After completion of all macroscopic and microscopic investigations, one must synthesize the data with the other information already gathered (clinical history, radiographic, microbiologic, genetic, or other ancillary data) to formulate a coherent final interpretation which best fits all the findings. Rarely will any finding stand alone or trump all others.
Real-time correspondence with the prosector of the general autopsy, and/or placental pathologist, is highly recommended in integrating all findings, before report finalization. In particular, if the neuropathological findings are unexpected or primary to understanding the demise, the autopsy prosector must be notified in advance of receiving a completed report, as a matter of “best practice” as well as professional courtesy. Usually, their impressions of the case are valuable as confirmation that the neuropathology is consistent and reasonable.
When the preponderance of data clearly supports a singular interpretation, there is a corresponding level of certainty in the wording of the diagnoses. This certainty presumes that all desired elements of the history and ancillary studies are available. In circumstances in which data points are missing, the level of certainty to be conveyed in the final diagnosis may need to be lowered, usually by the use of terms or phrases such as “suggestive of,” “consistent with,” or “with elements of” in the line diagnoses. With even less certainty, a line diagnosis may not be justified, instead utilizing descriptive terms, followed by a separate comment indicating the reason for reluctance in offering diagnostic certainty. In general, it is always worthwhile to spell out the thought process undertaken, so that later readers (who may be in possession of additional information or perspective) appreciate the rationale used in the final formulation. Speculation should be done sparingly in a written report and clearly labeled as such.
When a finding is of uncertain significance, that should be stated. An example of this is the presence of reactive-appearing astrocytes in the cerebral white matter in stillbirths or infant deaths, which, while hard to defend as “normal,” may or may not in and of itself reflect a significant pathologic state. Assignment of significance to a given finding also depends heavily on “the company it keeps.” Thus, to continue with the example of white matter gliosis, one may have greater concern if, in addition to the presence of reactive astrocytes, one also sees white matter mineralization and neuronal loss and gliosis of deep gray structures, generating a picture more consistent with hypoxia-ischemia.
Consultation is never a bad idea. Even if this takes the form of merely running a case by a colleague down the hall, another pair of eyes on the case (or at least on the report) can serve to bring overlooked questions, alternative interpretations, or ambiguous communication to the fore. If an expert is formally consulted, it is best to furnish him or her with as much data as is practical: imaging (prenatal, postnatal, postmortem), maternal/pregnancy history, general autopsy findings, and so on, as well as any concern you may have that the case may be (or become) of medicolegal dispute. Including their opinion in the original report or as an Addendum is usually advisable. Keep in mind that the “best” experts themselves consult others – it is not a sign of insecurity but rather of recognition of the difficulty these cases can present!
Of course, the term “consultation” also refers to the exploration of the medical literature, including textbooks (edited or written by acknowledged experts in the field), primary articles, and databases, many of which are now available online (see Table 16.1) [1–3]. Faced with what may be an initially unfamiliar array of findings, one finds these databases to be extremely useful not only in assisting in the recognition of phenotypic entities and syndromes (and thus more accurate diagnosis) but also in directing next steps in genetic analyses for patient families.
| Resource | Use | Web page |
|---|---|---|
| FindZebra | Free text search with automatic symptom extraction and inference using Bayesian networks; faceted search | www.findzebra.com |
| London Dysmorphology Database | Database on rare dysmorphic syndromes | https://www.face2gene.com/lmd-library-london-medical-database-dysmorphology/ |
| OMIM | Free text search | www.omim.org |
| Phenomizer | Patient features and symptoms are input using HPO (Human Phenotype Ontology) questionnaire; uses custom inference specialized for ontologies | compbio.charite.de/phenomizer |
| POSSUM | Dysmorphology database of multiple malformations, metabolic, teratogenic, chromosomal, and skeletal syndromes and their images | www.possum.net.au |
| PubMed | Free text search | www.ncbi.nlm.nih.gov/pubmed |
| SimulConsult | Uses Bayesian inference to compile differential diagnosis | www.simulconsult.com/ |
| Watson | Custom inferential system based on various statistical methods | Not publicly accessible |
| WebMD | Uses either free text search or knowledge-based symptom questionnaire system | www.webmd.com |
In reporting, the examinations undertaken and the corresponding findings should be documented in a logical fashion. Templates may be useful for consistency, and as a reminder of what data (including “negative” findings) to specifically mention (see Chapter 17). The macroscopic and microscopic descriptions should be just that: descriptions, not overt diagnoses. This leaves open the possibility for alternative interpretations, which may come up at later stages in the examination, during the “synthesis” phase, or after consultation.
References
Introduction
The conventional fetal and infant autopsy remains the gold standard for determining the cause of death and the final summary of all pathologic findings, even in the era of new emerging technologies. Therefore, timeliness, accuracy, and completeness continue to be key quality parameters in neuropathology, along with clarity in communication and conformance to current standards [1, 2]. To improve the quality and uniformity of autopsy reports, pathology organizations have developed several guidelines defining key parameters for macroscopic and histopathology autopsy reporting. One example is the Autopsy Lexicon, prepared in 2000 by the Autopsy Committee of the College of American Pathologists with the intention to foster more uniform reporting of autopsy information, which may facilitate review of autopsy reports and retrieval of information from electronically stored autopsy reports [3].
Given the consensus among the neuropathologists that checklists and/or structured templates improve consistency, turnaround time, and workflow, in this chapter we provide examples of presenting key parameters in pediatric autopsy reports, based on the following outline:
I. Diagnoses
II. Gross and microscopic description
III. Clinical summary
IV. Comment
V. References
A Perinatal Neuropathology Report (Example)
| FINAL NEUROPATHOLOGIC DIAGNOSIS: |
| NEUROPATHOLOGY GROSS DESCRIPTION: |
| Brain cutting was performed on ___. The entire, unfixed brain weighs ___. The brain fixed in PFA/formalin is examined. The postmortem interval was ___ hours. The dura mater ___. The leptomeninges are ___. The cerebrum is ___. Gyral and sulcal development shows ___ which is appropriate for age. There is ___ edema. There is ___ evidence of transtentorial herniation. The cerebrum _ proportional to the size of the cerebellum. The Circle of Willis is ___. The vertebral and basilar arteries are ___. The cranial nerves are all present and ___ abnormalities. Externally the cerebellum and brainstem are well-formed and with/without focal abnormalities. |
| The brainstem with the cerebellum is separated from the cerebrum at the rostral midbrain level, and the cerebrum is cut into approximately 1 cm. intervals in the coronal plane. The cerebral cortex ___ well-formed: the cortical ribbon is of ___ thickness and there are ___ focal lesions. The ratio of cortical gray-to-white matter volume is ___. There ___ focal lesions within the central white matter, including hemorrhages, infarcts, or abscess formation. ___ areas of focal necrosis or cystic cavities in the periventricular white matter (periventricular leukomalacia) are detected. Myelin is detected grossly in ___. |
| The ventricles are ___. Germinal matrix cysts ___ present. There ___ intraventricular or intraplexal hemorrhage. |
| The thalamus, hypothalamus, caudate, putamen, globus pallidus, amygdala, and hippocampus are ___ and ___ focal lesions. |
| The pineal gland ___ identified. It measures _ x _ x _ cm. There ___ appreciable abnormalities. |
| The cerebellum is separated from the brainstem and cut in the parasagittal plane. Externally the cerebellar vermis and hemispheres are ___. The folia are ___ distinct and ___ atrophy. The white matter in the vermis and lateral hemispheres is ___. Myelin is detected grossly in ___. The dentate nucleus is ___ well-formed and ___ focal lesions. |
| The brainstem is sectioned in the transverse plane. It is ___ well-formed. The aqueduct of Sylvius is ___ patent. The tegmentum at all levels appears of ___ size and there ___ focal lesions. The basis pontis appears of ___ size. The principal inferior olives are ___ convoluted. Myelin is ___ detected grossly in the [superior, middle, and inferior cerebellar peduncles, medial lemniscus, lateral lemniscus, decussation of the superior cerebellar peduncle, hilum and amiculum of the inferior olive, medial longitudinal fasciculus, and ___.] |
| The spinal cord is ___ well-formed externally. The dura is ___. The leptomeninges are ___. The spinal cord is cut in the transverse plane at approximately 1 cm. intervals. Myelin is ___ detected grossly in the ___. There are ___ focal lesions. |
| NEUROPATHOLOGY MICROSCOPIC DESCRIPTION: |
| STAINS: ___ slides with sections stained with hematoxylin and eosin/Luxol fast blue (H&E/LFB) are examined microscopically. In addition, selected slides are immunostained for ___. The following histochemical stains are applied to selected slides: ___. |
| MENINGES: There ___ acute or chronic inflammation, or ___ hemorrhage. The blood vessels are ___ inflammation or thromboemboli. The dura shows ___ evidence of recent or remote hemorrhage. Inflammation is ___ present. There is ___ extramedullary hematopoiesis. |
| CEREBRAL CORTEX: Representative sections are examined from ___ lobes. The cerebral cortex shows ___ lamination and differentiation of neuronal subtypes. There is ___ cytoplasmic shrinking of neurons and pericellular vacuolation throughout the cerebral cortex in all laminae. ___ vacuolation of the neuropil is ___ present. Scattered neurons ___ eosinophilic cytoplasm. Laminar necrosis is ___ present. There ___ apparent neuronal loss or gliosis. There ___ abnormal neuronal storage. Viral inclusions, perivascular inflammation, or glial nodules are ___ identified. The parenchymal blood vessels are ___ congested. |
| CEREBRAL WHITE MATTER: Representative sections are examined from ___ lobes. There ___ focal lesions within the periventricular, deep, or intragyral white matter. Infarcts, focal necrosis, cystic cavities, hemorrhages, or abscesses are ___ identified. In the ___, there is a focal lesion characterized by coagulative necrosis with intense eosinophilia and pyknosis of glial nuclei, reactive astrocytes, reactive (rod-shaped) microglia, axonal spheroids, and ferruginized axonal processes. There ___ reactive gliosis throughout the white matter in all regions, including the corpus callosum, optic radiation, anterior commissure, and ___. The reactive astrocytes are ___ characterized by abundant, hypertrophic, eosinophilic cytoplasm and enlarged nuclei; their cytoplasm stains positively for GFAP. The oligodendrocytes ___ appear to be decreased in number. Acutely damaged glia, with pyknotic nuclei, are ___ present. Globules are ___ identified. The parenchymal blood vessels are ___ congested. |
| The degree of myelination is visually assessed with a grading scale of 0–4 in which an internal standard of degree 3 (“mature myelin”) is used (inferior cerebellar peduncle) (Brody et al., J Neuropathol Exp Neurol. 1987;46:283–301; Kinney et al., J Neuropathol Exp Neurol 1988; 47:217–234). The degree of myelination is given for the following selected white matter sites: frontal pole, ___; occipital pole, ___; posterior frontal white matter, ___; parietal white matter (level of atrium), ___; temporal lobe white matter (level of the lateral geniculate body), ___; temporal pole, ___; corona radiata, ___; posterior limb, ___; anterior limb, ___; corpus callosum (body), ___; corpus callosum (rostrum), ___; corpus callosum (splenium), ___; anterior commissure, ___; external capsule, ___; extreme capsule, ___; putamenal pencils, ___; fornix, ___; alveus, ___; fimbria, ___; cingulum, ___; stria medullaris thalami, ___; ansa lenticularis, ___; distal optic radiation, ___; proximal optic radiation, ___; optic tract, ___. |
| VENTRICULAR LINING AND CHOROID PLEXUS: The ependyma appears ___. There is ___ evidence of recent or remote hemorrhage or inflammation in the subependymal regions, including in the site of the ganglionic eminence. Germinal matrix cysts are ___ identified. The glomus of the choroid plexus appears ___. There ___ a hemorrhage within the glomus of the choroid plexus. There ___ intraventricular hemorrhage. |
| THALAMUS: This structure ___ well-formed, with ___ differentiation of neuronal subtypes. There ___ apparent neuronal loss or gliosis. Focal lesions ___ present. |
| HYPOTHALAMUS: This structure is ___ well-formed. There ___ focal lesions. |
| BASAL GANGLIA: The shape and relationship of caudate, putamen, and globus pallidus appear ___. There ___ appreciable neuronal loss and/or gliosis. Focal lesions ___ present. |
| AMYGDALA: This structure is ___ well-formed. There ___ apparent neuronal loss or gliosis. Focal lesions are ___ present. |
| BASAL FOREBRAIN: The substantia innominata is ___ well-formed. There are ___ focal lesions. |
| HIPPOCAMPUS AND SUBICULUM: This structure is ___ well-formed. There ___ neuronal shrinking in the pyramidal cell layer, particularly CA1. The dentate gyrus is ___. In the subiculum, there ___ gliosis, associated with neuronal shrinking and ___ neuronal loss. Acute neuronal necrosis is ___ present in CA1, CA2, CA3, and CA4 of Ammon’s horn, dentate gyrus, and subiculum. The entorhinal cortex is ___ well-formed; there are ___ focal lesions. |
| CEREBELLUM: Representative sections of the vermis and lateral cerebellum are examined. The cerebellar cortex is ___ well-formed. The external granule cell layer is approximately ___ cells thick. The Purkinje cells are ___ appropriately differentiated. The internal granule cell layer is ___ well-formed. The molecular layer ___ appear thinned. There ___ apparent neuronal loss in the Purkinje cell and internal granular layers. The Purkinje cells appear ___ in all regions; there is ___ loss. Their cytoplasm is ___ eosinophilic. Bergmann gliosis ___ present. The granule cells in the internal granule cell layer appear ___ throughout all regions. There ___ focal scars within the cortex. There ___ reactive gliosis throughout the white matter. There is ___ in oligodendrocyte number. There are ___ scattered heterotopias, composed of ___, in the white matter of the vermis and lateral hemisphere; these are not uncommon incidental findings in perinatal and infant brains. The dentate nucleus is ___ well-formed: hypertrophic astrocytes are present to a ___ degree, but there is ___ obvious neuronal loss. Focal neuronal loss is ___ identified within the dentate nucleus. There is ___ parenchymal congestion. The degree of myelination is assessed in the following white matter sites: vermis, ___; central white matter of the lateral cerebellum, ___; dentate hilum, ___; peridentate capsule, ___. |
| BRAINSTEM: Representative sections are examined in the midbrain, pons, and medulla levels. The nuclei are ___ in their proper positions, with ___ differentiation of neuronal subtypes. The fiber tracts are ___ in their proper positions. There is ___ evidence of a malformation, hemorrhage, focal infarct, or abscess formation. There is ___ apparent neuronal loss or gliosis in any region. Microglial nodules, perivascular inflammation, or viral inclusions are ___ identified. Regions related to cardiopulmonary control (e.g., n. tractus solitarii, dorsal motor nucleus of the vagus, n. paragigantocellularis lateralis, and parabrachial complex) appear ___. The hypoglossal nucleus (tongue control) has ___ microscopic appearance. There ___ gliosis in the following nuclei: ___. Neuronal loss is ___ appreciated in ___ of the sites by qualitative assessment. There is ___ gliosis in the inferior olive: hypertrophic astrocytes (with abundant, eosinophilic cytoplasm) are present in the neuropil, hilum, and amiculum; there is ___ appreciable associated neuronal atrophy or loss. The basis pontis is ___ gliotic, ___ apparent neuronal loss, and ___ acute neuronal necrosis; reactive microglia and axonal spheroids are ___ present. The arcuate nucleus is ___ identified along the ventral surface of the medulla. The degree of myelination is assessed in the following white matter sites: inferior cerebellar peduncle (internal standard), ___; olivary hilum, ___; olivary amiculum, ___; pyramid, ___; corticospinal tract (pons), ___; corticospinal tract (midbrain), ___; central tegmental tract, ___; tractus solitarius, ___; frontopontine fibers (crus pedunculi), ___; temporopontine fibers (crus pedunculi), ___; pontocerebellar fibers, ___. |
| SPINAL CORD: The spinal cord is examined at representative cervical, thoracic, and lumbar levels. It is ___ well-formed, with ___ neuronal differentiation. The anterior and posterior horns, intermediolateral column, and Clarke’s column ___ have a normal histologic appearance. The posterior and anterior roots are ___ well-myelinated and intact. There ___ focal lesions. The degree of myelination is assessed in the following sites: at the cervical level: posterior column, ___; lateral corticospinal tract, ___; at the thoracic level: posterior columns, ___; lateral corticospinal tract, ___; at the lumbar level: posterior columns, ___; lateral corticospinal tract, ___. |
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