lesions had similar histologic features. Immunohistochemical stains were performed, and the tumor cells were positive for epithelial membrane antigen and negative for S100. A diagnosis of atypical meningioma, World Health Organization (WHO) grade II, was made. The patient’s medical history was significant for intracranial meningioma of the frontal lobe in October 2007, which was diagnosed as atypical meningioma, WHO grade II. Comparison of the scalp masses to her prior meningioma revealed a distinctly different morphologic pattern. Considering the 8-year interval between the scalp tumors and intracranial meningioma, it is unlikely that her most recent tumors represent a recurrence or metastasis of the intracranial tumor.
Chibuike L. Enwereuzo and Jean Henneberry at Baystate Medical Center/Tuft University School of Medicine, in Springfield, Massachusetts discuss an unusual case of cutaneous meningioma in a patient with a history of intracranial meningioma (Poster #106):
Meningioma is a neoplasm of the meninges and typically occurs in intracranial sites. Extracranial meningioma has been reported most frequently in the sinonasal tract and skull bone, most often as extension of intracranial meningiomas. Isolated heterotopic meningioma without contiguous intracranial lesion is extremely rare. A 56-year-old woman presented in December 2015 with 2 firm subcutaneous scalp masses: one in the left lateral and the other in the left superior regions. The clinical impression was that of lipoma. Pathologic examination revealed
an ill-defined proliferation of fairly uniform meningothelial cells, infiltrating a fibroblastic stroma with interspersed adipose tissue. The 2 excised lesions had similar histologic features. Immunohistochemical stains were performed, and the tumor cells were positive for epithelial membrane antigen and negative for S100. A diagnosis of atypical meningioma, World Health Organization (WHO) grade II, was made. The patient’s medical history was significant for intracranial meningioma of the frontal lobe in October 2007, which was diagnosed as atypical meningioma, WHO grade II. Comparison of the scalp masses to her prior meningioma revealed a distinctly different morphologic pattern. Considering the 8-year interval between the scalp tumors and intracranial meningioma, it is unlikely that her most recent tumors represent a recurrence or metastasis of the intracranial tumor.
Thursday, September 15, 2016
CAP16 Abstract Highlights - Extraventricular Neurocytoma: A Diagnostic Pitfall Mimicking Oligodendroglioma
The 2016 annual meeting of the College of American Pathlologists (CAP16) is coming up September 25-28 in Las Vegas. I'll be attending the meeting this year. In this series of posts, I'll be featuring poster abstracts of particular interest to neuropathologists.
Xinhai Zhang and colleagues at Loma Linda University in California discuss in Poster #198 discuss the problem of distinguishing extraventricular neurocytoma from oligodendroglioma:
Context: Extraventricular neurocytoma (EVN) mimics oligodendroglioma in terms of location and morphology. Oligodendrogliomas usually progress, while EVNs, other than atypical EVNs, typically do
not.
Design: We retrospectively analyzed studies encompassing 155 EVN cases published since 2000 for distinguishing features.
Results: Summarized differentiating features include the fact that EVNs have a peak incidence in the third and fourth decade of life, whereas the peak incidence of oligodendrogliomas is from the fourth to sixth decade. EVNs can have small areas of nucleus-free neuropil as well as thickened hyalinized blood vessels, features not seen in oligodendrogliomas. Immunohistochemically, oligodendrocyte lineage transcription factor 2 (OLIG2) is immunopositive in oligodendroglioma but negative in EVNs. In addition, EVNs are consistently positive for synaptophysin but rarely positive for GFAP, whereas oligodendrogliomas are variably positive for synaptophysin and more often positive for GFAP. Many oligodendrogliomas show loss of heterozygosity on
chromosomes 1p and 19q. These changes are not seen in EVNs except for atypical EVN with MIB-1 proliferation indices greater than 3%. IDH1/2 mutations are present in many oligodendrogliomas but not EVNs. Ultrastructurally, EVN tumor cells demonstrate numerous neuritelike cell processes as well as cell bodies with dense-core neurosecretory granules, whereas oligodendroglioma cells show plump and rounded cytoplasm without forming cellular processes, synaptic structures, or dense-core granules. Rare hypothalamic neurocytomas express TTF1 and vasopressin.
Conclusions: While clinicopathologic features are diagnostically helpful, additional molecular analyses are needed to better characterize the spectrum of EVNs and their distinction from oligodendrogliomas.
Xinhai Zhang and colleagues at Loma Linda University in California discuss in Poster #198 discuss the problem of distinguishing extraventricular neurocytoma from oligodendroglioma:
Context: Extraventricular neurocytoma (EVN) mimics oligodendroglioma in terms of location and morphology. Oligodendrogliomas usually progress, while EVNs, other than atypical EVNs, typically do
not.
Design: We retrospectively analyzed studies encompassing 155 EVN cases published since 2000 for distinguishing features.
Results: Summarized differentiating features include the fact that EVNs have a peak incidence in the third and fourth decade of life, whereas the peak incidence of oligodendrogliomas is from the fourth to sixth decade. EVNs can have small areas of nucleus-free neuropil as well as thickened hyalinized blood vessels, features not seen in oligodendrogliomas. Immunohistochemically, oligodendrocyte lineage transcription factor 2 (OLIG2) is immunopositive in oligodendroglioma but negative in EVNs. In addition, EVNs are consistently positive for synaptophysin but rarely positive for GFAP, whereas oligodendrogliomas are variably positive for synaptophysin and more often positive for GFAP. Many oligodendrogliomas show loss of heterozygosity on
chromosomes 1p and 19q. These changes are not seen in EVNs except for atypical EVN with MIB-1 proliferation indices greater than 3%. IDH1/2 mutations are present in many oligodendrogliomas but not EVNs. Ultrastructurally, EVN tumor cells demonstrate numerous neuritelike cell processes as well as cell bodies with dense-core neurosecretory granules, whereas oligodendroglioma cells show plump and rounded cytoplasm without forming cellular processes, synaptic structures, or dense-core granules. Rare hypothalamic neurocytomas express TTF1 and vasopressin.
Conclusions: While clinicopathologic features are diagnostically helpful, additional molecular analyses are needed to better characterize the spectrum of EVNs and their distinction from oligodendrogliomas.
Wednesday, September 14, 2016
CAP16 Abstract Highlights: Accuracy of Central Nervous System Intraoperative Consultation Among Neuropathologists and General Pathologists
The 2016 annual meeting of the College of American Pathlologists (CAP16) is coming up September 25-28 in Las Vegas. I'll be attending the meeting this year. In this series of posts, I'll be featuring poster abstracts of particular interest to neuropathologists.
Timothy Harcom and Patrick Malafronte of the Walter Reed National Military Medical Center address in Poster #202 the accuracy of CNS intraoperative consultation:
Context: The reported accuracy of central nervous system (CNS) intraoperative consultation approaches 90%. Many of these studies, however, only include analysis by neuropathologists. The accuracy of diagnoses among general pathologist has not been extensively studied.
Design: All CNS intraoperative consultations during a consecutive 5-year period were evaluated. The consultations were separated into 2 groups: those consultations evaluated by a neuropathologist and those evaluated by a general pathologist. Four categories of frozen-permanent concordance were created: complete concordance, partial concordance, discordance, and deferral of diagnosis beyond the appraisal of adequate diagnostic tissue.
Results: A total of 170 CNS intraoperative consultations were identified: 91 cases with neuropathology evaluation and 79 cases with general pathologist evaluation only. The results (numbers of cases) were as follows, respectively: total concordance of 43 and 25; partial concordance of 39 and 31; discordance of 5 and 6; deferral of diagnosis of 4 and 17. Two of these comparisons produced statistically significant results (P< .05), complete concordance, showing a 72% increase, and deferral of diagnosis, showing a 76% decrease when the cases were evaluated by a neuropathologist.
Conclusions: The increased reliance on deferral of diagnosis and a reduced concordance rate among general pathologists points to a potential learning deficit that could be overcome through targeted education programs, similar to the ThinPrep Pap Proficiency Test, with the aim of increasing the quality of information provided during CNS intraoperative consultation.
Timothy Harcom and Patrick Malafronte of the Walter Reed National Military Medical Center address in Poster #202 the accuracy of CNS intraoperative consultation:
Context: The reported accuracy of central nervous system (CNS) intraoperative consultation approaches 90%. Many of these studies, however, only include analysis by neuropathologists. The accuracy of diagnoses among general pathologist has not been extensively studied.
Design: All CNS intraoperative consultations during a consecutive 5-year period were evaluated. The consultations were separated into 2 groups: those consultations evaluated by a neuropathologist and those evaluated by a general pathologist. Four categories of frozen-permanent concordance were created: complete concordance, partial concordance, discordance, and deferral of diagnosis beyond the appraisal of adequate diagnostic tissue.
Results: A total of 170 CNS intraoperative consultations were identified: 91 cases with neuropathology evaluation and 79 cases with general pathologist evaluation only. The results (numbers of cases) were as follows, respectively: total concordance of 43 and 25; partial concordance of 39 and 31; discordance of 5 and 6; deferral of diagnosis of 4 and 17. Two of these comparisons produced statistically significant results (P< .05), complete concordance, showing a 72% increase, and deferral of diagnosis, showing a 76% decrease when the cases were evaluated by a neuropathologist.
Conclusions: The increased reliance on deferral of diagnosis and a reduced concordance rate among general pathologists points to a potential learning deficit that could be overcome through targeted education programs, similar to the ThinPrep Pap Proficiency Test, with the aim of increasing the quality of information provided during CNS intraoperative consultation.
Tuesday, September 13, 2016
CAP16 Abstract Highlights -- Pilocytic Astrocytoma: A Diagnostic Consideration in Lateral Ventricular Tumors
The 2016 annual meeting of the College of American Pathlologists (CAP16) is coming up September 25-28 in Las Vegas. I'll be attending the meeting this year. In this series of posts, I'll be featuring poster abstracts of particular interest to neuropathologists.
Caleb Graham and colleagues at the University of Colorado (Poster #193) discuss the differential diagnosis of oligodendroglioma mimickers in the lateral ventricles. Here's the updated abstract:
Context: The most common lateral ventricular tumors are choroid plexus papilloma and meningioma, with a fewer number of cases of subependymoma, subependymal giant cell astrocytoma, lymphoma, and metastasis. Lateral ventricular pilocytic astrocytomas (PAs) are uncommon, seldom reported as a series, and must be excluded from neurocytoma and glioneuronal tumors.
Design: Our brain tumor databases were reviewed to identify all lateral ventricular PAs seen from 2000 to 2016. Magnetic resonance imaging studies were reviewed to exclude cases that were primarily parenchymal with secondary protrusion into the lateral ventricles. Immunohistochemical workup for glial and neuronal markers, as well as BRAF VE1 (surrogate marker for BRAF V600E mutation), were undertaken. KIAA:BRAF fusion status and electron microscopy were performed in 2 cases.
Results: Four cases (ages 13, 21, 28, and 43 years) were identified. By neuroimaging 2 cases displaced the septum (Figure 75, A) and 1 was near the trigone (Figure 75, B). These cases had generated wide radiologic differential diagnoses, especially central neurocytoma in the 2 cases displacing the septum. Histologically, 3 of the 4 were predominantly composed of small round cells with perinuclear halos (Figure 75,C) and showed few piloid areas or Rosenthal fibers. These cases also showed patchy synaptophysin immunohistochemical positivity, traditionally associated with neuronal tumors (Figure 75, D), but those evaluated by electron microscopy failed to show neuronal lineage.Unlike typical gangliogliomas, all 4 were BRAF VE1 negative.
Conclusions: Lateral ventricle PAs are uncommon but should be considered when encountering lateral ventricular tumors.
Caleb Graham and colleagues at the University of Colorado (Poster #193) discuss the differential diagnosis of oligodendroglioma mimickers in the lateral ventricles. Here's the updated abstract:
Context: The most common lateral ventricular tumors are choroid plexus papilloma and meningioma, with a fewer number of cases of subependymoma, subependymal giant cell astrocytoma, lymphoma, and metastasis. Lateral ventricular pilocytic astrocytomas (PAs) are uncommon, seldom reported as a series, and must be excluded from neurocytoma and glioneuronal tumors.
Design: Our brain tumor databases were reviewed to identify all lateral ventricular PAs seen from 2000 to 2016. Magnetic resonance imaging studies were reviewed to exclude cases that were primarily parenchymal with secondary protrusion into the lateral ventricles. Immunohistochemical workup for glial and neuronal markers, as well as BRAF VE1 (surrogate marker for BRAF V600E mutation), were undertaken. KIAA:BRAF fusion status and electron microscopy were performed in 2 cases.
Results: Four cases (ages 13, 21, 28, and 43 years) were identified. By neuroimaging 2 cases displaced the septum (Figure 75, A) and 1 was near the trigone (Figure 75, B). These cases had generated wide radiologic differential diagnoses, especially central neurocytoma in the 2 cases displacing the septum. Histologically, 3 of the 4 were predominantly composed of small round cells with perinuclear halos (Figure 75,C) and showed few piloid areas or Rosenthal fibers. These cases also showed patchy synaptophysin immunohistochemical positivity, traditionally associated with neuronal tumors (Figure 75, D), but those evaluated by electron microscopy failed to show neuronal lineage.Unlike typical gangliogliomas, all 4 were BRAF VE1 negative.
Conclusions: Lateral ventricle PAs are uncommon but should be considered when encountering lateral ventricular tumors.
Monday, September 12, 2016
CAP16 Abstract Highlights: Predictive Markers for Meningioma Grading
The 2016 annual meeting of the College of American Pathlologists (CAP16) is coming up September 25-28 in Las Vegas. I'll be attending the meeting this year. In this series of posts, I'll be featuring poster abstracts of particular interest to neuropathologists.
Hussam Abu-Farakh and colleagues from Ibn Haytham Hospital in Amman, Jordan present a poster (#178) on predictive markers for meningioma grading. Here is an excerpt from the abstract:
Design: We studied 244 meningioma cases during the last 10 years at our center. All cases were studied for the following: sex, tumor size, mitotic count, the presence of small cell component (SCC), brain invasion (BRI), bone invasion (BNI), necrosis, and atypia (defined as pleomorphism, prominent nucleoli 6 large hyperchromatic nuclei). Additionally, immunohistochemistry for the percentage of progesterone receptor (PRG) expression, p53, and Ki-67 was calculated.
Results: Grade I and II meningiomas were more common in females, but grade III tumors were equally distributed (P , .05)
The poster also breaks down specific percentages for different histologic features of each of the grades in their series. For example, with regard to progesterone receptor (PR) immunohistochemical expression, 65% are positive in Grade I meningiomas, 32% are positive in grade II, and only 3% are positive in grade III.
Hussam Abu-Farakh and colleagues from Ibn Haytham Hospital in Amman, Jordan present a poster (#178) on predictive markers for meningioma grading. Here is an excerpt from the abstract:
Design: We studied 244 meningioma cases during the last 10 years at our center. All cases were studied for the following: sex, tumor size, mitotic count, the presence of small cell component (SCC), brain invasion (BRI), bone invasion (BNI), necrosis, and atypia (defined as pleomorphism, prominent nucleoli 6 large hyperchromatic nuclei). Additionally, immunohistochemistry for the percentage of progesterone receptor (PRG) expression, p53, and Ki-67 was calculated.
Results: Grade I and II meningiomas were more common in females, but grade III tumors were equally distributed (P , .05)
The poster also breaks down specific percentages for different histologic features of each of the grades in their series. For example, with regard to progesterone receptor (PR) immunohistochemical expression, 65% are positive in Grade I meningiomas, 32% are positive in grade II, and only 3% are positive in grade III.
Tuesday, September 6, 2016
Featured Neuropathologist: Karra A. Jones, MD, PhD
Karra Jones, MD, PhD |
Karra Jones grew up in
Kansas City where she completed her M.D. and Ph.D. at the University of Kansas
School of Medicine. Karra’s graduate work focused on the evaluation of muscle
spindle innervation by large peripheral nerve fibers and proprioceptive abnormalities
in diabetes. During her time at KUMC, Karra was inspired by the strong history
of neuropathology in Kansas City started by the dearly missed John Kepes and
continued by her amazing mentor Kathy Newell. Karra traveled to the West Coast
in 2010 to train in combined anatomic pathology/neuropathology under Lawrence
Hansen, Scott VandenBerg, Subhojit Roy, and Henry Powell at the University of
California, San Diego. There she focused on brain tumor research with Scott
VandenBerg and Steve Gonias and developed a clinical interest in neuromuscular
pathology. She was fortunate to obtain additional training in muscle pathology at
UCSD with Diane Shelton in The Comparative Neuromuscular Laboratory. Karra
joined the staff at UCSD in 2014 where she headed the neuromuscular service,
participated in the general neurosurgical service, collaborated with molecular
pathology on brain tumor molecular testing protocols/testing, supervised a
biomarker laboratory, and was a co-director of the tissue biorepository. Karra very
recently returned to the Midwest to join the highly talented neuropathology
group at the University of Iowa where she is very excited to be practicing
alongside Steve Moore, Leslie Bruch, Pat Kirby, and Gary Baumbach.
1. Why did you decide to become a neuropathologist?
I became interested in the neurosciences after spending a year as a research assistant at Emory University in the Department of Neurology prior to medical school. Then, during graduate school at KUMC, my interest in tissue morphology was peaked after spending hours each day under a confocal microscope staring at muscle spindle innervation (what a gorgeous thing!) While at KUMC, I was extremely lucky to have Kathy Newell take me on as a mentee, and after that I was hooked. Almost everyone in my family is an artist, and I often felt like the outsider in that regard. But I realized with pathology, and in particular the beauty of neuropathology, I was a different kind of artist in my own right. Examining, classifying, and photographing brain tumors, neuromuscular diseases, and neurodegenerative diseases seemed like the most fun I could ever have at work. And I continue to have fun every day as a neuropathologist.
I became interested in the neurosciences after spending a year as a research assistant at Emory University in the Department of Neurology prior to medical school. Then, during graduate school at KUMC, my interest in tissue morphology was peaked after spending hours each day under a confocal microscope staring at muscle spindle innervation (what a gorgeous thing!) While at KUMC, I was extremely lucky to have Kathy Newell take me on as a mentee, and after that I was hooked. Almost everyone in my family is an artist, and I often felt like the outsider in that regard. But I realized with pathology, and in particular the beauty of neuropathology, I was a different kind of artist in my own right. Examining, classifying, and photographing brain tumors, neuromuscular diseases, and neurodegenerative diseases seemed like the most fun I could ever have at work. And I continue to have fun every day as a neuropathologist.
2. Name a couple of important professional mentors. Why were they important to you?
I already mentioned Kathy Newell – Kathy has been an amazing mentor throughout my training and early career even though I haven’t worked with her directly since medical school. She first inspired me to pursue neuropathology with her amazing eye, calm demeanor, and kind heart. She also taught me about the importance of a “Neuropathology Family” introducing me to John Kepes and encouraging me to work with B.K. DeMasters during my last year of medical school, which helped solidify my decision to pursue combined AP/NP training. Another very important mentor is Lawrence Hansen (although he would argue that mentor means “cross-dresser” as the word is derived from Homer’s Odyssey in which Athena assumes the form of Mentor.) Larry is one of the most talented teachers and morphologists I have ever had the opportunity to work with. His “Hansen-isms” are embedded in my brain for life and as a neuropathologist and educator I will forever pass them on to my fellows, residents, students and mentees. Not only is Larry an amazing teacher and mentor, but also he is a very good friend and human being. I was also extremely lucky to be mentored by Scott VandenBerg on brain tumor diagnosis, molecular testing, and basic science research. Without Scott’s influence, I wouldn’t be where I am today.
3. What advice would you give to a pathology resident interested in doing a neuropathology fellowship?
Do it! Neuropathology is clearly the best of all pathology specialties. But in all seriousness, Neuropathology training will give you a highly desirable skill set that will prepare you for a large variety of career paths. There are many ways to “differentiate” as a neuropathologist – academic, private practice, research, clinical, tumors, neuromuscular, neurodegenerative, etc. So, prior to your NP training, try to think about what you would like to do as a career after it’s all said and done, but remember to always be flexible and allow yourself to change your mind (it happens in medicine quite often). Neuropathology can also be a good specialty to combine with others such as pediatric pathology and forensic pathology, making you a highly desirable job candidate for varied positions. Don’t be intimidated by the 2 year commitment of the NP fellowship. One extra year in training is nothing in the grand scheme of life and only prepares you even better for the day you click “finalize” on your first case (or it gives you more time to work toward getting grant funding before the clock starts ticking). Right now, there are many job openings in neuropathology – we need bright, motivated, and enthusiastic trainees to become the next generation of neuropathologists.
4. What city would you like a future American Association of Neuropathologists meeting to be held and why?
I would love for the meeting to be held in San Francisco again. I love visiting the city and always look for excuses to return.
Subscribe to:
Posts (Atom)
Neuropathology Blog is Signing Off
Neuropathology Blog has run its course. It's been a fantastic experience authoring this blog over many years. The blog has been a source...
-
Shannon Curran, MS with her dissection Shannon Curran, a graduate student in the Modern Human Anatomy Program at the University of Co...
-
Last summer I put up a post about a remarkable whole nervous system dissection that was carried out at the University of Colorado School of ...