15 g, 3-4 cm

(size of a walnut)

- prostate symmetrically enlarged from BPH can weigh 200 grams or more

What is the usual bacteria responsible for prostatitis?

E. coli infection

(chlamydia and gonorrhea also)

This enzyme converts testosterone to DHT in the prostatic stromal cells.

5 alpha reductase type 2

Other name for BPH

Benign prostatic hyperplasia

aka

Nodular hyperplasia

- not premalignant, does not lead to prostate cancer

Main mediator of hyperplastic growth of prostatic stromal and epithelial cells in BPH

DHT

dihydrotestosterone

- synthesized in the prostate from testosterone by the enzyme 5 alpha-reductase, type II.

- since enzyme is concentrated in stromal cells, stromal cells are main site for DHT synthesis

- DHT enlarges prostate by autocrine (on stromal cells) or paracrine (epithelial cells) action

- DHT works synergistically with estrogens

True or False:

Most prostatic hyperplastic nodules arise in the peripheral zone.

false

- they arise in the central and transitional zone --> can compress urethra

- peripheral zone contains epithelial cells; ADENOCARCINOMA develops here, near rectum

Chlamydia trachomatis

- a bacterial like organism not found in urine analysis

- not culturable

Which statement about PSA is false?

A: PSA levels are elevated in both prostatitis and prostate cancer.

B: PSA levels are proportional to tumor load.

C: Definitive diagnosis is made with PSA levels.

D: PSA is monitored after therapy to detect metastases.

C: Definitive diagnosis is made with PSA levels.

- Definitive diagnosis is made on tissue biopsy.

Which stage of prostate cancer would have symptoms of lower back pain refactory to analgesics and obstruction of urinary flow?

A: A/1

B: B/2

C: C/3

D: D/4

C & D

- Jewett-Whitmore A,B,C, etc.

- Gleason's 1 = well differentiated, circumscribed

5 = poorly differentiated, infiltrating

- carcinomas develop in epithelia; by time man has obstruction cancer is already at stage 3 or 4

- treatment at this point may include hormone therapy, i.e. orchiectomy (removal of testicals)

Axial skeleton

- bone pain may be the presenting complaint

True or False

Cervical cancer is a sexually transmitted disease?

True

- HPV 16 and 18 are carcinogens

Koilocytosis

- a hyperchromatic nucleus surrounded by a clear halo

Which statement about cervical cancer is false?

A: Peak incidence is at 30 years

B: Squamuous cell carcinoma is the usual type

C: It is often preceded by CIN

D: Definitive diagnosis relies on tissue biopsy

A: Peak incidence is at 30 years

- peak incidence of CIN is 30 years of age

- peak incidence of SCC is 40 to 45 years of age

The precancerous lesion of the prostate that can be considered analogous to carcinoma in situ

PIN

prostatic intraepithelial neoplasia

- These lesions consist of benign glands with intra-acinar proliferations of cells that demonstrate nuclear anaplasia.
- both high-grade PIN and cancer typically predominate in the peripheral zone

What is the lowest Gleason score for a prostate tumor?

the highest?

since Gleason score is obtained by adding two most dominant patterns of differentiation, 1 being well-differentiated and circumscribed and 5 being poorly diffentiated and infiltrating:

lowest = 1+1  --> 2

highest = 5+5 --> 10

The finding of osteoblastic metastases in bone is virtually diagnostic of this form of cancer in men

prostate cancer

What cell types are typical of cervical cancer?

Endometrial cancer?

Cervical cancer: squamous cell carcinoma

- typically occuring in transitional zone

Endometrial cancer: adenocarcinoma

- background of hyperestrinism

multiple, firm, estrogen-dependent, non-cancerous uterine tumors

Leiomyomas or "fibroids"

- does not evolve to leiomyosarcoma

- can compress bladder or rectum

- frequently asymptomatic, but can cause abnormal bleeding or impair fertility

Heterotopia of functional endometrial tissue outside the endomyometrium

Endometriosis

What organ involved in endometriosis produces "chocolate cysts"?

involvement of the ovaries results in large blood-filled cyst-like abnormalities.

functioning endometrium undergoes cyclic bleeding-

aged blood (hemosiderin) give them their reddish brown color.

True or False:

Endometriosis, leimyoma, and endometrial adenocarcinoma all respond to estrogen.

True

in endometriosis heterotopic tissue bleeds cyclically

leimoyomas depend on estrogen for their growth

(can regress after menopause)

endometrial cancers develop on background of hyperestrinism (obesity, HRT, anovulatory cycles)

Salpingitis

inflammation of the fallopian tubes

- almost always caused by bacterial infection

(chlamydia, gonorrhea, TB)

- almost always a component of pelvic inflammatory disease (PID)

- common cause of ectopic tubal pregnancy

Bilateral metastases of GI adenocarcinoma to the ovaries.

Krukenberg tumor

The most common cancer of the female genital tract in the US.

Endometrial carcinoma

- all adenomas come from hyperplasia

severe hyperplasia = high risk

- genetic mutations in DNA mismatch repair genes

and PTEN (tumor suppressor gene - Cowden's)

Which is most lethal in US?

A. Cervical Cancer

B. Uterine cancer

C. Ovarian cancer

C. Ovarian cancer

- pap smear has made cervical cancer much less lethal

- ovarian cancer very advanced by the time symptoms arise

Most ovarian tumors arise from this type of cell.

Most germ cell tumors are this type.

Most ovarian tumors are from surface (coelomic) epithelial cells (70-80% of all ovarian neoplasms).

Most ovarian tumors that are from germ cells are mature teratomas, aka dermoid cysts.

If a woman had an ovarian tumor that released estrogen, causing endometrial hyperplasia and cancer, what is the histogenic origin of this tumor?

She would have a thecal cell tumor,

from sex-cord-stromal cells.

True or False:

Secondary metastases to the ovaries represent the majority of ovarian cancers.

False.

Most ovarian cancers arise from coelomic (epithelial) cells, and are of the serous type.

Metastases to the ovaries represents only 5% of neoplasms (e.g. Krukenburg tumor).

Nulliparity is a risk factor for what female cancer(s)?

Ovarian cancer & Breast Cancer

- also family history

-mutations in BRCA genes 1 and 2 in familial type ovarian cancers

- p53 mutations in 50% of ovarian cancers

- HER2/NEU and K-ras mutations in 30% of ovarian

Where in the mouth would a dermoid cyst be found?

along the midline of the floor of the mouth

A young woman goes in for an abdominal x-ray. Her doctor incidentally sees calcifications in her ovaries, representing teeth. What does she have?

Benign (mature) cystic teratomas

aka dermoid cysts

- differentiation of totipotential germ cells into mature tissues representing all 3 germ cell layers:

endoderm, ectoderm, mesoderm

- epidermis-lined cysts can contain hair, sebaceous secretions, teeth, cartilage, and more!

Fibroadenoma

- common in women under 30

- freely movable, firm, discrete nodule

- may be estrogen-dependent for growth

After the upper outer quadrant (50%), where are breast tumors most likely to be found?

Central portion (20%)

- Upper inner and lower inner quadrants both 10%

What disease is caused by the extension of DCIS into the lactiferous ducts and contiguous skin of the nipple?

Paget's disease of the nipple

The ______ subtype of DCIS is characterized by  the toothpaste-like necrotic tissue that can be extruded from transected ducts with gentle pressure.

comedone

This type of breast cancer accounts for 80% of all non-invasive breast cancers and is commonly associated with mammographically detectable calcifications.

DCIS

ductal carcinoma in situ

The most common cause of hyperthyroidism

Grave's Disease

What autoimmune disorder is virtually pathognomonic with exophthalmos?

Grave's disease

- serum autoantibodies against TSH receptors-->

increase thyroid hormone production

Most common cause of hyperpituitarism

pituitary adenoma

- benign tumor of anterior pituitary

e.g. somatotroph adenomas --> excess GH

corticotroph adenomas --> excess ACTH & MSH

Most common cause of hypopituitarism

Null cell adenoma

- non-functioning mass, can compromise anterior pituitary, non-secretory, silent

postpartum necrosis of the anterior pituitary

Sheehan's syndrome

- overworking mammotrophs cause enlargement of pituitary and infarction --> hypopituitarism

What is Cretinism?

3 possible causes?

Cretinism is hypothyroidism in children

1. Agenesis of the thyroid gland

2. Failure of thryoid hormone synthesis due to severe dietary deficiency of iodine

3. Dietary goitrogens block hormone synthesis

- leads to mental and physical maldevelopment

A child ingesting too many goitrogen-rich foods like cabbage, brussel sprouts, and cauliflower, while not ingesting enough iodine, might run the risk of developing what disorder?

Cretinism

Most cases of adult hypothyroidism are caused by what disease?

Hashimoto thyroiditis

- struma lymphomatosum

- HLA-DR5 and -DR3

- strong female predilection

This thryoid disease is associated with human leukocyte antigen alleles HLA-DR3 and HLA-B8.

Graves disease

- the most common cause of hyperthyroidism

(Hashimoto thyroiditis also involves HLA DR3 and DR5)

This thyroid disease is associated with human leukocyte antigen alleles HLA-D3 and HLA-D5.

Hashimoto thyroiditis

- the most common cause of adult hypothyroidism

- autoimmune destruction of the thyroid gland -->

struma lymphomatosum

Graves disease

Accumulation of mucopolysaccharides in connective tissue is associated with what thyroid disease?

Myxedema in the hypothyroid adult

e.g. symptoms of "myxedema madness" and

myxedema heart resulting from mps accumulation

What altered gene might you expect to find in a child that had received ionizing radiation to his neck?

mutation of RET - a tyrosine kinase

- associated with thyroid malignancy,

especially Papillary carcinoma resulting from ionizing radiation

The most common neoplasm of the thyroid

Follicular adenoma

- benign, but usually removed surgically to exclude malignancy

- usually solitary and non-functional

- composed microscopically of fully differentiated thyroid follicles of varying size.

True or False:

The most common type of thyroid cancer has cells with "Little orphan Annie-eye nuclei".

True

- Papillary carcinoma is the most common type

&

has malignant follicular epithelial cells having hypochromatic, empty-looking nuclei

Which is not a characteristic of Medullary thyroid carcinoma?

A. The majority of cancers arise sporadically

B. 20% develop as part of MEN2A or 2B

C. Tumors arise from thyroid Chief cells

D. Calcitonin is used as a biochemical marker

E. Congo red is used to visualize tumor amyloid

C. Tumor is made up of Chief cells

- the tumor arises in thyroid C cells, aka parafollicular cells, which secrete calcitonin

Lingual Thyroid

• heterotopic thyroid tissue on the dorsum of the tongue
• may be only functional thyroid tissue for some people
• diagnosed using iodide isotopes and radionuclide scanning

Thyroglossal tract or duct cyst

• common cyst originating from embryogenic epithelial remnants of duct or tract
• fluctuant swelling in midline of neck below hyoid bone
• cyst line by strat. squamous or columnar epithelium, thyroid tissue may be present in cyst wall

3 distinct metabolic pathways that are involved in the pathogenesis of the long term complications associated with diabetes mellitus?

1. Nonenzymatic glycosylation

AGE accumulation & AGE receptor-signaling

2. Activation of Protein Kinase C

hyperglycemia --> DAG synthesis -->PKC activation --> VEGF & TGF beta

3. Intracellular Hyperglycemia with disturbances in polyol pathways

glucose-->aldose reductase-->sorbitol & fructose

Say whether each of the following pancreatic complications is more characteristic of Type 1 Diabetes or Type 2:

Amyloid replacement of islets (amyloidosis)

Leukocytic infiltration of the islets (insulitis)

Decrease in number and size of islets

Amyloidosis - Type 2

(congo red!)

Insulitis and Decrease in islet # and mass - Type 1

What is Diabetic Microangiopathy?

Of what other diabetic complications is it the underlying basis?

Diabetic microangiopathy is the thickening of basement membranes in both vascular and nonvascular structures.

- Type IV collagen visualized by PAS staining

Underlying basis for:

diabetic nephropathy

retinopathy

neuropathy

What type of renal complication, with its characteristic Kimmelstiel-Wilson lesion, is virtually pathognomonic for diabetes?

Nodular glomerulosclerosis

A glomerular lesion made distinctive by ball-like deposits of a laminated matrix situated in the periphery of the glomerulus. These nodules are PAS positive and usually contain trapped mesangial cells.

True or False?

Hyperglycemia and Hypoglycemia can both be found in both Type 1 and Type 2 diabetes.

True

Would you be more likely to find ketoacidosis leading to coma in Type 1 or Type 2 diabetes?

How about hyperosmolar nonketotic coma?

Ketoacidosis - Type 1

Hyperosmolar nonketotic coma - Type 2

Wickham striae

Hyperkeratotic scales appearing as lacy white lines over the purpley skin lesions of

Lichen Planus

Civatte body

Anucleate apoptotic basal cell found in the inflamed papillary dermis of Lichen Planus

aka Colloid body

Which non-cancerous skin disorder can sometimes mimic the appearance of melanoma and is associated with an activating mutation in Fibroblast Growth Factor receptor 3?

Sebbhoreic keratosis

- proliferation of basal epidermal cells

- usually seen in older people

- can develop anywhere on body

- slick or oily texture

- not at risk for malignant transformation

True or False?

Melanocytic Nevi develop from melanocytes.

False.

They develop from nevus cells

theque = a nest of nevus cells

Melanocytes are identical to nevus cells, except that melanocytes __________.

Melanocytes have dendrites.

Nevus cells do not.

Which skin disorder is indicated by Erythema migrans, aka Geographic tongue?

Erythema migrans is the oral lesion of Psoriasis

 Melanocytic nevi can appear in the mouth

Lichen Planus can also appear in the mouth as reticular type lesions

True or False:

Congenital nevus is considered premalignant for melanoma.

True

especially large ones, sometimes called "garment" or "bathing trunk" nevus

can lead to dermal metastases

Most common type of skin cancer?

Other major types & percentages?

Basal cell carcinoma (75%)

Squamous cell carcinoma (20%)

Melanoma (2-5%)

Which predisposing-to-skin cancer condition is thought to be an autoimmune reaction against melanocytes?

A. Albinism

B. Vitiligo

C. Xeroderma Pigmentosum

D. Hutchinson Freckle

B. Vitiligo

- loss of pigmentation in the skin

- bilateral symmetry

True or False:

Solar keratosis is considered a precursor lesion for melanoma.

False;

It is considered a precursor lesion for squamous cell carcinoma.

What type of Melanoma am I?

- Sun exposure is not a factor; I am found in Asians and Africans most commonly

- I appear on the soles of feet & palms & under the nails & on the gingiva and hard palate

- I have a long radial growth phase

Acral lentiginous melanoma

What type of skin cancer would you not expect to find in the oral cavity?

Basal cell carcinoma

- usually on middle third of face

- sun exposed areas of head & neck

Acute episodes of severe blistering sunburn as a child are important in developing this type of skin cancer.

Melanoma

- has the highest rate of death of any skin cancer

Chronic lifetime sun exposure is important in developing this type of skin cancer.

Basal cell carcinoma

odontogenic keratocyst

- part of the nevoid BCC syndrome (AD)

- destructive jaw lesions, associated with impacted teeth, but can reoccur

What cancer or disorder is associated with abnormalities in the following genes?

1. p16INK4A/CDNK2A

2. PTCH

3. RET

4. n-MYC

5. PRAD1

6. FGF3

1. p16INK4A/CDNK2A --> familial Melanoma syndrome --> Melanoma

2. PTCH --> nevoid BCC syndrome --> BCC

3. RET --> familial (MEN2B) and sporadic medullary thyroid carcinomas & papillary thyroid carcinoma

4. n-MYC --> neuroblastoma

5. PRAD1 --> parathyroid tumors

6. FGF3 --> Sebbhoreic keratosis

Oral mucosal neuromas are often the first manifestation of which endocrine disease?

MENs 2B

(Multiple Endocrine Neoplasia syndrome)

aka  Williams Syndrome

- AD inheritance

- RET mutation

- patients can go on to develop medullary thyroid carcinoma and pheochromocytoma

The measurement of _____ , secreted from medullary thyroid carcinomas, is used as an indicator for diagnosis and post-operative follow up.

calcitonin

- Like normal C cells, medullary carcinomas secrete calcitonin

cutaneous Squamous cell carcinoma

Most common primary malignant tumor of bone

Osteogenic Sarcoma

(Multiple myeloma also most common?)

- peak incidence 10-25 yrs old

- most common location close to the knee

- dense spindle-cell stroma

- bony spicules, cartilage, or fibrous tissue made

What do the bones look like in OI?

Thin cortex, thin trabeculae

multiple fracture sites

trabeculae markedly decreased

HLA DR4 is associated with which joint pathology?

Rheumatoid arthritis

- panus formation, destruction of articular cartlilage

Ewing Sarcoma

- peak ages 5-20

- metaphysis in long bones mainly affected

- fever, leukocytosis

- radiolucent destruction of cortex w/ extension into the soft tissues - "ONION SKIN" appearance

- PAS+ tumor cells

- small, round, blue cells

What is corpora amylacea?

In what organ is it found?

Corpora amylacea is the laminated, proteinaceous secretory material contained in benign prostate glands.

Found in Nodular Hyperplasia (BPH).

What are the 3 most common sites for endometriosis?

recto-vaginal septum & uterosacral ligaments

ovaries

fallopian tubes

*regurgitation through fallopian tubes most likely hypothesis to explain how endometrial tissue gets to remote sites in endometriosis

Most common alteration of the female breast

Fibrocystic changes, "Fibrocystic disease"

• usually both breasts, multifocal
• lumpiness +/- tenderness
• irreversible
• due to physiologic exposure to ovarian hormones

Blue dome cysts

Nonproliferative fibrocystic change of the female breast

- an unopened cyst can look brown or blue

- cyst filled with serous turbid fluid

Whereas infiltrating ductal carcinoma almost always presents as a clinically palpable mass,  DCIS rarely does.

How is DCIS detected clinically?

Calcifications on mammography