2. Marc Imhotep Cray, M.D.
Cancer Incidence and Leading Causes of
Cancer Death in Men and Women in U.S.
2
Cancers w highest incidence in
men:
Prostate cancer
Lung cancer
Colorectal cancer
Leading causes of cancer deaths in
men:
Lung cancer
Prostate cancer
Colorectal cancer
Cancers w highest incidence in
women:
Breast cancer
Lung cancer
Colorectal cancer
Leading causes of cancer deaths in
women:
Lung cancer
Breast cancer
Colorectal cancer
Learn more: Cancer Facts and Figures, 2020_American Cancer Society.pdf
Important Note: Incidence of lung cancer and colorectal cancer both exceed incidence of
prostate and breast cancer when data for men and women are combined.
3. Marc Imhotep Cray, M.D.
Ten cancers commonly encountered on Boards:
A Case-based Review (Hypertext opens to Video Edu.)
3
1. Gastric Cancer
2. Breast Cancer
3. Pancreatic Cancer
4. Lung Cancer
5. Prostate Cancer
6. Cervical Cancer
7. Brain Cancers
8. Thyroid Cancer
9. Colorectal Cancer
10.Endometrial Cancer
4. Marc Imhotep Cray, M.D.
Vignette#1
4
A 54-year-old Japanese American man presents to the clinic
complaining of a gnawing epigastric pain. Upon taking a complete
history, you learn that he has lost 20 pounds over the last 2 months
and has been vomiting after meals. The pain has not been relieved
by the use of over the-counter antacids. On physical examination,
you note supraclavicular lymph node swelling and darkened,
thickened skin in the flexural areas of the patient’s legs and arms.
You schedule the patient for an upper endoscopy with cytologic
brushings and biopsies of any suspicious lesions as you fear that this
patient may have a very serious condition.
What is the Diagnosis?
5. Marc Imhotep Cray, M.D.
Gastric Carcinoma
5
Etiology and Epidemiology: Risk factors include chronic gastritis, dietary
nitrosamines, and excessive sodium intake; More common in men > 50 years of
age and in patients with blood group A
Pathology:
Intestinal type: Gross: lesion with irregular necrotic base and heaped-up margins,
usually located in lesser curvature of antrum or prepyloric region
Microscopic: glandular formation of mucin-producing cells
Diffuse type: Gross: infiltrative process producing rigid stomach wall (linitis
plastica or leather bottle stomach); Microscopic: clusters of gastric-type mucous
cells (signet-ring cells) within gastric wall; Can see early, aggressive, local
metastasis to the lymph nodes and liver
Clinical Manifestations: Presents with anorexia, weight loss, vomiting, and
gnawing epigastric pain not relieved by antacids; Lab findings: Hypochromic
microcytic anemia
6. Marc Imhotep Cray, M.D.
Gastric Carcinoma cont.
6
Treatment: Surgical resection
Note:
Virchow node is involvement of left supraclavicular node by
metastasis of stomach or other GI cancer
Krukenberg tumor is bilateral metastasis of GI (usually stomach)
cancer to ovaries
• Histologically, tumor has abundant mucus and signet-ring cells
Acanthosis nigricans refers to hyperpigmentation and epidermal
thickening of flexural areas
• It is suggestive of a visceral malignancy, including cancer of
stomach, lung, breast, or uterus
7. 7
Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. Philadelphia: Saunders, 2015.
8. 8
Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. Philadelphia: Saunders, 2015.
9. 9
Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. Philadelphia: Saunders, 2015.
10. 10
Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. Philadelphia: Saunders, 2015.
11. 11
Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. Philadelphia: Saunders, 2015.
12. Marc Imhotep Cray, M.D.
Gastric Adenocarcinoma: Key Points
12
Presentation of gastric adenocarcinoma is very similar to that of
peptic ulcer disease and gastroesophageal reflux disease
From 60% to 90% of cases of distal gastric adenocarcinoma are
attributed to chronic Helicobacter pylori infection
An ulcerated gastric lesion should always be biopsied b/c as many
as 5% may harbor gastric cancer cells
Adenocarcinoma comprises almost all gastric cancers and can be
classified by gross or microscopic pathologic appearance
Adenocarcinoma may produce distinct lesions or may infiltrate the
stomach diffusely
13. Marc Imhotep Cray, M.D.
Vignette #2
13
A 50-year-old woman presents to your clinic after finding a mass on the upper
outer quadrant of her left breast. After taking a thorough history, you learn that
her mother died from breast cancer and her maternal aunt was also diagnosed
with breast cancer at an early age. The patient started her period at age 11, did
not bear any children, and has not been through menopause. On physical
examination, she is markedly obese and you notice retraction of the skin and the
nipple on her left breast. You locate the mass in question during your breast
examination and find that it is fixed, hard, and nontender. The mass was not
present on her last mammogram dating back 2 years. You also feel palpable
axillary lymph nodes. You schedule the patient for an immediate mammography
and needle biopsy to confirm your suspicions.
What is the Diagnosis?
14. Marc Imhotep Cray, M.D.
Breast Carcinoma
14
Etiology and Epidemiology:
Risk factors include:
Family history of first-degree
relative with breast cancer at
young age (highest risk),
Autosomal dominant
inheritance of mutations in
BRCA1 or BRCA2 gene,
female gender,
Increased age,
Early first menarche,
Delayed first pregnancy,
Nulliparity,
Late menopause,
Radiation exposure, and
exogenous estrogen use
15. Marc Imhotep Cray, M.D.
Breast Cancer Morphology
15
Most common location of tumors within breast is in upper
outer quadrant (50%), followed by central portion (20%)
About 4% of women with breast cancer have bilateral primary
tumors or sequential lesions in the same breast
Breast cancers are classified morphologically according to
whether they have penetrated the basement membrane
• Those that remain within this boundary are termed in situ
carcinomas, and
• those that have spread beyond it are designated invasive
carcinomas
16. Marc Imhotep Cray, M.D.
Breast Cancer Morphology cont.
16
In classification, above main forms of breast carcinoma are as follows:
A. Noninvasive
1. Ductal carcinoma in situ (DCIS)
2. Lobular carcinoma in situ (LCIS)
B. Invasive
1. Invasive ductal carcinoma (includes all carcinomas that are not of a special
type)-70% to 80%
2. Invasive lobular carcinoma- 10% to 15%
3. Carcinoma with medullary features-5%
4. Mucinous carcinoma (colloid carcinoma) -5%
5. Tubular carcinoma-5%
6. Other types
Adapted from: Kumar, V; Abbas AK (Eds.), Robbins Basic Pathology,
10th Ed. Philadelphia, Pa : Elsevier, 2018;742.
17. 17
Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. Philadelphia: Saunders, 2015.
18. 18
Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. Philadelphia: Saunders, 2015.
19. 19
Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. Philadelphia: Saunders, 2015.
20. Marc Imhotep Cray, M.D.
Breast Cancer: Key Points
20
Nontender, firm breast masses with poorly delineated margins
are concerning for invasive breast cancer
Other findings concerning for breast cancer include nipple
discharge, nipple scaling, breast asymmetry, nipple inversion,
peau d’orange, erythema, and warmth.
Most common cause of breast masses in young women is
fibroadenoma
BRCA1 and BRCA2 mutations predispose to development of
breast cancer and account for approximately 25% of familial
breast cancer syndromes
21. Marc Imhotep Cray, M.D.
Breast Cancer: Key Points (2)
21
BRCA1 mutations additionally confer increased risk for development
of ovarian cancer
Most breast cancers arise from the intermediate ducts and are
invasive (invasive ductal carcinoma)
Ductal carcinoma in situ (DCIS) is thought to progress to invasive
ductal carcinoma in most women
Lobular carcinoma in situ (LCIS) progresses to invasive lobular
carcinoma in some women but not at the same rate of DCIS
progression
Estrogen receptor/progesterone receptor (ER/PR) and HER2/neu
(ERBB2) are important biomarkers and may guide adjuvant therapy
for breast cancer following resection
22. Marc Imhotep Cray, M.D.
Vignette #3
22
A 78-year-old man presents with a 2-month history of epigastric pain.
He describes the pain as a vague pressure that occasionally radiates to
his back. It does not reliably occur before or after meals. He has lost
20 lb in the last 2 months, though he attributes this to his recent lack
of appetite. He has taken NSAIDs with no relief. The pain occasionally
subsides when he leans forward while sitting up. He smoked two
packs of cigarettes per day for 35 years but quit 2 years ago.
Examination is significant for scleral icterus and a nontender palpable
gallbladder.
What is the Diagnosis?
23. Marc Imhotep Cray, M.D.
Pancreatic carcinoma
23
Pancreatic carcinoma is likely
Pain is present in over 70% of cases of pancreatic carcinoma and
often radiates to the back
Weight loss is suggestive of underlying neoplasm but may also be
related to depressive symptoms often seen in pancreatic cancer
Scleral icterus indicates obstruction of biliary ductal system
Courvoisier’s sign describes the finding of a nontender palpable
gallbladder on abdominal examination and also indicates
obstruction of the biliary ductal system
Courvoisier’s sign is more commonly seen in obstruction by a
neoplasm, whereas scleral icterus results from obstruction by any
mechanism
Pancreatic carcinoma - causes, symptoms, diagnosis, treatment, pathology_Osmosis
24. Marc Imhotep Cray, M.D.
Pancreatic Ca Risk Factors
24
Acquired risk factors include cigarette smoking (note that this patient was a
smoker), industrial chemical exposure, type 2 diabetes mellitus, and obesity
Hereditary risk factors include a family history of pancreatic cancer (7-8% of
pancreatic cancer patients have a first-degree relative with pancreatic cancer,
versus 0.6% of control subjects) and a familial form of chronic pancreatitis
• The following familial cancer syndromes also confer an increased risk of
developing pancreatic cancer:
o Peutz-Jeghers syndrome
o Ataxia-telangiectasia
o Hereditary nonpolyposis colorectal cancer (HNPCC)
o Familial breast cancer (BRCA2-positive)
25. 25
Pancreatic Ca Tumor Location Impacts Symptoms
Location of tumor in pancreas affects types of
symptoms and how soon they might start to show
For example, jaundice symptoms may appear when
tumor obstructs the head of pancreas
If tumor is in body or tail of pancreas, pain and weight
loss might be more likely
• Pancreatic cancer in body or tail can also take longer to
present w Sx, allowing tumor more time to grow or
metastasize before it’s found
https://www.hopkinsmedicine.org/health/conditions-and-
diseases/pancreatic-cancer/pancreatic-cancer-symptoms
Where would a pancreatic mass most likely be located in order to
cause biliary obstruction?
Ans. Pancreatic head
Two thirds of pancreatic cancers are located in head of pancreas,
where they can easily obstruct the biliary ductal system
One third of pancreatic cancers occur in the body or tail
26. Marc Imhotep Cray, M.D.
Pancreatic Cancer Gene Mutations
26
The KRAS gene is activated by a point mutation in 80% to 90% of
pancreatic cancers cause a deactivation of protein product’s
guanosine triphosphatase activity as a result, protein is
constitutively active
Ras activates multiple other intracellular signaling pathways
The p16 gene (important in cell cycle control) is most frequently
inactivated tumor suppressor gene inactivated in 95% of
pancreatic cancers
Many other mutations also occur in pancreatic cancers
For example, all pancreatic cancers and 83% of colon cancers have at least
one mutational event in a TGF-β pathway
27. Marc Imhotep Cray, M.D.
Histologic types of pancreatic cancer
27
Pancreatic adenocarcinoma: >90%Neoplastic cells arise from
ductal cells of pancreas form ductules and may even secrete
mucin
Neuroendocrine tumors: <5% Arising from neuroendocrine cells
of pancreas tend to be less invasive and have a better prognosis
Cystic tumors: <5% These tumors may be benign or malignant
also less aggressive than adenocarcinoma
28. Marc Imhotep Cray, M.D.
Pancreatic Adenocarcinoma Tx & Px
28
Px is poor
Tumors located in body or tail have an even poorer prognosis than
those located in head b/c they often do not produce Sn & Sx until
they have invaded adjacent structures
Tx: Surgical resection offers a median survival time of 18 months
and a 5 year survival rate of approx. 5-20%
• When tumors are not resectable, median survival time is 4 to 8 months
• Only 10% to 15% of all tumors are resectable at presentation
29. Marc Imhotep Cray, M.D.
Vignette #3 cont’ed.
29
An abdominal computed tomography (CT) scan reveals a mass at the
head of the pancreas. The splenic vein is completely occluded by clot,
and there is invasion of the superior mesenteric artery. No metastases
are seen. The tumor is deemed unresectable, and he is offered
palliative care.
What serum cancer marker is likely to be elevated in this patient?
Ans. CA 19-9
However, CA 19-9 lacks sufficient sensitivity (50-75%) and specificity (approx.
85%) to be used in the screening of asymptomatic individuals
However, CA 19-9 may be followed postoperatively in order to assess disease
progression or regression
30. Marc Imhotep Cray, M.D.
Vignette #3 cont’ed.
30
The patient returns to the office 1 month later and is noted to have a random
glucose of 180 mg/dL. He also complains of pain in his right calf. On examination
of his leg, you note a superficial palpable cord that is tender. A fasting glucose
drawn 2 days later is 124 mg/dL.
What two processes have developed in this patient?
Glucose intolerance tends to develop after Dx of pancreatic Ca has been made
due to destruction of normal pancreatic beta cells and ducts by tumor
Peripheral venous thrombosis (superficial thrombophlebitis) has developed
Patients w cancer are at an increased risk for clotting and frequently
develop both deep and peripheral venous thromboses
When migratory peripheral venous thromboses are noted in a pt. w
pancreatic cancer, it is called Trousseau’s syndrome or Trousseau’s sign
NB: DVT and PE are most common thrombotic conditions in pts w cancer
34. Marc Imhotep Cray, M.D.
Pancreatic Cancer: Key Points
34
Pain is frequently present in pts. w pancreatic adenocarcinoma & may radiate to
back
• Painless jaundice is another important presentation for pancreatic adenocarcinoma
Courvoisier’s sign refers to a nontender distended gallbladder palpable on
examination
CA 19-9 levels are typically elevated in pancreatic adenocarcinoma
• Although not helpful for screening asymptomatic patients, they may be helpful in
diagnosing a patient suspected of having pancreatic cancer
• May also be helpful in following disease progression
KRAS and p16 are two common genetic mutations found in pancreatic
adenocarcinoma
Glucose intolerance and Trousseau’s syndrome are among the many
complications of pancreatic cancer
35. Marc Imhotep Cray, M.D.
Vignette #4_Part 1
35
A 63-year-old man presents to your office after noticing that his left eyelid is
droopy. Upon further questioning, he admits to some shortness of breath over
the past 2 months, but attributes that to his 40-year-long heavy smoking habit.
Physical examination reveals ptosis and miosis of the left eye and extremely dry
skin of the left face. A chest x-ray demonstrates an irregular mass in the apex of
his left lung. You admit the patient to the hospital for a biopsy of the mass, but
you fear that the prognosis is not good.
What is the Diagnosis?
36. Marc Imhotep Cray, M.D.
Bronchogenic Carcinoma
36
Etiology: Cigarette smoking (especially linked w squamous cell and small cell
carcinoma); air pollution; ionizing radiation; asbestos; nickel; chromium
exposure
Pathology:
Squamous cell: Central location; hilar mass with cavitation; keratinization
of squamous cells
Adenocarcinoma: Peripheral location; includes two forms: (1) Bronchial
derived: develops on scar site, glandular elements w mucin cells; (2)
Bronchioloalveolar: multiple mucinous nodules (which appear on CXR), tall
columnar epithelial cells, which line the alveolar walls
Small cell: Central location; small, round, basophilic cells with little
cytoplasm (oat cell is a neoplasm of neuroendocrine Kulchitsky cells)
Large cell: Peripheral location; large polygonal undifferentiated cells
(pleomorphic giant cells w leukocyte fragments in cytoplasm)
37. Marc Imhotep Cray, M.D.
Bronchogenic Ca cont’ed.
37
Pathology cont’ed.
Metastases of all types often occur to adrenals, brain, liver,
bone
Important Notes:
Metastases of other cancers to lung are more common than
primary lung cancer and may spread to lung hematogenously,
via lymphatics or through contiguous growth
Carcinoid tumor can also occur in the lung
38. Marc Imhotep Cray, M.D.
Vignette #4_Part 2
38
A 71-year-old man presents to your office because of water retention. He states
that he keeps himself well-hydrated, but he does not feel that his intake matches
his output. Pertinent past medical history includes shortness of breath and weight
loss of 15 pounds over the past 3 months. He has smoked 2 1/2 packs of cigarettes
per day for 50 years. Besides looking into possible causes of urinary obstruction
and other diagnoses, you decide to send the man for a chest x-ray, which reveals a
central coin lesion. Based on the patient’s history, you expect to see small, round
cells with scant cytoplasm on a biopsy of the mass.
What s the Diagnosis?
39. Marc Imhotep Cray, M.D.
Bronchogenic Ca cont’ed
39
Clinical Manifestations:
Hemoptysis; chest pain; dyspnea; cough; weight loss; pleural effusion
(usually bloody); hoarseness (from recurrent laryngeal nerve paralysis)
Pancoast tumor: apical lung tumor resulting in Horner syndrome (ptosis,
miosis, anhidrosis) owing to tumor involvement of cervical sympathetic
plexus
Superior vena cava syndrome: facial swelling and dilation of veins of head
and upper limbs from tumor compression of SVC
Cushing syndrome (caused by ACTH-like protein production), SIADH (caused
by ADH-like protein production), and Lambert-Eaton syndrome (myasthenia
gravis-like illness resulting from defect in acetylcholine release) are all seen
in small cell carcinoma
• Imaging: CXR demonstrates pneumonic coin lesion
• Lab findings: Hypercalcemia (caused by PTH-like protein production) seen in
squamous cell carcinoma
40. Marc Imhotep Cray, M.D.
Bronchogenic Ca cont’ed
40
Treatment and Prognosis:
Surgery, radiation, and chemotherapy for nonsmall cell
lung carcinoma; radiation and chemotherapy
for small cell carcinoma
Overall 5-year survival rate is 10%–15%
41. Bronchogenic carcinoma, gross
The large carcinoma ( ) in the upper lobe is
arising in a lung with centriacinar
emphysema, suggesting cigarette smoking as
the risk factor
There are patchy infiltrates in lower lobe
representing pneumonia, likely from central
airway obstruction by this large mass
There is inferior congestion, likely
exacerbated by heart failure
Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. Philadelphia: Saunders, 2015.
43. 43
Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. Philadelphia: Saunders, 2015.
44. 44
Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. Philadelphia: Saunders, 2015.
45. Marc Imhotep Cray, M.D.
Lung Cancer: Key Points
45
Acute bronchitis is the most common cause of hemoptysis
• However, hemoptysis is also concerning for lung cancer and tuberculosis
Most common presentations of lung cancer are:
• Asymptomatic pulmonary nodule
• Change in “smoker’s cough”
• Nonpurulent “pneumonia” in an adult
• Persistent upper respiratory infection
• Hemoptysis
• Hoarseness
• Sn & Sx of metastatic disease
• Sn & Sx of paraneoplastic syndrome
46. Marc Imhotep Cray, M.D.
Lung Cancer: Key Points cont’ed.
46
Approximately 90% of lung cancers occur in smokers
Four most common histologic types of primary lung cancer are
squamous cell carcinoma, adenocarcinoma, large cell carcinoma,
and small cell carcinoma
Small cell lung cancer (SCLC) and non–small cell lung cancer (NSCLC)
behave very differently and have markedly different prognoses
Lung cancer can produce symptoms by local tumor growth, regional
spread, or metastatic disease
47. Marc Imhotep Cray, M.D.
Vignette #6
47
An 81-year-old man presents to the clinic complaining of pain with
urination. On taking a complete history, you learn that he has had
difficulty in starting and stopping the stream of urine for the last 4
months and has recently been suffering from severe back pain. On
physical examination, you perform a digital rectal examination and
find a large palpable prostate nodule, which is firm and irregularly
shaped. You fear that laboratory tests will demonstrate an increased
total PSA with a decreased fraction of free PSA and may also
demonstrate an increase in serum alkaline phosphatase. You
immediately refer the patient to a urologist for prostatic biopsy.
What is the Diagnosis?
48. Marc Imhotep Cray, M.D.
Prostate Carcinoma
48
Epidemiology: Most common cancer among men and second leading cause of
cancer death in men; Occurs in men > 50 years of age
Pathology:
Gross: Irregular nodules arising from peripheral group of glands
(peripheral zone of posterior lobe is most common)
Microscopic: Adenocarcinoma with well-defined glands lined by cuboidal
cells with large nuclei and prominent, large nucleoli;
• May also be undifferentiated with cells growing in cords or sheets
• Often see invasion of vascular or lymphatic vessels of prostatic capsule
• In later stages, may progress to bony osteoblastic metastasis via
hematogenous spread
NB: The most common acquired mutations in prostatic carcinomas
create TPRSS2-ETS fusion genes or act to enhance P13K/AKT
signaling, which promotes tumor cell growth and survival
49. Marc Imhotep Cray, M.D.
Prostate Ca cont.
49
Clinical Manifestations: Frequently asymptomatic, but may present with dysuria,
increased urinary frequency or back pain (if metastasis to bone); most often
diagnosed on digital rectal examination with palpation of irregular, enlarged, firm
nodule with confirmation of diagnosis via prostatic biopsy
Lab findings:
Increased serum PSA and prostatic acid phosphatase (useful tumor markers for
disease progression),
Increased total PSA with decreased fraction of free PSA
(Contrastly, BPH has Increased total PSA w proportionate increase in fraction of free PSA)
Increased serum alkaline phosphatase (if osteoblastic metastasis)
50. 50
Prostate Ca cont.
Treatment and Prognosis:
Prostatectomy; radiotherapy; GnRH
analogues (leuprolide);
antiandrogens (eg, flutamide);
chemotherapy
Can have an indolent or aggressive
course as predicted by Gleason
system of grading, which is based on
differentiation of tumor
NB: PSA testing and digital rectal
examination should be offered
annually for screening purposes
beginning at age 50
53. 53
(A) Adenocarcinoma of the prostate demonstrating small glands crowded in between larger
benign glands. (B) Higher magnification shows several small malignant glands with enlarged
nuclei, prominent nucleoli, and dark cytoplasm, as compared with the larger, benign gland (top).
Kumar V and Abbas AK. Robbins and Cotran Basis Pathology, 10th Ed. Philadelphia: Saunders, 2018, Fig 18-14, Pg. 701.
55. Marc Imhotep Cray, M.D.
Adenocarcinoma of the prostate. Carcinomatous tissue is seen on posterior
aspect (lower left). Note the solid whiter tissue of cancer, in contrast with spongy
appearance of benign peripheral zone on contralateral side.
55
Kumar V and Abbas AK. Robbins and Cotran Basis Pathology, 10th Ed. Philadelphia: Saunders, 2018, Fig 18-13, Pg. 700.
57. 57
Prostatic cancer: Key Points
70% of prostatic tissue is in the peripheral zone 70% of prostate cancer cases arise in the
peripheral zone
Peripheral zone is the only area accessible via digital rectal examination
Most cases of prostate cancer are asymptomatic and detected by abnormal findings on
digital rectal examination or elevated prostate-specific antigen (PSA)
PSA can be elevated in prostate cancer, benign prostatic hyperplasia (BPH), or prostatitis
Only a small number of men who develop prostate cancer will die as a result of it
Screening with annual PSA levels may allow detection of prostate cancer at earlier stages
Prognosis of prostate cancer is determined by Gleason grade (2-10) and tumor staging
(TNM system)
Prostate cancer spreads by local extension and metastases to bone (especially axial
skeleton) and pelvic lymph nodes
58. Marc Imhotep Cray, M.D.
Vignette #5
58
A 42-year-old woman presents to the clinic complaining of postcoital bleeding and
vaginal discharge. She complains of a 3-month history of spotting in her
underwear after intercourse and an odorous vaginal discharge that is not
purulent. Her social history is significant for past practice of prostitution and her
past medical history is significant for several STDs that were appropriately treated.
She has not had a routine PAP smear in over 10 years. After a PAP smear reveals
abnormal cells, you perform a cervical biopsy, worrying that you may find invasive
malignant cells in the cervix and adjacent koilocytosis. You fear that the patient
will need to undergo a hysterectomy with possible adjunct radiation therapy if
your suspected diagnosis is confirmed.
What is the Diagnosis?
59. Marc Imhotep Cray, M.D.
Dysplasia, Carcinoma in Situ, and Squamous
Cell Carcinoma of the Cervix
59
Etiology and Epidemiology: Associated with human papilloma virus (HPV) types
16, 18, 31, and 33, early age of first intercourse and multiple sexual partners
Occurs most commonly between the ages of 30 and 45
Pathology: Cervical dysplasia: Involves squamocolumnar junction; characterized
by cells with hyperchromatic nuclei, irregular nuclear contours, and scant
cytoplasm; epithelial growth begins at basal layer extending outward; classified as
Cervical Intraepithelial Neoplasia (CIN) Subtypes Grades I-III (or Squamous
Intraepithelial Lesions Low-grade to High-grade )
CIN I (LSIL) is characterized by atypical undifferentiated cells only in lower third
of epithelium, whereas
CIN II (HSIL) superficial layer of cells still shows differentiation and koilocytosis
CIN III (HSIL) has atypia through > 2/3 thickness of epithelium, koilocytotic
change usually is absent
60. Marc Imhotep Cray, M.D.
Dysplasia, Carcinoma in Situ, and Squamous
Cell Carcinoma of the Cervix (2)
60
Pathology cont:
Cervical carcinoma in situ (CIS): Dysplastic cells extending through entire
epithelium, but without invasion of basement membrane
Invasive cervical carcinoma (ICC):
Gross: can be exophytic, ulcerating, or infiltrating mass
Microscopic: usually squamous cell carcinoma with large cells and keratinization;
can be adenocarcinoma or undifferentiated carcinoma; arises from preexisting
CIN at squamocolumnar junction; non-neoplastic epithelial cells often
demonstrate koilocytosis (assoc. w. HPV infection)
Koilocytes, also known as halo cells, are a type of epithelial cell that develops
following a human papillomavirus (HPV) infection; They are structurally different
from other epithelial cells, in that, their nuclei are an irregular size, shape, or color
61. Marc Imhotep Cray, M.D.
Natural History of Squamous Intraepithelial
Lesions (SILs)
61
Lesion Regress Persist Progress
LSIL (CIN I) 60% 30% 10% (to HSIL)
HSIL (CINII,III) 30% 60% 10% (to carcinoma)*
*Progression within 10 years. LSIL, Low-grade SIL; HSIL, high-grade SIL
Redrawn after Kumar V and Abbas AK. Robbins and Cotran Basis Pathology, 10th Ed. Philadelphia: Saunders, 2018, Fig. 19.1 , Pg. 718.
Remember:
Cervical Intraepithelial Neoplasia (CIN) Subtypes Grades I-III (or Squamous Intraepithelial Lesions
Low-grade to High-grade )
CIN I (LSIL) is characterized by atypical undifferentiated cells only in lower third of epithelium,
whereas,
CIN II (HSIL) superficial layer of cells still shows differentiation and koilocytosis
CIN III (HSIL) has atypia through > 2/3 thickness of epithelium, koilocytotic change usually is absent
62. 62
Three Stages of squamous intraepithelial lesions (SIL)
Spectrum of squamous intraepithelial lesions (SIL) with normal squamous epithelium for
comparison: LSIL with koilocytotic atypia; HSIL w progressive atypia in all layers of the
epithelium; and HSIL w diffuse atypia and loss of maturation (carcinoma in situ, far right image)
Kumar V and Abbas AK. Robbins and Cotran Basis Pathology, 10th Ed. Philadelphia: Saunders, 2018, Fig. 19.6 , Pg. 719.
63. 63
Cytologic features of squamous intraepithelial
lesion (SIL) in a Papanicolaou Smear
Superficial squamous cells may stain either red or blue.
(A) Normal exfoliated superficial squamous epithelial cells. (B) Low-grade squamous intraepithelial lesion (LSIL).
(C and D) Both high-grade squamous intraepithelial lesions (HSILs). Note the reduction in cytoplasm and the increase in
the nucleus-to-cytoplasm ratio as the grade of the lesion increases. This observation reflects progressive loss of cellular
differentiation on surface of cervical lesions from which these cells are exfoliated
Kumar V and Abbas AK. Robbins and Cotran Basis Pathology, 10th Ed. Philadelphia: Saunders, 2018, Fig. 19.7 , Pg. 719.
64. Marc Imhotep Cray, M.D.
Dysplasia, Carcinoma in Situ, and Squamous Cell
Carcinoma of Cervix (3)
64
Clinical Manifestations: ICC: Irregular vaginal bleeding; postcoital
spotting; cervical ulceration; nonpurulent discharge; dysuria; invasive
disease can obstruct ureters and lead to renal failure
Treatment ICC: Hysterectomy; radiation therapy; prevention with
HPV vaccine
NB: Screening for cervical cancer with PAP smears should begin 3
years after intercourse and no later than age 21 and continue every
1–3 years until age 70
71. 71
Cervical Cancer: Key Points
Invasive cervical carcinoma typically manifests with abnormal vaginal bleeding or
postcoital spotting
Invasive cervical carcinoma most often occurs in the transformation zone of the cervix,
between original squamocolumnar junction and new squamocolumnar junction
Cervical carcinoma is a sexually transmitted disease, the etiologic agent of which is
human papillomavirus (HPV) (most frequently types 16 and 18); therefore, risk factors
are primarily related to sexual behaviors
Squamous cell carcinoma is the most frequent histologic type, occurring in 75% of cases
The Papanicolaou (Pap) smear has markedly reduced the incidence of invasive cervical
cancer in America as a result of its ability to screen for preinvasive lesions
72. Marc Imhotep Cray, M.D.
Vignette #6
72
A 59-year-old man presents to your office complaining of severe
headaches for the last week. He tells you that his headaches are often
associated with projectile vomiting. Physical examination reveals
bilateral papilledema and a CT scan of the head demonstrates an
irregular mass in the left cerebral hemisphere. When a CT-guided brain
biopsy demonstrates pseudopalisading malignant cells around areas of
necrosis, you realize that this patient’s prognosis is very poor.
What is the Diagnosis?
73. Marc Imhotep Cray, M.D.
Glioblastoma Multiforme
73
Etiology and Epidemiology: Assoc. w genetic mutations in several oncogenes
and tumor-suppressor genes, including TP53 (p53), RB gene (Learn them, First
AID 2020, Pg. 224.)
Most common primary brain neoplasm
Occurs most frequently betw. ages 40 and 60
Pathology (GBM is a Grade IV astrocytoma)
Gross: Variable, noncircumscribed lesion found in cerebral hemisphere
Microscopic: High-grade astrocytoma (arises from astrocytes); central areas
of necrosis and hemorrhage surrounded by multiple tumor cells, arranged in
a pseudopalisading fashion; high degree of anaplasia
74. Marc Imhotep Cray, M.D.
Glioblastoma Multiforme (2)
74
Clinical Manifestations: Seizures; headaches; nausea and vomiting; other signs of
increased intracranial pressure
Imaging: Mass effect, cerebral edema
Treatment and Prognosis:
Surgical resection w chemotherapy and radiation
Px is very poor w most pts. dying within a year of Dx
Note:
Low-grade astrocytomas, especially pilocytic astrocytomas, are benign, slow-
growing tumors occurring in cerebellum of children
On histology, Rosenthal fibers (eosinophilic, corkscrew fibers) are present
78. Marc Imhotep Cray, M.D.
Vignette #7
78
A 42-year-old woman presents to your office complaining of
headaches and vomiting over the past 4 months. Upon further
questioning, you learn that she also feels as if she trips more than
usual when she is walking and she has recently had more trouble
remembering things. A physical examination reveals bilateral
papilledema and reduced strength and hyperreflexia in both of her
legs. A CT scan reveals a parasagittal mass compressing the brain and
a CT-guided brain biopsy demonstrates a whorled pattern of tumor
cells with psammoma bodies. You tell the patient that she will most
likely need surgery to remove the tumor.
What is the Diagnosis?
79. Marc Imhotep Cray, M.D.
Meningioma
79
Etiology and Epidemiology: Benign, slow-growing tumor arising from
meningothelial cells of arachnoid; therefore external to brain
Multiple meningiomas can be present in pts w neurofibromatosis
type 2
Occurs most often in women after age 30
Pathology:
Gross: Usually round encapsulated mass w dural base; usually
occurs in convexities of cerebral hemispheres or parasagittal
region; usually does not infiltrate brain
Microscopic: Whorled pattern of tightly packed tumor cells;
psammoma bodies (laminated calcifications)
80. Marc Imhotep Cray, M.D.
Meningioma (2)
80
Clinical Manifestations: Sx are assoc. w compression of
underlying brain including seizures, headaches, N/V and other
signs of increased ICP
Treatment and Prognosis:
Surgical removal of tumor
Prognosis is good
Of Note: Meningiomas are second most common primary brain
tumors
84. Marc Imhotep Cray, M.D.
Vignette #8
84
A 49-year-old man presents to the emergency department with a
seizure. When he has been stabilized, he tells you that he has had
several severe headaches over the past couple of months. A CT scan
of his head reveals a large mass in the frontal lobe of his brain that
demonstrates areas of calcification. You admit him to the neurology
service and you suspect that he will need surgery to treat his
condition.
What is the Diagnosis?
85. Marc Imhotep Cray, M.D.
Oligodendroglioma
85
Etiology and Epidemiology: Relatively rare benign tumor derived from
oligodendrocytes; Commonly affects middle-aged people
Pathology:
Gross: Circumscribed, slow-growing gray mass often w cysts; usually occurs in white matter
of cerebral hemispheres (especially frontal lobe)
Microscopic: Sheets of uniform cells with round nuclei with clear cytoplasm (fried egg
appearance); often calcification is present; increased vascularity (“Chicken-wire” capillary
pattern)
Clinical Manifestations: Seizures; headaches; papilledema; other signs of
increased intracranial pressure (ICP)
Imaging: Calcification of tumor is detected on CT scan
Treatment and Prognosis: Surgical resection, followed by radiotherapy and
chemotherapy
Average survival time is 5–10 years after diagnosis
87. Marc Imhotep Cray, M.D.
Vignette #9
87
A 58-year-old woman presents to your clinic complaining of hearing
loss and a ringing in her left ear. The Weber and Rinne hearing tests
help you to determine that the hearing loss is caused by a sensory
disturbance and not a conduction deficit. You send the patient for an
MRI of her head, which reveals a mass at the left cerebellopontine
angle, impinging on cranial nerve VIII. You refer this patient to a
neurosurgeon for a biopsy and likely removal of the mass.
What is the Diagnosis?
88. Marc Imhotep Cray, M.D.
Schwannoma (an acoustic neuroma)
88
Etiology: Usually benign tumors arising from Schwann cells
Bilateral acoustic schwannomas are assoc. w
neurofibromatosis type 2
Pathology:
Gross: Encapsulated masses, often with cystic areas; usually occur
in cerebellopontine angle where it can compress cranial nerve
VIII (acoustic schwannoma)
Microscopic: Two growth patterns:
(1) Antoni A: tightly packed elongated cells with palisading nuclei
(2) Antoni B: loose arrangement of cells w microcysts
89. Marc Imhotep Cray, M.D.
Schwannoma (2)
89
Clinical Manifestations: Presents w Sx assoc. w compression of involved nerve
(cranial nerve VIII compression leads to pts. presenting w ipsilateral hearing
loss, tinnitus, and vertigo), seizures, headaches, N/V, and other signs of increased
ICP
Treatment and Prognosis:
Surgical resection of tumor
Prognosis is good
Note: Pineal tumors usually occur in young men betw. ages of 10 and 40
Presents w Parinaud syndrome (paralysis of upward gaze caused by pre-tectal and superior
colliculus damage,
Obstructive hydrocephalus [owing to compression of aqueduct of Sylvius], and
Endocrine abnormalities [owing to compression of hypothalamus])
92. Marc Imhotep Cray, M.D.
Vignette #10
92
A 6-year-old boy presents to his pediatrician’s office complaining of
frequent falls. Upon further questioning, you learn that the boy has
also been suffering from nausea and vomiting, which is usually
associated with headaches. During physical examination, you note
that the boy has an
ataxic gait and bilateral papilledema. You send the boy for a CT scan,
which reveals a mass in the cerebellum and dilated third and lateral
ventricles. You immediately refer the patient to a neurosurgeon.
What is the Diagnosis?
93. Marc Imhotep Cray, M.D.
Medulloblastoma
93
Etiology and Epidemiology: Highly malignant tumor arising in cerebellum;
assoc. w deletion on short arm of chr 17 (17p-)
Occurs mostly in children and accounts for 20% of all brain tumors in
children
Pathology
Gross: Gray, well-circumscribed tumor located at midline of cerebellum
Microscopic: Hypercellular sheets of anaplastic cells, demonstrating many
mitoses, scant cytoplasm, and hyperchromatic nuclei; cells are often
arranged in a rosette or perivascular pseudorosette formation (called
Homer Wright rosettes)
94. Marc Imhotep Cray, M.D.
Medulloblastoma (2)
94
Clinical Manifestations: Unsteady gait; obstructive hydrocephalus
(tumor may obstruct flow of CSF by compressing fourth ventricle);
seizures, headaches; N/V; other signs of increased ICP
Treatment and Prognosis:
Surgery w radiation and ChemoTx
With total excision and radiation, 5-year survival rate is 75%
98. Marc Imhotep Cray, M.D.
Vignette #11
98
An 8-year-old girl presents to your clinic complaining of blurry vision.
During physical examination, you note bilateral papilledema. A CT scan
of the head demonstrates a mass extending from the floor of the fourth
ventricle and dilated lateral and third ventricles. You suspect that a
biopsy of the mass would demonstrate cells with blepharoplasts in a
perivascular pseudorosette arrangement.
What is the Diagnosis?
99. Marc Imhotep Cray, M.D.
Ependymoma
99
Etiology and Epidemiology: Tumor arising from ependyma of ventricular system
Most commonly occur in children (usually in fourth ventricle), but can occur
in spinal cord of adults
Pathology:
Gross: Solid, papillary masses extending from floor of fourth ventricle
Microscopic: Uniform cells w round nuclei set in a fibrillary stroma and
arranged in a perivascular pseudorosette formation; tumor cells often have
blepharoplasts (rod near nucleus, which represents basal ciliary bodies)
100. Marc Imhotep Cray, M.D.
Ependymoma (2)
100
Clinical Manifestations: Obstructive hydrocephalus (tumor may obstruct flow of
CSF through compression of fourth ventricle); seizures; headaches; N/V; other
signs of increased ICP
Treatment and Prognosis: Surgical excision (difficult owing to proximity of
brainstem nuclei)
Px is poor w average survival time of 4 years
104. Marc Imhotep Cray, M.D.
Brain Cancers: Key Points
104
Meningiomas are the most common type of primary brain tumor, occurring in
27% of cases
Astrocytomas arise from astrocytes and are divided into four grades based on
histologic appearance. Of these grades, glioblastoma multiforme has the
worst prognosis
Glioblastoma multiforme is distinctive because of endothelial proliferation
and necrosis
• “Pseudopalisading” is often seen in glioblastoma multiforme
Uncal herniation syndrome results from hippocampal gyrus herniation
through the tentorial notch
• Herniation produces pressure on the posterior cerebral artery and brain stem
Herniation is caused by an increase in pressure in one intracranial
compartment
• This pressure increase is due not only to the presence of a space-occupying lesion but
also to significant edema in the parenchyma surrounding the lesion
105. Marc Imhotep Cray, M.D.
Thyroid Cancer
105
Malignant thyroid tumors cause 0.4% of all cancer deaths in US
Approximately 10,000 new cases are diagnosed each year
Mortality from thyroid cancer exceeds that from malignant
tumors of all other endocrine organs
Most cases of thyroid carcinoma occur between third and
seventh decades, but children can also be affected
Tumors occur in women 2.5 times more often than in men
106. Marc Imhotep Cray, M.D.
Thyroid Cancer (2) Investigations
106
Fine-needle biopsy (FNB or FNA [aspiration]) of thyroid nodules
makes a diagnosis in most cases
Prognosis is a function of morphology of tumor range from a
very indolent clinical course to a rapidly fatal disease
Radioscintigraphy of gland may help in assessing thyroid tumors
hyperfunctioning (“hot”) nodules are usually benign
“Cold” or nonfunctioning nodules, more frequently malignant, but may
also be benign (i.e., adenoma)
Clinical Correlation:
Fine-needle Aspiration of Thyroid Nodules
Fifteen percent of people have a detectable nodule in thyroid, either by palpation,
or by ultrasound imaging
Fine-needle aspiration (FNA) is a minimally invasive method to biopsy nodules and
screen for rare cases of carcinoma
107. Marc Imhotep Cray, M.D.
Thyroid Ca (4) Etiopathogenesis
107
Most important environmental factor is external
radiation
1. External radiation single most important environmental
factor assoc. w increased risk of developing thyroid
carcinoma esp. many years of exposure to of high dose
2. Iodine excess and TSH In regions where endemic goiter is
widespread, addition of iodine to diet has resulted in
increase in incidence of papillary cancer
108. Marc Imhotep Cray, M.D.
Thyroid Ca (5) Etiopathogenesis
108
3. Genetic basis familial clustering of thyroid cancer
has been observed especially in medullary
carcinoma
Molecular studies reveal thyroid Ca is a multistep
process:
i. Papillary thyroid carcinoma: mutation in RET gene
(overexpression) located on chromosome 10q is seen
in about 20% cases of papillary thyroid carcinoma
ii. Follicular thyroid carcinoma: About 50% cases of
follicular thyroid carcinoma have mutation in RAS
family of oncogenes includes H-RAS, N-RAS and
K-RAS
109. Marc Imhotep Cray, M.D.
Thyroid Ca (6) Etiopathogenesis
109
3. Genetic basis familial clustering cont.
iii. Medullary thyroid carcinoma: Medullary thyroid
carcinoma arises from parafollicular C-cells in thyroid
point mutation in RET-proto-oncogene is seen in both
familial (MEN2) as a well as sporadic cases of medullary
thyroid carcinoma
iv. Anaplastic thyroid carcinoma: This tumor either arises
from further dedifferentiation of differentiated papillary
or follicular thyroid Ca, or by inactivating point mutation
in p53 tumor suppressor gene or by mutation in gene
coding for β-catenin pathway
110. Marc Imhotep Cray, M.D.
Thyroid Cancer (7)
110
Major subtypes of thyroid cancer and their relative
frequencies are as follows:
Papillary carcinoma (more than 85% of cases)
Follicular carcinoma (5% to 15% of cases)
Medullary carcinoma (5% of cases)
Anaplastic (undifferentiated) carcinoma (<5% of cases)
Remember genetic markers:
Papillary thyroid carcinoma—RET gene
Follicular thyroid carcinoma—RAS family of oncogenes
Medullary thyroid carcinoma—RET-proto-oncogene
Anaplastic thyroid carcinoma—p53 tumor suppressor gene
111. Marc Imhotep Cray, M.D.
Papillary adenocarcinoma
111
Epidemiology
Most common endocrine cancer
Papillary carcinoma most common thyroid cancer (>75%)
More common in women than men (3:1)
o Usually occur in second and third decades
Main risk factor: assoc. w radiation exposure
Gross and microscopic findings
Usually multifocal
Papillary leafs intermixed w follicles
Psammoma bodies (35–45% of cases)
o Dystrophically calcified cancer cells
Empty-appearing nuclei
o Called Orphan Annie nuclei
Lymphatic invasion
Metastasize to cervical nodes, lung
Diagnose with FNA
112. Marc Imhotep Cray, M.D.
Papillary carcinoma cont.
112
Treatment
Subtotal thyroidectomy w sampling of cervical nodes
Followed in a few weeks by radiotherapy w 131I
Suppressive therapy w thyroid hormone
o Tumor is TSH dependent
Five-year survival rate > 95%
113. Marc Imhotep Cray, M.D. 113
Rubin R , Strayer DS Eds. Rubin’s Pathology: Clinicopathologic Foundations
of Medicine, 6th Ed. Baltimore: Lippincott Williams & Wilkins, 2012.
A. Cut surface of a surgically
resected thyroid displays a
circumscribed pale tan mass w
foci of cystic change
B. Branching papillae are lined by
neoplastic columnar
epithelium w clear nuclei
A psammoma body is
evident (arrow)
Papillary carcinoma of thyroid
114. Marc Imhotep Cray, M.D.
Follicular carcinoma
114
Epidemiology
Most common thyroid cancer presenting as a solitary cold
nodule
Female dominant cancer
Gross and microscopic findings
Invasion of capsule (distinguishing from follicular adenoma)
Neoplastic follicles invade blood vessels
Lymph node metastasis is uncommon
Metastasize to lung and bone (hematogenous)
Treatment similar to papillary cancer
Five-year survival rate >80% w treatment
115. Marc Imhotep Cray, M.D. 115
Rubin R , Strayer DS Eds. Rubin’s Pathology:
Clinicopathologic Foundations of Medicine, 6th Ed.
Baltimore: Lippincott Williams & Wilkins, 2012.
Evaluating integrity of capsule is
critical in distinguishing follicular
adenomas from follicular
carcinomas:
A. In follicular adenomas, a fibrous capsule,
usually thin but occasionally more prominent,
surrounds neoplastic follicles and no capsular
invasion is seen; compressed normal thyroid
parenchyma usually is present external to
capsule (top)
B. In follicular carcinomas demonstrate capsular
invasion that may be minimal, as in this case,
or widespread, with extension into local
structures (vasculature) of neck
Capsular invasion in follicular
carcinoma
116. Marc Imhotep Cray, M.D.
Medullary carcinoma
116
Epidemiology
Types
o Sporadic (80% of cases)
o Familial (20% of cases)
Familial type
o Associated w autosomal dominant MEN IIa/IIb (Sipple syndrome)
o MEN IIa syndrome
• Medullary carcinoma, hyperparathyroidism (HPTH), pheochromocytoma
o MEN IIb (III) syndrome
• Medullary carcinoma, mucosal neuromas (lips/tongue), pheochromocytoma
(See Endocrinology Tutorial 2_MEN Syndromes)
Familial type has a better prognosis than sporadic type
Ectopic hormones
o ACTH, which can produce Cushing syndrome
Male: female ratio is equal
118. Marc Imhotep Cray, M.D. 118
Pathogenesis
Tumors derive from parafollicular C cells
C cells synthesize calcitonin
o Tumor marker
o May produce hypocalcemia
o Converted into amyloid can be stained w Congo-red for histologic ID
C-cell hyperplasia is a precursor lesion
o Calcitonin levels increase w infusion of pentagastrin
Diagnosis
FNA
Serum calcitonin
Treatment
Total thyroidectomy
Genetic screening for familial cases
o Detection of mutation of RET proto-oncogene
o Thyroidectomy is performed if family member is a gene carrier
Medullary carcinoma cont.
119. Marc Imhotep Cray, M.D. 119
Medullary thyroid carcinoma. A. Coronal
section of a total thyroid resection shows
bilateral involvement by a firm, pale tumor.
B. The tumor features nests of polygonal
cells embedded in a collagenous framework.
The connective tissue septa contain
eosinophilic amyloid. C. A section stained
with Congo red and viewed under polarized
light demonstrates the pale green
birefringence of amyloid.
Rubin R , Strayer DS Eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine, 6th Ed. Baltimore:
Lippincott Williams & Wilkins, 2012.
120. Marc Imhotep Cray, M.D.
Anaplastic thyroid cancer
120
Epidemiology
Most often occurs in elderly women
Risk factors
o Multinodular goiter, history of follicular cancer
Rapidly aggressive and uniformly fatal
Treatment
o Palliative surgery often compresses trachea
o Irradiation or chemotherapy
Five-year survival rate is 5%
121. Marc Imhotep Cray, M.D. 121
Anaplastic carcinoma of thyroid
Rubin R , Strayer DS Eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine, 6th Ed. Baltimore: Lippincott Williams &
Wilkins, 2012.
A. tumor in transverse section partially surrounds the trachea and extends
into the adjacent soft tissue
B. tumor is composed of bizarre spindle and giant cells with polyploid
nuclei and numerous mitoses
122. Marc Imhotep Cray, M.D.
Thyroid Carcinoma Treatment
122
1° treatment for thyroid carcinoma is total
thyroidectomy w lymph node dissection depending
on tumor stage
Radioactive iodine is administered postoperatively to ablate
thyroid remnant
Anaplastic Ca irradiation or chemotherapy
Thyroglobulin (Tg) can then be used as a tumor
marker Tg is undetectable in absence of functioning
thyroid tissue Rising Tg following 131I ablation
indicates recurrence
123. Marc Imhotep Cray, M.D.
Thyroid Cancer: Key Points
123
Medullary thyroid cancers may occur as an isolated thyroid cancer or may be
part of multiple endocrine neoplasia type IIA (MEN IIA)
• Medullary thyroid cancers arise from C cells, which secrete calcitonin
Other types of thyroid cancer arise from follicular cells
Typical triad of MEN IIA is medullary thyroid carcinoma, pheochromocytoma,
and primary hyperparathyroidism
typical triad of MEN IIB is medullary thyroid carcinoma, pheochromocytoma,
and ganglioneuromatosis
Typical triad of MEN I is hyperparathyroidism, pancreatic islet cell tumor, and
pituitary tumor
Both MEN I and MEN II are inherited in an autosomal dominant fashion
124. Marc Imhotep Cray, M.D.
Vignette # 12
124
A 55-year-old white man presents to the clinic complaining of weakness
and fatigue. After taking a detailed history, you learn that he has been
suffering from intermittent rectal bleeding and loose stools and that he has
lost 15 pounds over the last 2 months. His family history is significant for
colon cancer. On physical examination, the patient has marked pallor and a
positive stool guaiac test. Laboratory tests reveal an iron deficiency anemia
and elevated CEA levels. You schedule a colonoscopy with biopsy for
pathologic confirmation of your presumptive diagnosis.
What is the Diagnosis?
125. Marc Imhotep Cray, M.D.
Colorectal Adenocarcinoma
125
Etiology and Epidemiology: Risk factors include adenomatous polyps,
long-standing ulcerative colitis, low-fiber diet, old age, positive family
history, hereditary nonpolyposis colorectal cancer (HNPCC), and familial
adenomatous polyposis (FAP)
Most commonly occurs between the ages of 60 and 80
Pathology:
Gross: Appearance varies from polypoid mass (proximal colon) to lesions
with ulcerated centers and irregular margins that circumscribe bowel
(distal colon)
Microscopic: Dysplastic columnar cells in glandular formation; may
produce mucin, some tumors may be anaplastic
126. Marc Imhotep Cray, M.D.
Colorectal Ca cont.
126
Clinical Manifestations: Can be asymptomatic; if symptomatic, presents with
pallor, weight loss, intermittent diarrhea, LLQ pain, or obstruction
Lab findings: Positive stool guaiac test; increased serum CEA; microcytic,
hypochromic anemia (iron deficiency anemia secondary to GI bleed)
Treatment: Surgical resection; chemotherapy (5-FU)
Note: Colorectal cancer is second leading cause of death owing to malignancy
U.S.
Preventive measures include screening all patients > 50 years of age with
colonoscopy every 10 years
Colorectal carcinoma - causes, symptoms, diagnosis, treatment, pathology-Osmosis
131. Marc Imhotep Cray, M.D.
Vignette #13
131
A 60-year-old woman presents to the clinic with postmenopausal
vaginal bleeding. After taking a complete history, you learn that she is
nulliparous and suffers from type 2 diabetes, which is well-controlled
with diet and insulin. On physical examination, the woman is obese
and has a blood pressure reading of 150/96. You decide to perform a
PAP smear as well as an endometrial biopsy. Based on the patient’s
presenting signs and medical history, you are worried that you might
find well-defined gland patterns lined by malignant stratified
columnar epithelial cells on endometrial biopsy.
What is the Diagnosis?
132. Marc Imhotep Cray, M.D.
Endometrial Carcinoma
132
Etiology and Epidemiology: Risk factors include unopposed estrogen
use, obesity, diabetes, HTN, nulliparity, and late menopause
Peak incidence is between 55 and 65 years of age
Endometrial carcinoma is most common gynecologic malignancy
Pathology: Typically preceded by endometrial hyperplasia
Gross: Localized polypoid tumor or diffuse tumor involving entire
endometrial surface
Microscopic: Adenocarcinoma characterized by well-defined gland
patterns lined by malignant stratified columnar epithelial cells; may
see some squamous cells
133. Marc Imhotep Cray, M.D.
Endometrial Ca. cont.
133
Clinical Manifestations: Presents with postmenopausal vaginal bleeding,
leading to early diagnosis; may cause obstruction of cervix with collection of pus
(pyometra) or blood (hematometra) presenting with lower abdominal pain
Treatment: Total hysterectomy and bilateral salpingo-oophorectomy; radiation
therapy
Important Note:
Endometrial hyperplasia is abnormal endometrial gland proliferation caused
by excess estrogen (eg, polycystic ovarian syndrome, estrogen-secreting
ovarian tumor, estrogen replacement therapy)
It manifests clinically with postmenopausal vaginal bleeding may lead to
endometrial cancer depending on degree of atypia
139. Marc Imhotep Cray, M.D.
Colorectal cancer: Key Points
139
Adenocarcinomas make up 98% of primary colon cancers.
Precursor lesion to adenocarcinoma is the colonic adenoma, of which the
villous type is the most carcinogenic and has the lowest incidence
About half of primary colon cancers occur distal to splenic flexure, though this
pattern has been changing in recent years
Genetics of colon cancer progression are some of the best-studied in oncology
• The tumor suppressor gene APC has to sustain two hits before the
sequence can continue The next step is usually a mutation of the proto-
oncogene KRAS The final step is inactivation of the ubiquitous p53
tumor suppressor gene