DE LA SALLE HEALTH SCIENCES INSTITUTE COLLEGE OF MEDICINE BATCH 2013

Prepared by: Liaa Brigola Rencel Faustino Ballares Migs Maralit

PATHOLOGY 8TH EVALUATION

Contents: I. CNS PATHOLOGY II. CLINICAL PATHOLOGY: CSF, SEROUS BODY FLUIDS & SEMENALYSIS II. MUSCULO SKELETAL PATHOLOGY III. ENVIRONMENTAL & NUTRITIONAL PATHOLOGY CNS PATHOLOGY MULTIPLE CHOICE 1. The most common cause of non-traumatic intracerebral hemorrhage is: a. trauma b. ruptured vascular malformation c. bleeding of an intracerebral tumor d. hypertensive cerebrovascular disease 2. The following are causes of non-communication hydrocephalus, EXCEPT: a. congenital stenosis of the aqueduct b. intraventricular hemorrhage c. choroid plexus papilloma d. post-TB meningitis with arachnoid fibrosis e. none of the above Non-communication (obstructive)Hydrocephalus- block in the CSF pathway within the brain; block aqueducts; eg stenosis of aqueduct/ tumor within ventricle Communicating Hydrocephalus- CSF is able to pass the subarachnoid space; obstruction at the subarachnoid space; eg post meningitis 3. The following are characteristic clinical and pathologic findings in uncal (transtentorial) herniation, EXCEPT: a. papillary dilatation b, impaired ocular movement on the side of the lesion c. Duret hemorrhages d. occipital hemorrhagic infarcts e. none of the above 4. The most common type of vascular malformation of the brain: a. arterio-venous malformation b. cavernous angioma c. capillary talengiectasia d. venous angioma

5. The following are characteristic microscopic findings in viral encephalitis, EXCEPT: a. perivascular mononuclear infiltrate b.microglial nodules c. neuronophagia d. intracytoplasmic viral inclusions e. none of the above Most characteristic histologic features:

-perivascular and parenchymal mononuclear cell infiltrates (lymphocytes, plasma cells and macrophage) - glial cell reactions (including formation of microglial nodules) -neurophagia Direct indication of viral infection: presence of viral inclusion bodies and identification of viral pathogens 6.The following are characteristic clinical and pathologic findings in TB meningoencephalitis, EXCEPT: a. ischemic infarcts b. caseating granulomas c. cranial nerve palsies d. exudates predominantly along the convexities acute pyogenic meningitis e. none of the above Microscopic findings: caseating granulomas; ischemic infarcts due to obliterative arteritis; mixture of lymphocytes, plasma cells and macrophages Clinical findings: chronic course; cranial nerve palsies; focal deficits (due to infarcts)

7. Neuritic plaques and neurofibrillary tangles are characteristic of: a. Parkinsons disease b. Huntingtons disease c. Alzheimers disease d. Multiple sclerosis Alzheimers disease is the most common cause of dementia in the elderly. Gross features: cortical atrophy (narrowed gyri and widened sulci) and hydrocephalus ex vacuo Histologic features: neuritic plaques, neurofibrillary tangles and amyloid angiopathy 8. This disease is characterized by atrophy of the caudate nucleus, putamen and globuspallidus a. Parkinsons disease b. Huntingtons disease c. Alzheimers disease d. Multiple sclerosis Huntington disease is an inherited autosomal dominant disease characterized clinically by progressive movement disorders and dementia with degeneration of the striatum (caudate and putamen). 9. Skull fracture with tear of the middle meningeal artery results in: a. epidural hematoma b. subdural hematoma c. intracerebral hemorrhage d. subarachnoid hemorrhage Epidural hematoma- tear of the meningeal artery, usually with skull fracture in adults; may develop in children even without fracture. Subdural hematoma- blunt trauma without skull fracture with tear of bridging veins. Intracerebral hemorrhage- most commonly due to hypertension usually in the basal ganglia. Subarachnois hemorrhage- due to the ruptured berry (saccular) aneurysm (involves junction between anterior communicating artery and anterior cerebral artery). Due to hypertension, coarctation of the aorta. 10. The end result of repair in the CNS: a. fibrosis b. gliosis c. satellitosis d. neuronophagia

BATCH 2013 PATHOLOGY | 8TH EVALUATION

Glial cells- provides support and function for neurons; primary role in repair, fluid balance and energy metabolism. Gliosis- hypertrophy and hyperplasia; glial scar formation: occurrence of overgrowth of the neuroglia, proliferation if fibrillary astrocytes with the formation of glial cells as a reaction to CNS injury. Neuronophagia: proliferation of microglial cells around degenerating or dead neurons 11. An intracranial tumor arising from arachnoid cells and is most commonly parasagittal in the location: a. schwannoma b. meningioma c. oligodendroglioma d. ependymoma Schwannomas: benign tumors that rarely become malignant; arise from the neural crest derived Schwann cells Meningiomas: adults; arise from arachnoid villi, attached to dura Oligodendroglioma- adults/ cerebellum Ependymomma- children/ periventricular; adults/ spinal cord 12. The principal manifestation of degenerative disease of the cerebral cortex: a. ataxia b. chorea c. dementia d. tremors Degenerative diseases affecting the cerebral cortex is charatecterized by dementia (impairment on intellectual function); Alzheimers disease 13. A highly malignant primary brain neoplasm characterized by pseudopalisading necrosis of endothelial hyperplasia neurons: a. medulloblastoma b. glioblastoma c. anaplastic astrocytoma d. anaplastic oligodendroglioma 14. The most common primary source of metastatic carcinoma to the brain in a female: a. lungs b. stomach c. breast d. ovary 15. A congenital malformation characterized by failure of cephalic portion of the neural tube to develop resulting in the absence of brain and calvarium: a. encephalocele b. myelocele c. Arnold-Chiari malformation d. anencephaly Encephalocele- seen in occipital area and meningoencephalocoele Arnold-Chiari malformation- with elongation of the cerebellar tonsils and drawing of the cerebellum into the 4th ventricle forming a cyst lined with ependyma covered by meninges; hydrocephalus is always present. Anencephaly- most common neural tube defect; failure of the cranial (rostral) part to develop. 16. A highly malignant childhood neoplasm occurring exclusively in the cerebellum and arising from poorly differentiated neuroectodermal cells:

BATCH 2013 PATHOLOGY | 8TH EVALUATION

a. anaplastic ependymoma b. neuroblastoma c. medulloblastoma d. glioblastoma 17. Multiple well-defined nodules in the brain occurring in the junction of the gray and white matter are most likely: a. metastatic carcinoma b. tuberculoma c. cysticercosis d. glioblastoma MUSCULO SKELETAL SYSTEM MULTIPLE CHOICE 18. Developmental anomalies resulting from localized problems in the migration of mesenchymal cells and the formation of condensation is called ___ and best exemplified by ___. a. Dysostoses, Aplasia b. Dysplasia, Achondroplasia c. Anaplasia, Carcinoma d. Dysplasia, CIN 2 Rationale: Developmental anomalies resulting from localized problems in the migration of the mesenchymal cells and the formation of the condensations are known as dysostoses. They are usually limited to defined embryologic structures and may result from mutations in certain transcription factors (e.g., homeobox genes). In contrast, mutations in the regulators of skeletal organogenesis, such as signaling molecules (e.g., growth factors and their receptors) and matrix components (e.g., types 1 and 2 collagen) affect cartilage and bone tissues globally; these disorders are known as dysplasias Source: Robbins 8th ed. Chapter 26 19. Mutations that interfere with bone or cartilage growth and/or maintenance of normal matrix components having more diffuse effects is called __ and best exemplified by _. a. Dysostoses, Osteopetrosis b. Dysplasia, Osteogenesis imperfecta c. Dysplasia, Agenesis d. Dysplasia, Supernumerary digits R: Mutations in the regulators of skeletal organogenesis, such as signaling molecules (e.g., growth factors and their receptors) and matrix components (e.g., types 1 and 2 collagen) affect cartilage and bone tissues globally are known as dysplasias. Source: Robbins 8th ed. Chapter 26 20. Osteogenesis imperfecta, a generalized bone defect with diffuse effects is: a. Also known as brittle bone disease b. Caused by defective synthesis of type II collagen c. Fundamental abnormality characterized by too much bone d. All of the above R: Osteogenesis imperfecta brittle bones, defective synthesis of type I collagen, too little bone S: Robbins 8th ed. Chapter 26 21. Achondroplasia: a. Major cause of dwarfism b. Is a point mutation in the fibroblast growth factor c. Causes disproportionate shortening of the proximal extremities d. All of the above

BATCH 2013 PATHOLOGY | 8TH EVALUATION

R: Achondroplasia - most common disease of the growth plate major cause of dwarfism - caused by a mutation in the FGF receptor 3 (FGFR3). Normally, FGFmediated activation of FGFR3 inhibits cartilage proliferation; in achondroplasia, the mutations cause constitutive activation of FGFR3 and thereby suppress growth. - Manifestations: shortened proximal extremities, trunk of relative normal length, enlarged head with bulging forehead, conspicuous depression of the root of the nose. Source: Robbins 8th ed. Chapter 26 22. Osteopetrosis characterized by reduced osteoclast-mediated bone resorption a. Results in defective bone remodelling b. Is associated with carbonic anhydrase II deficiency in some variants c. Is also known as stone bone or marble bone disease A.K.A Albers-Schnberg disease d. All of the above R: Osteopetrosis aka marble bone disease and Albers-Schnberg disease - characterized by reduced bone resorption and diffuse symmetric skeletal sclerosis due to impaired formation or function of osteoclasts (results in defective bone remodelling) - reflects the stonelike quality of the bones; however, the bones are abnormally brittle and fracture easily, like a piece of chalk. - Associated with carbonic anhydrase II deficiency S: Robbins 8th ed. Chapter 26 23. Osteoporosis a. Is characterized by decreased porosity of the skeleton resulting to reduced bone mass b. Senility is the most common form c. Is most conspicuous in compact bones d. Histologically show thickened trabeculae and vanishing Haveresian systems e. All of the above R: Osteoporosis - characterized by porous bones and a reduced bone mass predispose the bone to fracture MC form: senile and postmenopausal osteoporosis, in which the loss of bone mass makes the skeleton vulnerable to fractures increase in osteoclast activity affects mainly bones or portions of bones that have increased surface area, such as the cancellous compartment of vertebral bodies. trabecular plates become perforated, thinned, and lose their interconnections, leading to progressive microfractures and eventual vertebral collapse. cortex is thinned by subperiosteal and endosteal resorption, and the haversian systems are widened th S: Robbins 8 ed. Chapter 26 24. Infectious arthritis affecting children under 2 years of age: a. Gonococcal arthritis late adolescence and young adulthood b. H. influenzae arthritis c. Tuberculous arthritis -occurs in all age groups, especially adults d. Staphylococcal arthritis older children and adults

BATCH 2013 PATHOLOGY | 8TH EVALUATION

R: Hemophilus affects children <2 y/o Staphylococcus older children and adult Gonococcus late adolescence and young adulthood S: Robbins 8th ed. Chapter 26 25. Insidious arthritides usually hematogenously spread from a primary focus manifesting as a cold abscess a. Gonococcal arthritis b. H. influezae arthritis c. Tuberculous arthritis d. Staphylococcal arthritis R: Tuberculous arthritis - chronic progressive monoarticular disease that occurs in all age groups, especially adults - usually develops as a complication of adjoining osteomyelitis or after hematogenous dissemination from a visceral (usually pulmonary) site of infection - insidious onset and causes gradual progressive pain - induces formation of confluent granulomas with central caseous necrosis - affected synovium may grow as a pannus over the articular cartilage and erode the bone along the joint margins - chronic disease: severe destruction with fibrous ankylosis and obliteration of the joint space - weight-bearing joints are usually affected, especially the hips, knees, and ankles in descending order of frequency. S: Robbins 8th ed. Chapter 26 26. Most common soft tissue tumor of adulthood a. Ganglion cyst b. Lipoma c. Myositis ossificans in athletic adolescents and young adults and follows an episode of trauma d. Neurofibroma R: Lipoma - the most common soft-tissue tumor of adulthood - well-encapsulated mass of mature adipocytes that varies considerably in size - arises in the subcutis of the proximal extremities and trunk, most frequently during middle adulthood - large, intramuscular, and poorly circumscribed - soft, mobile, and painless (except angiolipoma) and are usually cured by simple excision S: Robbins 8th ed Chapter 26 27. Most common soft tissue malignancy of childhood and adolescence a. Synovial sarcoma -fourth most common sarcoma b. Liposarcoma -one of the most common sarcomas of adulthood c. Fibrosarcoma d. Rhabdomyosarcoma e. Malignant Fibro-Histiocytic Tumor -most common sarcoma of adults R: Rhabdomyosarcoma - most common soft-tissue sarcoma of childhood and adolescence, usually appears before age 20 - most occur in the head and neck or genitourinary tract, where there is little if any skeletal muscle as a normal constituent - is histologically subclassified into embryonal, alveolar, and pleomorphic variants

BATCH 2013 PATHOLOGY | 8TH EVALUATION

rhabdomyoblastthe diagnostic cell in all typescontains eccentric eosinophilic granular cytoplasm rich in thick and thin filaments - rhabdomyoblasts may be round or elongate; the latter are known as tadpole or strap cells, and may contain cross-striations visible by light microscopy - rhabdomyoblasts contain sarcomeres, and immunohistochemically they stain with antibodies to the myogenic markers desmin, MYOD1, and myogenin S: Robbins 8th ed. Chapter 26 28. Malignant spindle cells arranged in herringbone pattern a. Synovial sarcoma b. Liposarcoma c. Fibrosarcoma fascicles d. Rhabdomyosarcoma e. Malignant Fibro

R: Fibrosarcoma - most common in the deep soft tissues of the extremities - unencapsulated, infiltrative, soft, fish-flesh masses often having areas of hemorrhage and necrosis - disclose all degree of differentiation from slowly growing tumor that closely resemble cellular fibromatosis and sometimes having spindled cells growing in a herringbone fashion to highly cellular neoplasms dominated by architectural disarray, pleomorphism, frequent mitoses, and areas of necrosis - are aggressive tumors, recurring in more than 50% of cases and metastasizing in more than 25% S: Robbins 8th ed. Chapter 26 29. Fascicle s of plump spindle cells in swirling storiform pattern a. Synovial sarcoma b. Liposarcoma c. Fibrosarcoma d. Rhabdomyosarcoma e. Malignant Fibro R: Malignant Fibrous Histiocytoma is a group of soft-tissue tumors characterized by considerable cytologic pleomorphism, the presence of bizarre multinucleate cells, and storiform architecture. S: Robbins 8th ed. Chapter 26 30. Tumor cells with differentiation both in epithelial-like and spindly cells a. Synovial sarcoma b. Liposarcoma c. Fibrosarcoma d. Rhabdomyosarcoma e. Malignant Fibro-HistiocyticTumor R: Synovila sarcoma - histologic hallmark: dual lines of differentiation (i.e., epithelial-like and mesenchymal-like) - the epithelial cells are cuboidal to columnar and form glands or grow in solid cords or aggregates. The spindle cells are arranged in densely cellular fascicles that surround the epithelial cells - (+) calcified concretions that can sometimes be detected radiographically - yield positive reactions for keratin and epithelial membrane antigen

BATCH 2013 PATHOLOGY | 8TH EVALUATION

- sites of metastases: lung, skeleton, and occasionally regional lymph nodes S: Robbins 8th ed. Chapter 26

CLINICAL PATHOLOGY: CSF, SEROUS BODY FLUIDS & SEMENALYSIS 31. Which of the following findings is indicative of bacterial meningitis? a. decrease glucose, decrease protein, increased neutrophils b. increased glucose, increased protein, increased neutrophils c. decreased glucose, increased protein, increased neutrophils d. increased glucose, increased protein, decreased neutrophils e. none of the above Protein: normal 15-25 mg/dL; elevated in meningitis, hemorrhage and MS Glucose: normal 60-70% of plasma concentration; decreased in bacterial, fungal, tubercular meningitis Lactate: normal 10-22 mg/dL; levels > 35 mg/dL bacterial; levels >25 tubercular, fungal meningitis Glutamine: normal 8-18 mg/dL; >35 mg/dL associated with disturbance of consciousness 32. Which of the following is correct regarding CSF analysis? a. bottle #1: chemistry, bottle #2: microbiology, bottle#3: cell count and differential b. bottle # 1: microbiology, bottle #2: chemistry, bottle #3: cell count and differential c. bottle #1: cell count and differential, bottle #2: microbiology, bottle #3: chemistry d. bottle #1: microbiology, bottle #2: cell count and differential, bottle #3: chemistry Test tube #1: chemistry and immunologic studies (used for lactate, proteins and sugar Test tube #2: microbiologic exam (for culture, gram stain, AFB or fungal examination) Test tube #3: cell count and differential count 33. Proper collection of a semen specimen should include all of the following method of collection, EXCEPT: a. specimen is placed in a sterile container b. collection after a three day period of sexual abstinence c. collection at the laboratory, followed by one hour of refrigeration d. collection maybe done at home, but delivered to the laboratory within one hour collection of semen: 3 day period of abstinence; sterile container; note time of specimen collection; if collection room is not available, keep specimen in room temperature and deliver to laboratory within 1 hour; fresh specimen is collected and should liquefy within 30 minutes after collection; begin analysis once liquefaction has occurred 34. Semen sample should be analyzed: a. immediately upon receipt b. prior to liquefaction c. after liquefaction d. one hour after collection Fresh specimen is collected and should liquefy within 30 minutes after collection; begin analysis once liquefaction has occurred 35. An abnormal amount of prostatic fluid in a semen specimen will: a. lower the pH b. raise the pH c. increased the viscosity d. decreased the viscosity

BATCH 2013 PATHOLOGY | 8TH EVALUATION

Increased viscosity or incomplete liquefaction will interfere with sperm motility. High ratio or prostatic fluid to a seminal fluid will produce an acidic pH 36. The purpose of diluting semen specimens prior to counting is to: a. ensure liquefaction of the specimen b. allow motility to be determined while performing the count c. enhanced the cellular morphology d. immobilize and preserve the sperm Examine undiluted specimen and determine the percentage of sperm showing active motility. 37. The presence or absence of semen in a specimen can accurately be done testing for: a. fructose b. alkaline phospatase c. acid phosphatase d. antibodies Acid phosphatase activity: determines secretory function of the prostate gland; may be used in forensic studies to determine presence of seminal fluid. A. Acute pyogenic meningitis B. Tuberculous meningitis A B B A B 38. CSF findings: moderately increased protein, markedly decreased sugar 39. CSF findings: markedly increased protein, moderately increased sugar 40. exudate, predominantly basal 41. exudate, predominantly along the cerebral convexities 42. hydrocephalus, cranial nerve palsy and ischemic infarcts, common

Acute pyogenic meningitis: there are acute inflammatory cells in the subarachnoid space. CSF findings include increase pressure (cloudy or purulent CSF), increased WBC (predominantly mononuclears), increased protein, markedly decreased sugar (bacteria use up the sugar) and positive bacteria on gram stain and culture Tuberculous meningitis: exudates predominantly basal. Arachnoid fibrosis may produced hydrocephalus and obliterative endateritis causing arterial occlusion and infarction of the underlying brain. CSF findings include increase pressure, increased WBC (predominantly lymphocytes), markedly increase protein (characteristic of TB meningitis) and decrease sugar. CNS PATHO MATCHING TYPE A. B. C. D. C B A C Uncal herniation Tonsillar herniation Both A and B Neither A nor B

43. increased intracranial pressure 44. infratentorial neoplasm 45. unilateral fixed dilated pupil and diplopia 46. potentially fatal

Uncal (Transtentorial) Herniation herniation of the medial temporal lobe under the free edge of the tentorium; it usually affects the midbrain MIDBRAIN COMPRESSION; CN III and IV as well as post cerebral artery are affected causing papillary dilatation, visual disturbance and abnormal eye movement.

BATCH 2013 PATHOLOGY | 8TH EVALUATION

Tonsillar (Cerebellar) Herniation herniation or the cerebellar tonsils into the foramen magnum; manifests affects on the CVS and repiratory center in the medulla. A. Global cerebral ischemia B. Focal cerebral ischemia C. Both A and B D. Neither A or B 47. red neuron 48. shock and cardiac arrest, underlying causes 49. thrombi and emboli, underlying causes 50. watershed infarcts

C A B A

Global cerebral ischemia (Ischemic/Hypoxic Encephalopathy) Cause -generalized reduction of cerebral perfusion -watershed or borderzone infarcts occur with reduced perfusion in those regions of the brain and spinal cord that lie at the most edges of arterial supply -circulatory and oxygen deficiency Morphology Gross: swollen (edematous) brain, poor demarcation between gray and white matter Micro: ischemic cell change (red neurons); watershed infarcts Focal cerebral ischemia (cerebral infarction) -a localized area of ischemic necrosis -thrombotic stenosis/occlusion due to atherosclerosis, embolism and arteritis Morphology Gross: early- pale (bland) infarcts usually artherosclerotic; late- cystic cavity because the brain has undergone liquefaction already. Micro: early- red neurons; late- polys, glitter cells gliosis liquefactive necrosis leaving a central ischemic area (presence of inflammatory cells like macrophage) A. B. C. D. C D A B D WHO I/IV WHO II/IV WHO III/ IV WHO IV/IV

51. Anaplastic Astrocytoma 52. Glioblastoma 53. Pilocytic Astrocytoma 54. Epedymoma 55. Medulloblastoma

Primary Neoplasm 1. Gliomas 1.1 Astrocytoma a. Fibrillary (diffuse) Astrocytoma a.1 well differentiated fibrillary astrocytoma (II/IV) a.2 anaplastic astrocytoma (III/IV) a.3 glioblastoma (IV/IV) variants: pilocytic astrocytoma (I/IV), gemistocytic astrocytoma (II/IV) b. Pleomorphic Xanthoastrocytoma (II/IV) c. Brainstem glioma (II-IV/IV) 1.2 Oligodendroglioma (II/IV) a. Anaplastic oligodendroglioma (III/IV) 1.3 Ependymoma (II/IV) a. Anaplastic ependymoma (III/IV) b. Myxopapillary ependymoma (I/IV)

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2.

3.

c. Choroid plexus papilloma (I/IV) d. Colloid cyst Neuronal Tumors a. Gangliocytoma b. Ganglioglioma (II/IV) c. Cerebral neuroblastoma Poorly Differantiated Neoplasms a. Medulloblastoma (IV/IV) b. Atypical teratoid/Rhabdoid tumor (IV/IV)

A. Intracerebral hemorrhage B. Traumatic tap A 56. even distribution of blood in all three tubes A 57. xanthochromic supernatant B 58. specimen contains clots Features Distribution of blood Xanthocromia Erythrophagia and hemosiderin laden macrophages Clot formation Traumatic tap 1>2>3 + + Subarachnoid Hemorrhage/ Pathologic Bleed Even in all tubes - (supernatant is pale yellow) + -

MUSCULO SKELETAL SYSTEM MATCHING TYPE A. B. C. D. E. 59. 60. 61. 62. Brown tumor Ischemia with resultant infarcts Vitamin D deficiency Decreased excretion of Phosphates Mosaic pattern in woven or lamellar bone E C A B

Pagets disease of the bone Rickets / Osteomalacia Hyperparathyroidism Osteonecrosis

#59-62 Ratio (source: Robbins 8th ed. Chapter 26 ) Pagets disease (osteitis deformans) - can be divided into three phases; (1) an initial osteolytic stage, followed by (2) a mixed osteoclastic-osteoblastic stage, which ends with a predominance of osteoblastic activity and evolves ultimately into (3) a burnt-out quiescent osteosclerotic stage - net effect is a gain in bone mass; however, the newly formed bone is disordered and architecturally unsound - usually begins in late adulthood (average age at diagnosis, 70 years) - hallmark is the mosaic pattern of lamellar bone. This pattern, which is likened to a jigsaw puzzle, is produced by prominent cement lines that anneal haphazardly oriented units of lamellar bone Rickets/ Osteomalacia - characterized by a defect in matrix mineralization - most often related to a lack of vitamin D or some disturbance in its metabolism

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Rickets - refers to the disorder in children in which deranged bone growth produces distinctive skeletal deformities Osteomalaci in adults, because the bone that forms during the remodeling process is inadequately mineralized this results in osteopenia and predisposition to insufficiency fractures

Hyperparathyroidism - increased PTH concentrations are detected by receptors on osteoblasts, which then release factors that stimulate osteoclast activity - skeletal manifestations of hyperparathyroidism are caused by unabated osteoclastic bone resorption - affects cortical bone (subperiosteal, osteonal, and endosteal surfaces) more severely than cancellous bone - osteoclasts tunnel into and dissect centrally along the length of the trabeculae, creating the appearance of railroad tracks and producing what is known as dissecting osteitis - The bone loss predisposes to microfractures and secondary hemorrhages that elicit an influx of macrophages and an ingrowth of reparative fibrous tissue, creating a mass of reactive tissue, known as a brown tumor. The brown color is the result of the vascularity, hemorrhage, and hemosiderin deposition, and it is not uncommon for the lesions to undergo cystic degeneration - the combined picture of increased bone cell activity, peritrabecular fibrosis, and cystic brown tumors is the hallmark of severe hyperparathyroidism and is known as generalized osteitis fibrosa cystica (von Recklinghausen disease of bone). Osteonecrosis - caused by ischemia with resultant medullary infarcts in the cancellous bone and marrow - Infarction of bone and marrow is a relatively common event that can occur in the medullary cavity of the metaphysis or diaphysis and the subchondral region of the epiphysis - (+) creeping substitution Pagets disease Mosaic pattern Rickets Vitamin D deficiency Seen in children Frontal bossing Rachitic rosary Pigeonbreast *Table from Nicole Ocampo Osteomalacia Vitamin D deficiency Milkmans fracture Block in normal mineralization of osteoid Hyperparathyroidism Brown tumor Osteonecrosis Ischemia with resultant infarcts Medullary infarcts Creeping substitution

a.k.a osteitis deformans Cause by paramyxovirus Leonine facies Anterior bowing of femur and tibia

Increase parathormone cortical cutting cones

1. 2. 3. 4. 5. 63. 64. 65. 66.

Osteoarthritis Rheumatoid arthritis Pseudogout Gout All of the above E D A B

Destruction of articular cartilage Tophus Heberdens nodes Pannus

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67. 68. 69. 70.

Chondrocalcinosis Affects proximal joints of non-weight bearing joints Affects predominantly weight-bearing joints of the elderly Calcium pyrophospahate
th

C B A C

#63-70 Ratio (source: Robbins 8 ed. Chapter 26 ) Osteoarthritis - also called degenerative joint disease, is the most common type of joint disease and is characterized by the progressive erosion of articular cartilage - appears insidiously, without apparent initiating cause, as an aging phenomenon (idiopathic or primary osteoarthritis) - is usually oligoarticular (affects few joints) but may be generalized - morphology: o chondrocytes proliferate, forming clusters o water content of the matrix increases and the concentration of proteoglycans decreases o vertical and horizontal fibrillation and cracking of the matrix occur as the superficial layers of the cartilage o Type 2 collagen molecules are degraded - Grossly this manifests as a granular soft articular surface. - The dislodged pieces of cartilage and subchondral bone tumble into the joint, forming loose bodies (joint mice) The exposed subchondral bone plate becomes the new articular surface, and friction with the opposing degenerated articular surface smooths and burnishes the exposed bone, giving it the appearance of polished ivory (bone eburnation) - There is rebuttressing and sclerosis of the underlying cancellous bone and small fractures - Symptoms include deep, achy pain that worsens with use, morning stiffness, crepitus, and limitation of range of movement. Impingement on spinal foramina by osteophytes results in cervical and lumbar nerve root compression and radicular pain, muscle spasms, muscle atrophy, and neurologic deficits - Typically, only one or a few joints are involved - The joints commonly involved include the hips, knees, lower lumbar and cervical vertebrae, proximal and distal interphalangeal joints of the fingers, first carpometacarpal joints, and first tarsometatarsal joints of the feet (weight bearing joints) Heberden nodes, prominent osteophytes at the distal interphalangeal joints, are common in women (but not in men) Rheumatoid Arthritis - a chronic systemic inflammatory disorder that may affect many tissues and organsskin, blood vessels, heart, lungs, and musclesbut principally attacks the joints, producing a nonsuppurative proliferative and inflammatory synovitis that often progresses to destruction of the articular cartilage and ankylosis of the joints - histologic features include: o infiltration of synovial stroma by a dense perivascular inflammatory infiltrate composed of lymphoid aggregates (mostly CD4+ helper T cells), B cells, plasma cells, dendritic cells, and macrophages o increased vascularity due to vasodilation and angiogenesis, with superficial hemosiderin deposits o aggregation of organizing fibrin covering portions of the synovium and floating in the joint space as rice bodies o accumulation of neutrophils in the synovial fluid and along the surface of synovium but usually not deep in the synovial stroma o osteoclastic activity in underlying bone, allowing the synovium to penetrate into the bone and cause juxta-articular erosions, subchondral cysts, and osteoporosis

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pannus formation - a mass of synovium and synovial stroma consisting of inflammatory cells, granulation tissue, and synovial fibroblasts, which grows over the articular cartilage and causes its erosion. In time, after the cartilage has been destroyed, the pannus bridges the apposing bones to form a fibrous ankylosis, which eventually ossifies and results in bony ankylosis. symmetrical and the small joints are affected before the larger ones. Symptoms usually develop in the hands (metacarpophalangeal and proximal interphalangeal joints) and feet, followed by the wrists, ankles, elbows, and knees. Uncommonly the upper spine is involved, but the lumbosacral region and hips are usually spared. radiographic hallmarks are joint effusions and juxta-articular osteopenia with erosions and narrowing of the joint space with loss of articular cartilage

Pseudogout - aka Calcium pyrophosphate crystal deposition disease (CPPD)and chondrocalcinosis - one of the more common disorders associated with intra-articular crystal formation - the knees, followed by the wrists, elbows, shoulders, and ankles, are most commonly affected Gout is marked by transient attacks of acute arthritis initiated by crystallization of urates within and about joints, leading eventually to chronic gouty arthritis and the appearance of tophi morphologic changes: o acute arthritis o chronic tophaceous arthritis o tophi - pathognomonic hallmark of gout. They are formed by large aggregations of urate crystals surrounded by an intense inflammatory reaction of macrophages, lymphocytes, and large foreign body giant cells, which may have completely or partially engulfed masses of crystals o gouty nephropathy

71 and 76. Failure of normal bone elements to differentiate into mature structures Fibrous dysplasia benign Fibrous dysplasia - is a benign tumor that has been likened to a localized developmental arrest; all of the components of normal bone are present, but they do not differentiate into their mature structures - it arises during skeletal growth and development, and appear in three distinctive but sometimes overlapping clinical patterns: (1) involvement of a single bone (monostotic); (2) involvement of multiple bones (polyostotic); and (3) polyostotic disease - associated with caf-au-lait skin pigmentations and endocrine abnormalities, especially precocious puberty - mutation in GNAS gene

72and 77. Cartilage capped outgrowth at epiphyseal growth plates Osteochondroma benign Osteochondroma - aka exostosis, is a benign cartilage-capped tumor that is attached to the underlying skeleton by a bony stalk - is the most common benign bone tumor - M>F - develop only in bones of endochondral origin and arise from the metaphysis near the growth plate of long tubular bones - are sessile or mushroom shaped - The cap is composed of benign hyaline cartilage varying in thickness and is covered peripherally by perichondrium. The cartilage has the appearance of disorganized growth

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plate and undergoes enchondral ossification, with the newly made bone forming the inner portion of the head and stalk. 73 and 78. MC form of skeletal malignancy Metastatic lesion malignant Malignant lesions are the most common form of skeletal malignancy usually develop in later stages of tumor progression mode of spread: (1) direct extension, (2) lymphatic or hematogenous dissemination, and (3) intraspinal seeding (via the Batson plexus of veins). metastases originate from cancers of the prostate, breast, kidney, and lung. In children, metastases to bone originate from neuroblastoma, Wilms tumor, osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma. skeletal metastases are typically multifocal most involve areas are the axial skeleton (vertebral column, pelvis, ribs, skull, sternum), proximal femur, and humerus metastases to the small bones of the hands and feet are uncommon and usually originate from cancers of the lung, kidney, or colon.

74 and 79. Composed of mixture of neoplastic mononuclear and reactive osteoclastic-like cells Giant cell tumor neoplasm of uncertain malignant potential Giant Cell Tumor - it contains a mixture of mononuclear cells and a profusion of multinucleated osteoclasttype giant cells, giving rise to the synonym osteoclastoma - is a relatively uncommon benign but locally aggressive neoplasm - usually arises in individuals in their 20s to 40s - the mononuclear cells in giant-cell tumors express RANKL - morphology: o are large, red-brown tumors that frequently undergo cystic degeneration o mostly composed of uniform oval mononuclear cells that constitute the proliferating component of the tumor and numerous scattered osteoclast-type giant cells having 100 or more nuclei that resemble those of the mononuclear cells o (+) necrosis, hemorrhage, hemosiderin deposition, and reactive bone formation - Adults - involve both the epiphyses and the metaphyses - Adolescents - confined proximally by the growth plate and are limited to the metaphysic 75 and 80. Painful enlarging bulky destructive mass of the knee, with codmans triangle as a radiologic exam feature osteosarcoma malignant Osteosarcoma - is a malignant mesenchymal tumor in which the cancerous cells produce bone matrix - most common primary malignant tumor of bone, exclusive of myeloma and lymphoma - bimodal age distribution - <20 y/o and elderly; M > F - tumors usually arise in the metaphyseal region of the long bones of the extremities, and almost 50% occur about the knee - Gross: big bulky tumors that are gritty, gray-white, and often contain areas of hemorrhage and cystic degeneration - The tumor frequently breaks through the cortex and lifts the periosteum, resulting in reactive periosteal bone formation. The triangular shadow between the cortex and raised ends of periosteum is known radiographically as Codman triangle and is characteristic but not diagnostic of this tumor. - spread hematogenously. Metastasis to lungs, bone, brain, elsewhere. -

BATCH 2013 PATHOLOGY | 8TH EVALUATION

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ENVIRONMENTAL & NUTRITIONAL PATHOLOGY

A. Niacin deficiency (B3) B. Vinyl Chloride C. Asbestos D. Carbon monoxide poisoning E. Acetaminophen F. Caisons G. Riboflavin (B2) H. Vitamin C (deficiency) I. Vitamin D J. Thiamin deficiency (B1) K. Aspirin L. Alcohol (Ethanol) M. Lead N. Obesity O. Kwashiorkor P. Marasmus Q. Cobalamin deficiency (B12) R. Vitamin K (deficiency) S. Trench Feet T. Iron U. Frost bite V. Bulimia Nervosa W. Anorexia nervosa X. Heat Cramps Y. Heat Exhaustion Z. Heat Stroke Legend:

Diarrhea, dermatitis, dementia (Pellagra) Angiosarcoma of liver Mesothelioma Cherry red discoloration (seen in acute poisoning) Rhabdomyolysis and renal failure Hepatic Necrosis Bends, chokes, aseptic necrosis Cheilosis, stomatitis, glossitis, dermatitis, corneal vascularization Inadequate formation of osteoid matrix, hemorrhages, impaired wound healing Pigeon breast deformity, Rachitic rosary, frontal bossing, harrisons groove Retrograde Amnesia, Wernick- korsakoff syndrome Renal papillary necrosis(analgesic nephropathy), bleeding tendency, Gastritis (acute, erosive), CNS Syndrome Microcephaly , growth retardation, facial dysmorphology, malformation of CVS, Brain, Genito urinary system(Fetal alcohol syndrome) Basophilic stippling Leptin resistance, intertriginous dermatitis,Pickwickian syndrome, CV disease Ascites, decreased visceral protein compartment, 60 90% body weight Normal, hypoalbuminemia Decreased somatic protein Megaloblastic anemia, pernicious anemia, degeneration of spinal cord Bleeding diathesis Slow chilling Hypochromic, microcytic red blood cells Rapid freezing Ox Hunger, chipmunk facies, aspiration of gastric contents Nervous loss of apetite, osteoporosis, endocrine abnormalities Cramping of voluntary muscle Failure of CVS to compensate hypovolemia Rise in core temperature Italicized Additional information Gray Not an answer in Evals 8

GOODLUCK!

BATCH 2013 PATHOLOGY | 8TH EVALUATION

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