Normal Lab Values

Week 5 - Immunopathology

Suggested readings from
Robbins 8th ed.
pp. 183-258; 510-520

Pathology Cases for Week 5

Microbiology Cases for Week 5

 

Pathology Case Descriptions

CASE NUMBER 26
[ImageScope] [WebScope]

Clinical History: This 48-year-old female was admitted with a history of chills, fever, and pain in the right upper quadrant. In view of a clinical diagnosis of cholecystitis, cholangitis and cholecystitis, the gallbladder was resected.

Image Gallery:

(Summary of Gross Findings - click here)
The walls of the gallbladder were thickened. The mucosa of the gallbladder is intact. Yellow tan faceted gallstones are present in this gallbladder.
(Summary of Microscopic Findings - click here)
This gallbladder had an unexpected finding. The small arteries in the wall are involved in a necrotizing and inflammatory process which appears to be in all stages of development, resolution, and healing. The earliest change seen is an acute fibrinoid necrosis of the wall of the artery, which appears in the innermost third of the media, frequently involves the wall in an eccentric arrangement, and finally involves the entire thickness of the wall. Many of these arteries are markedly dilated with the formation of aneurysmal-like sacs. There is a marked exudation of inflammatory cells both within the wall of the artery and surrounding the artery. These cells are made up of eosinophils, neutrophils, histiocytes and lymphocytes. In some of the vessels, the process appears to be in a healing phase with the site of artery represented by fibrous scar surrounded by a chronic inflammatory exudate. Arterioles, capillaries, and veins are relatively spared in this necrotizing process.
(Review Normal Histology - click here)
UMich 194 liver, gall bladder H&E Webscope Imagescope

At the lowest power on the virtual microscope slide you will see a portion of the gall bladder wall nestled in an indentation of the liver tissue. Examine the wall of the gall bladder with your microscope. Extensive folds of the mucosa extend into the lumen. The mucosa consists of a tall, simple columnar epithelium and its underlying connective tissue (constituting a lamina propria). No submucosa is defined. The muscularis consists of scattered bundles of smooth muscle. Deep to the muscularis is an adventitia consisting of rather dense connective tissue that binds the gall bladder to the liver. Where the surface of the gall bladder faces the abdominal cavity there is a serosa.

26-1. The primary site of inflammation is in the:

  1. Veins
  2. Gallbladder lamina propria
  3. Gallbladder muscularis
  4. Arteries

ANSWER

 

 

26-2. The layers of the vessel wall affected are:

  1. Intima
  2. Muscularis
  3. Adventitia
  4. ALL of the above

ANSWER

 

 

26-1. What is the BEST diagnosis?

  1. Wegener granulomatosis
  2. Kawasaki disease
  3. Takayasu arteritis
  4. Polyarteritis nodosa

ANSWER

 

 

 

CASE NUMBER 121
[ImageScope] [WebScope]

Clinical History: A 59-year-old white female had rheumatoid arthritis over a number of years. Subcutaneous nodules were present over the extensor surfaces of the arms. One of these was surgically excised.

Image Gallery:

(Summary of Gross Findings - click here)
A photograph of the patient's elbow is shown. Sometimes persons with rheumatoid arthritis (RA) have rheumatoid nodules form in subcutaneous locations at pressure points, such as the elbow shown here. Rheumatoid nodules may also appear viscerally, such as on the pleura of the lung.
(Summary of Microscopic Findings - click here)
There are cellular areas with a stellate shape representing necrosis of collagen. At the periphery is a zone of cells with nuclei oriented perpendicular to the area of necrosis. These are histiocytes. The outer zone contains chronic inflammatory cells and fibrous tissue.
(Review of Normal Histology- click here)
Norm No. 15 [ImageScope] [WebScope]

Skin consists of keratinizing stratified squamous epithelium. The keratin layer is eosinophilic. Nuclei are not present. Beneath the keratin layer is a layer of flat epithelial cells with small pyknotic nuclei. Cells are regular and not crowded. These keratinocytes rest upon a layer of basal epithelium and a thin basement membrane. Beneath the epidermis is the dermis which consists of loose connective tissue. Within the dermis are sweat and sebaceous glands. Some slides contain hair follicles. There is no inflammation. The blood vessels are patent and do not contain thromboemboli.

 

121-1. Based on the clinical history and histological appearance, this is MOST likely an example of:

  1. Tuberculosis
  2. Necrobiosis lipoidicum diabeticorum
  3. Crohn’s disease
  4. Rheumatoid nodule
  5. Sarcoidosis

ANSWER

 

 

121-2. The images depict a distinctive histological pattern characterized by a central focus of necrotic collagen surrounded by epithelioid histiocytes, chronic inflammatory cells and fibrosis. This is BEST described as:

  1. Palisading necrosis
  2. Palisading granuloma
  3. Necrotizing granuloma
  4. Necrotizing fasciitis

ANSWER

 

 

 

CASE NUMBER 19
[ImageScope] [WebScope]

Clinical History: This 51-year-old male had tuberculosis for many years.  He developed some ankle edema, and was found to have an enlarged liver and 2+ proteinuria.

Image Gallery:

(Summary of Gross Findings - click here)
Both kidneys were large, each weighing 250 grams. This chronic renal disease may actually increase the size of the kidney. Pale deposits of amyloid are present in the cortex, most prominently at the upper center. The liver weighed 1900 grams and was firm with a waxy appearance. The heart (not shown) was also large, weighing 470 grams.
(Summary of Microscopic Findings - click here)
Kidney: The same type of hyaline pink material is present in the glomeruli, and is deposited between the endothelial cells and the basement membrane. In some places, it may be present in masses that encroach on the lumen of the capillary. The amyloid can also be recognized in the walls of some small arteries, and in a few places can be seen around the tubules in the interstitial tissue.

Liver: Most of the liver is replaced by homogenous, hyaline pink-staining amyloid which has been laid down between the sinusoids and the liver cells. This would stain with Congo red, or would be metachromatic if stained with crystal violet. The liver cords are replaced or compressed, and appear as widely separated thin cords of cuboidal cells. Bile plugs are present in the bile capillaries.
(Review of Normal Histology- click here)
Kidney:

Norm No. 2 [ImageScope] [WebScope]

The kidney excretes soluble waste from the body and controls electrolyte balance. It consists of the cortex and the medulla. Within the outer cortex, glomeruli with delicate capillary loops are seen.  The basement membrane is thin and without inflammation or thickening. Bowman’s capsule that surrounds the glomerulus is thin. The interstitium demonstrates no evidence of inflammation or fibrosis.  In the areas between the glomeruli, tubules and arterioles are seen. The tubules are intact.  The vessels exhibit no narrowing or wall thickening. The inner medulla of the kidney contains only tubules and blood vessels. Larger arteries and veins are located at the interface between cortex and medulla.

Liver:

Norm No. 3 [ImageScope] [WebScope]

The liver is the organ that metabolizes nutrients received from the digestive tract. These nutrients and processed by tissue hepatocytes which are large polygonal cells. The hepatocyes are separated by portal triads. The triads consist of an artery, a vein and a bile duct. The bile duct is lined by cuboidal epithelium. The artery has a muscular wall and a flat endothelial lining. The sinuses are well defined and contain a small amount of blood.

 

19-1. What is the BEST diagnosis?

  1. Nodular diabetic glomerulosclerosis
  2. Systemic lupus erythematosis
  3. Amyloidosis
  4. Henoch-Schonlein purpura
  5. Diffuse mesangial sclerosis

ANSWER

 

 

19-2. This condition may be associated with:

  1. Rheumatoid arthritis
  2. Bronchiectasis
  3. Chronic osteomyelitis
  4. Multiple myeloma
  5. ALL of the above

ANSWER

 

 

19-3. Deposition of which of the following may produce the same histological appearance?

  1. Transthyretin (pre-albumin)
  2. Lambda immunoglobulin light chains
  3. β2 microglobulin
  4. ALL of the above

ANSWER

 

 

 

CASE NUMBER 264
[ImageScope] [WebScope]

Clinical History: Clinical History: A 38 year old white female complained of a mass in the neck of several months duration. At the time of examination the thyroid was enlarged and somewhat nodular. She had no symptoms of hypothyroidism or hyperthyroidism.

Image Gallery:

(Summary of Gross Findings - click here)
At the time of surgery the entire thyroid was enlarged, with an estimated weight of 60 grams. The tissue was pale and lobulated. A subtotal thyroidectomy was performed. The excised tissue weighed 30 grams.
(Summary of Microscopic Findings - click here)
The architecture of the gland is destroyed. A few acini are present. These vary in size. There is abundant lymphoid tissue in which are germinal centers. There are collections of rather large cells which do not form acini.
(Review of Normal Histology- click here)
Norm No. 5 [ImageScope] [WebScope]

Thyroid tissue consists of variably-sized, colloid-filled follicles.  The colloid is eosinophilic and homogeneous. The glandular thyroid cells are cuboidal. The capsule is intact.

 

264-1. These images depict an example of :

  1. Riedel’s thyroiditis
  2. DeQuervain thyroiditis
  3. Subacute lymphocytic thyroiditis
  4. Hashimoto’s thyroiditis
  5. Fungal thyroiditis

ANSWER

 

 

264-2. Which of the following is NOT a typical feature of this disease?

  1. Granulomatous inflammation
  2. Lymphoid follicles with prominent germinal centers
  3. Thyroid epithelial cells feature abundant, eosinophilic cytoplasm (oncocytic change)
  4. Destruction of thyroid acini
  5. ALL of the above

ANSWER

 

 

264-3. Concerning Hashimoto's thyroiditis:

  1. Granulomatous inflammation is a characteristic feature
  2. May present with either thyrotoxicosis and hypothyroidism
  3. Is distinguished from subacute lymphocytic thyroiditis by the paucity of lymphocytes
  4. Idiopathic retroperitoneal fibrosis is a common complication

ANSWER

 

 

264-4. With regard to thyroiditis:

  1. The epithelial cells in Hashimoto thyroiditis may display ample, eosinophilic cytoplasm (Hurthle cells)
  2. The fibrous variant of Hashimoto thyroiditis features keloid-like collagenous bundles that extend outside the thyroid gland
  3. The principal manifestation of subacute lymphocytic (painless) thyroiditis is hypothyroidism
  4. Riedel’s thyroiditis has a viral etiology and is associated with retroperitoneal fibrosis
  5. DeQuervain’s thyroiditis is an autoimmune disease

ANSWER

 

CASE NUMBER 18
[ImageScope] [WebScope]

Clinical History: This 29-year-old male's illness began 10 weeks prior to death, with an episode of "flu". Two weeks later his urine became "smoky". He was found to have hematuria, albuminuria and elevated BUN (180 mg/dl). He died from a pulmonary embolus.

Image Gallery:

(Summary of Gross Findings - click here)
The kidneys were enlarged (230 gm each). The surface was granular and covered with pinpoint hemorrhages in the fresh state. The external surface with capsule removed is illustrated.
(Summary of Microscopic Findings - click here)
There is marked proliferation of epithelium of Bowman's capsule producing "crescents". In places fibrin strands are intermixed with the epithelial cells. Tubules are dilated and contain many red blood cells. There is marked interstitial edema and presence of numerous leukocytes. The presence of a large number of crescents is a bad prognostic sign.
(Review of Normal Histology- click here)
Norm No. 2 [ImageScope] [WebScope]

The kidney excretes soluble waste from the body and controls electrolyte balance. It consists of the cortex and the medulla. Within the outer cortex, glomeruli with delicate capillary loops are seen.  The basement membrane is thin and without inflammation or thickening. Bowman’s capsule that surrounds the glomerulus is thin. The interstitium demonstrates no evidence of inflammation or fibrosis.  In the areas between the glomeruli, tubules and arterioles are seen. The tubules are intact.  The vessels exhibit no narrowing or wall thickening. The inner medulla of the kidney contains only tubules and blood vessels. Larger arteries and veins are located at the interface between cortex and medulla.

 

18-1. The pathology shown may be seen in a condition characterized by pulmonary hemorrhage and renal failure due to cross-reacting antibodies against the lung and kidneys. What form of hypersensitivity reaction is demonstrated in such a disease?

  1. Type 1
  2. Type 2
  3. Type 3
  4. Type 4

ANSWER

 

 

 

CASE NUMBER 17
[ImageScope] [WebScope]

Clinical History: Four years before death the patient was seen in the hospital because of nausea and vomiting. He had hematuria, proteinuria, urinary casts, and a BUN of 50 mg/dl. A diagnosis of "chronic glomerulonephritis" was made. He did well for over 3 1/2 years, with elevated BUN of 50-60 mg/dl. His blood pressure was 150/90. A month before death his BUN  increased and he died of renal failure.

Image Gallery:

(Summary of Gross Findings - click here)
Both kidneys, distorted by multiple irregular broad scars, were small, each weighing about 60 grams (compared to a normal kidney, as shown in the center) and were pale and finely granular. The cortex in each was markedly thinned.
(Summary of Microscopic Findings - click here)
All of the 4 main constituents of the kidney (glomeruli, tubules, vessels, and interstitial tissue) are involved. Although all glomeruli are abnormal, they are not involved to the same degree; some are completely replaced by fibrous tissue, others are only partly scarred, and a few still contain patent capillary loops. The latter have increased mesangial and epithelial cells of Bowman's capsule. The tubules are dilated; some contain red blood cells, but most contain hyaline casts. The interstitial tissue is rather diffusely infiltrated with many lymphocytes and plasma cells. There is a moderate to marked degree of arteriosclerosis.
(Review Normal Histology - click here)
Norm No. 2 Kidney
[ImageScope] [WebScope]

The kidney excretes soluble waste from the body and controls electrolyte balance. It consists of the cortex and the medulla. Within the outer cortex, glomeruli with delicate capillary loops are seen.  The basement membrane is thin and without inflammation or thickening. Bowman’s capsule that surrounds the glomerulus is thin. The interstitium demonstrates no evidence of inflammation or fibrosis.  In the areas between the glomeruli, tubules and arterioles are seen. The tubules are intact.  The vessels exhibit no narrowing or wall thickening. The inner medulla of the kidney contains only tubules and blood vessels. Larger arteries and veins are located at the interface between cortex and medulla.

17-1. What may have caused this end-stage glomerular disease?

  1. Previous post streptococcal glomerulonephritis
  2. Rapidly Progressive glomerulonephritis (RPGN)
  3. Membranous glomerulonephritis
  4. Membranoproliferative glomerulonephritis
  5. IgA nephropathy
  6. Focal Segmental Glomerulonepritis (FSGN)
  7. No antecedent history of acute glomerulonephritis
  8. All of the above

ANSWER

 

Microbiology Case Descriptions

Micro Case 17

Clinical history: A 50-year-old resident of Phoenix, Arizona, has a cough that has persisted for 1 month.  On physical examination, his temperature is 38.1°C. A chest radiograph shows 3.5-cm opacity with central cavitation in the right apical region.  An open lung biopsy is performed to exclude cancer.

Image Gallery:

(Summary of Microscopic Findings - click here)
Microscopic examination of the biopsy specimen shows caseating granulomatous inflammation containing 60-um spherules filled with smaller, rounded structures.

 

m17-1. Which of the following organisms is MOST LIKELY to be responsible for these findings?

  1. Aspergillus fumigates
  2. Coccidioides immitis
  3. Histoplasma capsulatum
  4. Mycobacterium tuberculosis
  5. Pseudomonas aeruginosa

ANSWER

 

 

 

Micro Case 18

Clinical history: For the past 3 weeks, a 52-year-old man has had a chronic cough with a low-grade fever. On physical examination, his temperature is 37.4°C.  A chest radiograph shows bilateral, scattered, 0.3- to 2-cm nodules in the upper lobes and hilar adenopathy.  A fine needle aspirate of one of the nodules shows inflammation with mononuclear cells, including macrophages that, with PAS or silver stains, show intracellular, 2- to 5-um, rounded, yeast-like organisms.

Image Gallery:

(Summary of Gross Findings - click here)
This gross section of lung shows a laminated granuloma.
(Summary of Microscopic Findings - click here)
This silver stained tissue section shows histiocytes in lung tissue.

 

m18-1. Which of the following infectious diseases is MOST LIKELY to produce these findings?

  1. Coccidioidomycosis
  2. Candidiasis
  3. Cryptococcosis
  4. Histoplasmosis
  5. Blastomycosis

ANSWER

 

 

 

Micro Case 19

Clinical history: For the past month, a 68-year-old man has had painful oral abcesses, fever, and a cough productive of yellow sputum.  On physical examination, there is dullness to percussion at the left lung base. A chest radiograph shows areas of consolidation in the left lower lobe.  Despite antibiotic therapy, the course of the disease is complicated by abscess formation, and he dies.

Image Gallery:

(Summary of Gross Findings - click here)
Abcess observed on chest surface with purulent, granular discharge.
(Summary of Microscopic Findings - click here)
Tissue surrounding the abcess is contains nodules with basophilic cores surrounded by polymorphonuclear leukocytes.

 

m19-1. Based on these clinical findings, what is the BEST diagnosis AND the likely causative agent?

ANSWER

 

m19-2. In a separate case, a middle aged man presented to his physician with a persistent cough of two months following an extended overseas trip to visit relatives. He had also noted a 10 pound weight loss and night sweats. A sputum was sent to the microbiology laboratory for routine bacterial culture and AFB culture. Kinyoun stain of his sputum was positive. What is the likely causative agent?

  1. Mycobacterium tuberculosis
  2. Actinomyces spp
  3. Fusobacterium nucleatum
  4. Nocardia spp.

ANSWER

 

Micro Case 20

Clinical history: A 42 year old HIV positive man has had a fever and cough for the past month. On physical examination, his temperature is 37.5. On auscultation of the chest, decreased breath sounds are heard over the right posterior lung. A chest radiograph shows a large area of consolidation with a central air-fluid level involving the right middle lobe. A transbronchial biopsy specimen contains gram-positive filamentous organisms that are weakly acid fast.

Image Gallery:

(Summary of Lab & Microscopic Findings - click here)
Gram stain of a bronchoalveolar lavage of the right middle lobe shows gram positive rods. Modified acid fast stain shows partially acid fast bacilli.

 

m20-1. What is the most likely organism?

  1. Mycobacterium tuberculosis
  2. Actinomyces spp
  3. Fusobacterium nucleatum
  4. Nocardia spp.

ANSWER

 

m20-2. Nocardia species are:

  1. branching, gram negative bacilli
  2. partially acid fast, beaded gram positive bacilli
  3. acid fast, branching gram negative filaments
  4. partially acid fast, gram variable filaments

ANSWER

 

 

 

IMMUNOPATHOLOGY Review Items

Key Vocabulary Terms

acute cellular rejection complement-dependent reaction  immunologic tolerance
acute serum sickness contact dermatitis immunosuppressive therapy
acute vascular rejection CREST syndrome keratoconjunctivitis sicca
allergen discoid and butterfly rash  LE cell
amyloid drug induced lupus erythematosus lupus anticoagulant
anaphylaxis endotheliitis Mikulicz syndrome
anergy epithelioid macrophage opsonization
antibody erythroblastosis fetalis pemphigus vulgaris
antibody-dependent cell mediated cytotoxicity graft arteriosclerosis phagocytosis
antigen graft-versus-host disease post transplantation lymphoproliferative process
anti-nuclear antibodies (ANA) granuloma rheumatoid factor
antiphospholipid antibody syndrome hematoxylin body self tolerance 
Arthus reaction histamine sicca syndrome
atopy human leukocyte antigen (HLA) complex Sjogren syndrome
autoimmune hemolytic anemia humoral rejection T cell mediated cytotoxicity
autoimmunity hyperacute rejection transfusion reaction
cellular rejection  hypercoagulable state transthyretin
central and peripheral tolerance hypersensitivity reaction tubulitis
chronic transplant rejection immunity wire loop lesions

LEARNING OBJECTIVES

Absolutely critical information you must know to practice medicine is in bold font.
Important information that will be needed for routine patient care is in regular font.
Information about less common diseases that you may encounter in clinical practice and that will probably appear on examinations is in italics

  1. Compare and contrast the four types of immunologically mediated (hypersensitivity) disorders and give examples of each. Describe clinical features, antigens, mediators, cells and tissues involved

  2. Compare and contrast the following types of type II hypersensitivity reaction:
    • complement dependent
    • antibody dependent cell mediated cytotoxicity
    • antibody mediated cellular dysfunction

  3. Compare and contrast acute serum sickness and Arthus reaction.

  4. Compare and contrast delayed-type hypersensitivity and T cell-mediated cytotoxicity.

  5. Compare and contrast the following types of transplant rejection:
    • hyperacute rejection
    • acute rejection
    • chronic rejection

  6. Discuss bone marrow transplantation in terms of:
    • indications
    • acute and chronic graft vs. host disease
    • pathogenesis
    • clinical presentation
    • complications

  7. Compare and contrast renal, heart and liver transplants in terms of general morphology of hyperacute rejection, acute rejection and chronic rejection, and other complications.

  8. Discuss the following disorders:
    • systemic lupus erythematosus (SLE)
    • discoid lupus erythematosus (DLE)
    • drug-induced lupus erythematosis
    • Sjögren syndrome
    • systemic sclerosis (scleroderma)
    • CREST syndrome
    • dermatomyositis
    • polymyositis
    • rheumatoid arthritis (RA)
    • juvenile rheumatoid arthritis (JRA)
    • ankylosing spondylitis
    • Reiter syndrome
    • mixed connective tissue disease
    • polyarteritis nodosa.  

  9. Compare and contrast the five patterns (classes) of lupus nephritis, in terms of:
    • terminology
    • relative frequency
    • morphology (light, immunofluorescent, and electron microscopic)
    • clinical features
    • prognosis

  10. Correlate these patterns of immunofluorescent staining for antinuclear antibodies with the specific antibody represented by each, and disease(s) associated with each:
    • homogeneous (diffuse)
    • rim (peripheral)
    • speckled
    • nucleolar

  11. Match these autoantibodies with theautoimmune disease(s) with which it is associated:
    • antinuclear (ANA)
    • anti-SS-A (Ro) and anti-SS-B (La)
    • anti-Smith (Sm)
    • anti-Scl-70
    • anti-double-stranded DNA
    • anticentromere
    • antiphospholipid
    • anti-nuclear RNP
    • antihistone
    • anti-Jo-1

  12. Compare and contrast the following immune deficiency syndromes:
    • X-linked agammaglobulinemia of Bruton
    • common variable immunodeficiency       
    • DiGeorge syndrome (thymic hypoplasia).
    • severe combined immunodeficiency syndrome.
    • Wiskott-Aldrich syndrome
    • C2 deficiencies
    • deficiency of C1 inhibitor (hereditary angioedema)
    • chronic granulomatous disease
    • myeloperoxidase deficiency

  13. Discuss secondary immunodeficiency syndromes in terms of etiologies.

  14. Discuss acquired immunodeficiency syndrome (AIDS), in terms of:
    • definition and diagnostic criteria
    • laboratory testing
    • incidence
    • associated infections and neoplasms
    • epidemiology
    • morphology
    • risk factors
    • therapeutic approaches
    • etiology
    • complications and prognosis
    • pathogenesis
    • immunologic defects

 

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