scbm 342 systemic pathology - pathobiology.sc.mahidol.ac.th

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SCBM 342 Systemic Pathology

L12: Neuro and musculoskeletal (25-Feb-2018)

Additional information for LAB study

Nisamanee Charoenchon, Ph.D

[email protected]

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1. Brain - Rabies

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Images of the brain showing (left) thin and discoloured cortical ribbon (arrows) and small hippocampus in a 73-year-old man who died of rabies, and (right) normal cortex.

Ref: Human rabies encephalitis following bat exposure: failure of therapeutic coma Robert C. McDermid, Lynora Saxinger, Bonita Lee, Jennie Johnstone, R.T. Noel Gibney, Marcia Johnson and Sean M. Bagshaw CMAJ February 26, 2008 178 (5) 557-561; DOI: https://doi.org/10.1503/cmaj.071326

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Neuroanatomy - Coronoal Brain Slices

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Negri body

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Normal brain histology

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neuropil is defined as the space between neuronal and glial cell bodies that is comprised of dendrites, axons, synapses, glial cell processes, and microvasculature.

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ONE of the characteristic features of the nerve cells is the large number of basophilic “Nissl granules” in the cytoplasm. Electron microscope studies reveal that the “Nissl substance” is composed of electron dense particles and that these occur either in free form among the membrane structures

The most prominent substructure within the nucleus is the nucleolus , which is the site of rRNA transcription and processing, and of ribosome assembly.

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2. Brain- Malaria

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A summary of representative images from the gross examination of the brain in the autopsy series is shown for CM cases.

CM – cerebral malaria

CM1- CM1, early disease the (“sequestration only” pattern)

CM2- CM2, ring hemorrhages and excessive pigment (the classic pattern)

The vast majority of cases, regardless of diagnosis, showed brain swelling with flattened gyri and narrowed sulci (A).

In this example, the brain has the classic “slate gray” to “purple” appearance of CM which is possibly due to malaria pigment within vessels. In all control cases and in a subset of the CM1 cases, the coronal brain slice appeared without discoloration (B).

In the classic CM2 appearance, petechial hemorrhages are seen diffusely in the white matter throughout the brain (C).

A higher magnification demonstrates the abrupt transition from white to gray matter and the lack of hemorrhages in the gray (D).

In a subset of the CM1 cases, the coronal brain slice appeared very discolored (an unexplained phenmenon) and swollen but without petechial hemorrhages (A petechial hemorrhage is a tiny pinpoint red mark that is an important sign of asphyxia caused by some external means of obstructing the airways.) in the cerebral cortex (E).

The had petechial hemorrhages in both the gray and white matter and thus, visible on the surface grossly (F).

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(B,E) Were previously published in part in the Journal of Infectious Diseases (2005) and appear here with express permission (see Milner et al., 2005; White and Silamut, 2005).

REF: ORIGINAL RESEARCH ARTICLE

Front. Cell. Infect. Microbiol., 21 August 2014 | https://doi.org/10.3389/fcimb.2014.00104

The systemic pathology of cerebral malaria in African children

Danny A. Milner Jr et al.

Pediatric cerebral malaria carries a high mortality rate in sub-Saharan Africa. We present our systematic analysis of the descriptive and quantitative histopathology of all organs sampled from a series of 103 autopsies performed between 1996 and 2010 in Blantyre, Malawi on pediatric cerebral malaria patients and control patients (without coma, or without malaria infection) who were clinically well characterized prior to death. We found brain swelling in all cerebral malaria patients and the majority of controls. The histopathology in patients with sequestration of parasites in the brain demonstrated two patterns:

(a) the “classic” appearance (i.e., ring hemorrhages, dense sequestration, and extra-erythrocytic pigment) which was associated with evidence of systemic activation of coagulation and

(b) the “sequestration only” appearance associated with shorter duration of illness and higher total burden of parasites in all organs including the spleen. Sequestration of parasites was most intense in the gastrointestinal tract in all parasitemic patients (those with cerebral malarial and those without).

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3. Osteoarthritis and osteochondroma

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1. CARTILAGE CHANGES localised fibrillation or disruption of the most superficial layers of cartilage.

the surface become roughened and irregular, fibrillation goes deeper, it reaches subchondral bone decrease of cartilage surface enzymatic degradation of the matrix-decrease of cartilage volume

2. BONE CHANGES alterations of the subchondral bone density: formation of cyst- like bone cavities increase of bone density - completely lost of cartilage

3. OSTEOPHYTES* fibrous, cartilagineous and bony prominences develop around the periphery of the joints

4. SECONDARY CHANGES in the synovium, capsules, ligaments and musculs moderate inflammatory reaction.

* a bony outgrowth associated with the degeneration of cartilage at joints.

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Osteoarthritis of the hip is common.

In this typical image, there is marked irregularity and erosion of the articular surface. Very little articular cartilage remains.

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The periarticular bone of diarthrodial joints is organized into distinct structural anatomic components . The bone immediately beneath the articular cartilage is comprised of compact bone that forms a plate-like structure. This bone is separated from the overlying articular cartilage by a zone of calcified cartilage. The interface between the articular and calcified cartilage is demarcated by the so-called “tide-mark” that can be identified by its enhanced metachromatic staining pattern. The bone beneath the subchondral plate is organized into a network of cancellous trabecular bone. The periosteal bone that forms the joint margins is in immediate contact with the joint capsule and synovial lining, beneath which the ligaments and tendons insert into the bone, forming the unique structure of the enthesis.

Ref: Osteoimmunology (Second edition), Interactions of the Immune and Skeletal Systems, 2016, Pages 257–269

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Histopathology:an osteochondroma displays the benign cartilagenous cap at the left upper and the bony cortex at the right lower. This bone growth, though benign, can sometimes cause problems of pain and irratation that lead to removal surgically. It is benigh tumor with very rare incidence of malignant transformation.

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Schematics of dedifferentiation development and the associated features. The difference and development of the osteochondroma (a, H&E in d) to

chondrosarcoma (b, H&E in e)

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Primary cilia organization reflects cell polarity in the growth plate and in sub-populations of osteochondroma cells.

Schematic representation shows the virtual axis that is formed by the alignment of primary cilia and crosses the center of each column of chondrocytes (a, left and right panels).

Chondrocytes of the growth plate are known to divide parallel to the longitudinal axis of the bone (arrow-bar) (b, left panel).

The daughter chondrocytes must undertake a series of cell movements/rotations and shape changes to generate the typical columns of the growth plate and align primary cilia on one common axis (a, b, left panel).

A model is proposed in which an osteochondroma forms as a consequence of chondrocytes losing their ability to move/rotate to re-orient themselves with respect to the growth axis (arrow-bar) (b, right panel).

Interestingly, some sub-populations of osteochondroma cells are able to form columns and to orient the cilium parallel to the longitudinal axis of the tumor (arrow-bar) (a, right panel).

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Ref: Primary cilia organization reflects polarity in the growth plate and implies loss of polarity and mosaicism in osteochondroma

By: de Andrea, Carlos E.; Wiweger, Malgorzata; Prins, Frans; et al. LABORATORY INVESTIGATION Volume: 90 Issue: 7 Pages: 1091-1101 Published: JUL 2010

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Histology of the growth plate and osteochondroma. The growth plate is formed by three zones: resting (RZ), proliferating (PZ) and pre/hypertrophic (HZ) that over time turn into bone (B). Along the growth plate, the chondrocytes undergo proliferation (PZ) and differentiation (HZ and B). During these processes, the cell columnar organization is maintained. Osteochondromas are formed by three layers: outer perichondrium (asterisk), cartilaginous cap and underlying bone.

The histological features of osteochondromas are to some extent similar to the ones of the growth plate. The zonation is less defined (RZ, PZ and HZ), and the cells are irregularly arranged and rarely acquire columnar organization. นน – งอก Hypertrophic-like chondrocytes (arrowhead) are observed within the RZ and PZ. The osteochondroma cells also undergo terminal ossification (B). (RZ, resting zone; PZ, proliferating zone; HZ, hypertrophic zone; Scale bars, 100 μm).

Ref: Dedifferentiated peripheral chondrosarcomas: Regulation of EXT-downstream molecules and differentiation-related genes in Modern Pathology 22(11):1489-98 · October 2009

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Cartilage - capped bony outgrowth up to 10 cm (mean 4 cm), attached to skeleton by bony stalk, not in medullary cavity

May have bursa ถงน าลดการเสยดส around its head Cartilage cap usually regular and thin

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Hyaline cartilage

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4. Meningioma

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Meningothelial (arachnoidal) cells are believed to be the cell of origin of meningiomas.

The arachnoid cells have several proposed functions, including acting as a structural barrier with cellular wrapping/ensheathing, acting as a conduit for cerebrospinal fluid (CSF) drainage/absorption into dural sinuses/veins (arachnoid villi), epithelial-like/secretory functions, monocytelike functions, trophic support and byproduct detoxification for glial and neuronal cells, and participation in reactive/reparative processes.

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Image 1: Benign meningiomas are often round to lobulated dural based masses (A) that are firmly attached to the dura (B). In this particular case, the cut surface is tan, granular, and free of hemorrhage.

Ref: Kar-Ming Fung.2014. Meningiomas Pathology. date of searching: 2nd Feb, 2018. https://emedicine.medscape.com/article/1744164-overview#a1

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Image 2: In the less cellular area of the smear, single neoplastic meningothelial cells are frequently seen, particularly in meningothelial meningioma. These cells have a moderate amount of cytoplasm, elongated to oval nuclei, and delicate, amphophilic cytoplasm. A small meningothelial whorl is present in this image (arrow).


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Image 3: A large meningothelial whorl is present in this image. These whorls are confirmative for the diagnosis of meningioma.


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Image 4: Two psammoma bodies wrapped by neoplastic meningothelial cells are present.


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Image 5: The enlarged secretory vacuoles are well demonstrated in this cytologic preparation (arrow). Note that the vacuoles are several times larger than the nuclei, a feature that distinguishes secretory meningiomas from metastatic mucin producing adenocarcinomas.


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Image 6: The rhabdoid feature of this tumor is well demonstrated in this cytologic preparation. Note the eccentrically located nuclei and the large oval, amphophilic cytoplasm. In this particular case, the nuclear feature is rather bland for a rhabdoid tumor. The nuclei of rhabdoid tumors can be rather bizarre featuring enlarged, lobulated nuclei with huge, eosinophilic nucleoli.


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Image 7: A psammoma body is present in the meningothelial meningioma. Psammoma bodies are usually not numerous in meningothelial meningiomas.


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Image 8: In WHO grade I meningothelial meningioma, the nuclear size is rather uniform, oval in shape, with open chromatin and without prominent nucleoli. The cytoplasmic border is typically indistinct. Abundant intranuclear pseudoinclusions and intranuclear clear vacuoles are present in this image.

Benign meningioma (WHO grade I) WHO grade I meningiomas are defined by the following: Histologic variant other than clear cell, chordoid, papillary, and rhabdoid Lacks criteria of atypical and anaplastic meningioma

Atypical meningioma (WHO grade II) Any of the following 3 criteria are used for WHO grade II meningiomas: Mitotic index of ≥4/10 HPFs * At least 3 of the 5 following parameters: (1) sheeting architecture (loss of whorling and/or fascicles), (2)

small cell formation (high nucleus-to-cytoplasmic [N/C] ratio), (3) macronucleoli, (4) hypercellularity, or (5) spontaneous necrosis (ie, not induced by embolization or radiation)

Brain invasion †


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Image 9: In comparison to Image 8, the cells in this tumor do not appear epithelioid and have far lower frequency of intranuclear pseudoinclusions (arrow). The abundance of intranuclear clear vacuoles and intranulcear pseudoinclusion can be quite variable among different tumors.


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Image 10: This fibroblastic meningioma has all the features of a benign or low-grade spindle cell tumor. A substantial amount of collagen fibers are present. The psammoma body is a good clue suggesting meningioma.


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Image 11:In this case of transitional meningioma, the features are somewhat between those of a meningothelial meningioma and those of a fibroblastic meningioma. A moderate amount of collagen is present in the areas with fibroblastic features. Well formed meningothelial whorls are present.


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Image 12: High magnification of Image 11 and details of well formed meningothelial whorls are shown here.


scbm 342 systemic pathology - pathobiology.sc.mahidol.ac.th

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