Repro path

Question 1

Here is a histologic sample of the cervix of a sexually active young woman. What is notable about the sample?

Answer 1

Cervical dysplasia:
Koilocytes from HPV infection: HPV has invaded basal cells. Crinkled, irregular nuclei with “normal maturation” of cells.

First AID:

• CIN 1, 2, or 3 (severe dysplasia, carcinoma in situ)
• Associated with HPV 16– E6–> inhibits p53 or HPV18–> E7–> inhibits Rb
• *Risk factors**: #1= multiple sexual partners
• Smoking, early sexual debut, HIV infection

Question 2

A woman presents to your office for a pap smear after not having one for 10 years. She noticed some bleeding and discomfort with intercourse. Upon exam, you find the following:

Answer 2

Invasive cervical carcinoma

Fully invasive carcinomas are exophytic/ ulcerating, and can be keratinizing or non-keratinizing.
- Can invade adjacent structures (parametrium, bladder, rectum) causing ureter obstruction (–> renal failure) and fistula formation. - Lymph spread to paracervical, hypogastric, external iliac lymph nodes

Question 3

Endometriosis

Answer 3

• *Endometriosis**:
• Non-neoplastic endometrial glands/stroma in abnL location outside utereus (may be due to retrograde menstrual flow)
• Ectopic endometrial tissue= Chocolate cysts (blood) in ovaries; red/blue punctate lesions on bladder mucosa; painful defecation during menstruation (in pouch of Douglas)
• NORMAL uterus size

Symptoms:

• Severe menstrual-related pain
• Painful intercourse, infertility

Tx: Oral contraceptives, NSAIDs, leuprolide (GnRH agonist), danazol (modified progestin)

• *Adenomyosis**= endometrium within myometrim–> enlarged uterus, menorrhagia, dysmenorrhea, pelvic pain
• Tx: hysterectomy

Question 4

A 60 year-old woman presents with post-menopausal bleeding. You perform an endometrial biopsy and find the following cell types:

Answer 4

Endometrial carcinoma:
FIRST AID:
Most common gynecological malignancy
- Peak at 55-65 years
- Presentation= vaginal bleeding (typically preceded by endometrial hyperplasia)
Risk factors:
- estrogen (w/o progestin): nulliparity, late menopause
- Obesity, diabetes, HTN
Increased myometrial invasion–> worse prognosis

Endometrial adenocarcinoma: 70% present at stage 1, surgery is sufficient for treatment. 5-year 96% survival with no metastases vs 66% with metastatic spread

Endometrial lining connects to vagina- presents early. ANY post-menopausal bleeding needs to be worked up (~10% associated with endometrial cancer)

Screening: transvaginal sonography; unable to complete meaningful endometrial stripe measurement. Not used for evaluating asymptomatic patients.

Diagnosis: dilation and curettage, endometrial biopsy, hysteroscopy (small camera inside uterus)

Treatment: surgery, radiation (whole pelvic or brachytheraphy= vaginal area), oral progesterone (high failure rate), chemotherapy (only in high-grade serous tumors like ovarian cancer)

Prognosis: 85% five-year survival

* Re-screen patients who have repeated bleeding within 3 months of first evaluation

Question 5

Leiomyoma

Answer 5

• *Leiomyoma**:
• Most common of all tumors in females
• Benign smooth muscle tumor(s) in uterus
• RARE malignant transformation (Leiomyosarcoma usually arises denovo and is highly aggressive)

Estrogen sensitive: increases with pregnancy, regresses with menopause

Symptoms:

• asymptomatic–> abnL uterine bleeding–> miscarriage
• Severe bleeding–> iron deficiency

Histo: whorled pattern of smooth m.

Question 6

An obese 28 year-old woman goes to a fertility clinic complaining of problems of conceiving after trying for 16 months. She states she has never had regular periods. She has acne and her fasting blood sugar is elevated. An ultrasound of her uterus and ultrasound is performed and the following image is taken. What is her diagnosis and treatment?

Answer 6

PCOS: polycystic ovarian syndrome. The patient has cytic ovaries, hirsutism (acne), is overweight, and shows some level of insulin resistance.

7% women affected by PCOS (leading cause of infertility): see cystic follicles, atresia, and persistant anovulation; hirsutism, acne, male-pattern alopecia, obesity

Labs:

• Increased LH, decreased FSH
• Increased Testosterone–> aromatization lead to increased estrogen levels

Treatment

• Weight reduction
• Low-dose OCPs (progesterone supplementation)
• Medoxyprogesterone–> decreased LH and androgenesis
• Spironolactone= blocks androgens (for acne, hirsutism)
• Clomiphene= SERM–> prevents estrogen from negatively inhibiting hypothalamus–> increased gonadotropin production (FSH, LH)–> ovulation

Question 7

A 26 year old woman comes to her physician complaining of bleeding in between periods. She ovulates every month (she has been watching her cycles as she prepares to get pregnant) but is concerned about this bleeding. Ultrasound reveals a cyst in one of her ovaries. What type of cyst is it?

Answer 7

Ovarian cyst: arises from surface epithelium (cortical inclusion) or from ovarian follicles (follicular/corpus luteum cysts). Asymptomatic, may see precocious puberty, menstrual dysfunction, rupture

• *1. Follicular cyst=** Unruptured graafian follicle. Most common ovarian mass in young women
• Hyperestrinism
• Endometrial hyperplasia

Corpus luteum cyst: delayed resolution of corpus luteum–> increased progesterone production–> menstrual irregularities

Theca lutein cysts (hyperreactio luteinalis): high gonadotropin levels–> multiple/bilateral cysts–> can rupture, leading to intraabdominal hemorrhage (associated with choriocarcinoma and moles)

* Can see virilization in 15% of affected women (elevated progesterone–> hirsutism)

Question 8

Below is a specimen recovered from an ovary. What type of tumor is this and what is the prognosis?

Answer 8

Dermoid cyst- mature teratoma

Ovarian germ cell teratoma: see somatic differentiation within germ cell. This is a mature teratoma (recovered from ovaries- therefore germ cells) and is much more likely to be benign. An immature teratoma is found in other tissues, is composed of embryonic tissue and is malignant (totipotent cells with 3 germ layers)

Though benign, these tumors grow other cell types within them that can transform into malignancy (ex. skin can lead to squamous cell carcinoma, or thyroid tissue can lead to papillary thyroid carcinoma)

Below: teratoma with adipose and thyroid papilary tissue

Question 9

Endometrioid cyst

Answer 9

Endometriosis within ovary–> cyst formation

• Varies with menses
• Chocolate cyst= filled with dark blood

Question 10

Ovarian germ cell tumors

Answer 10

Most common in adolescents

• *Dysgerminoma= malignant, rarer than male seminoma (hCG, LDH** producing)
• Sheets of uniform cells
• Associated with Turner’s syndrome

Choriocarcinoma= rare, malignancy of trophoblastic tissue

• NO chorionic villi
• Increased frequency of theca-leutein cytst
• Can derive from moles or post-partum in mother or babcy
• Elevated hCG- can mimic TSH–> hyperthyroidism
• Hematogenous spread to lungs

Yolk-sac (endodermal sinus) tumor= aggressive malignancy in ovaries, sacrococcygeal area of young children

• Yellow, friable solid masses
• 50% have Schiller-Duval bodies (resemble glomeruli)

Teratoma: 90% of ovarian germ cell tumors

• 2-3 germ cell layers
• Mature= dermoid, benign
• Immature (2 layers); aggressively malignant
• *Struma ovarii:** functional thyroid tissue–> hyperthyroidism

Question 11

Below is a sample from the ovary of a 60 year old woman with no children and a family history of breast cancer (sister at age 45, mother at 53). What is the abnormality below and what is the prognosis?

Answer 11

Serous cystadenocarcinoma

• 45% of ovarian tumors (other 45% benign cystadenoma)
• Malignant, bilateral
• Psammoma bodies (calcifications) on histology
• *Risk factors**: BRCA-1, BRCA-2, HNPCC
• Genetic predisposition: family history most important risk factor
• *Vs serous cystadenoma**: 45% of ovarian tumors; bilateral, fallopian-tube like simple ciliated columnar epithelium
• Benign
• Increased CA-125 (marker for ovarian cancer)

Question 12

Mucinous cystadenocarcinoma

Answer 12

• *Mucinous cystadenocarcinoma**:
• Malignant
• Pseudomyxoma peritonei= intraperitoneal accumulation of mucinous material from ovarian or appendiceal tumor

Histo: ceolomic/germinal epithelium dervied–> produces mucin

Question 13

Brenner tumor

Answer 13

• *Brenner tumor**:
• Benign, unilateral
• Resembles bladder: pale yellow-tan, encapsulated
• “Coffee bean” nuclei on H&E

Question 14

Below is a benign ovarian tumor removed from a 60 year old woman. She was diagnosed with this tumor due to increasing ascites/pleural effusion before it was removed but since removal her symptoms have resolved. What type of tumor is this and what was her diagnosis?

Answer 14

Benign fibroma= 75% of stromal tumors, associated with Meig’s syndrome= ovarian fibroma, ascites, hydrothorax (tumor causing ascites). Solid white tissue.

Benign thecoma (below)= similar to fibroma, may produce estrogens/androgens, causing systemic effects. Fatty yellow tissue.

Question 15

Below is a sample from an ovarian tumor removed from a post-menopausal woman. Before diagnosis, the woman presented with endometrial bleeding. What type of tumor is in the histologic sample below?

Answer 15

Granulosa cell tumor (post-menopausal adult form): presents with Call-Exner _body, an estrogen-producing cluster of cells with grooved nucle_i (causing endometrial thickening/hyperplasia).

Cystic, hemorrhagic tumor (see below)

Juvenile form seen in children and young women causing precocious puberty and hyperestrinism

Question 16

Krukenberg tumor

Answer 16

Krukenberg tumor: GI malignancy metastasizes to ovaries

–> mucin-sectreting signet cell adenocarcinoma

Question 17

Fibroadenoma

Answer 17

• *Fibroadenoma**: BENIGN
• Stromal tumor
• Small, mobile, firm mass with sharp edges
• MOST common tumor in women < 35 years
• Estrogen-sensitive: increased size, tenderness with pregnancy, menstruation
• NOT precursor to breast cancer

Question 18

Intraductal papilloma

Answer 18

• *Intraductal papilloma**:
• small tumor growing in lactiferous ducts
• Beneath areola
• BENIGN (v. small increased risk in carcinoma)

Symptoms: bloody or serous nipple discharge

Question 19

Phyllodes tumor

Answer 19

• *Phyllodes tumor**:
• Large bulky mass of conective tissue and cysts in stroma
• Leaf-like projections
• Most common in 6th decade
• BENIGN- but, some risk for malignancy

Question 20

Ductal carcinoma in Situ (DCIS)

Answer 20

• *Ductal carcinoma in situ**:
• Fills ductal lumen
• Ductal hyperplasia (major duct)
• No basement penetration (penetrates–> invasive ductal carcinoma= most common)

Question 21

Comedocarcinoma

Answer 21

• *Comedocarcinoma**:
• Ductal tumor
• Caseous necrosis (central necrosis with cancer cells around)
• Subtype of DCIS

Question 22

Invasive ductal carcinoma

Answer 22

• *Invasive ductal carcinoma**:
• Firm, fibrous, rock-hard mass with sharb margins
• Small, glandular duct-like cells
• “Stellate” morphology
• worst, most invasive, most common (76% of all breast cancers)

Question 23

Invasive lobular cancer

Answer 23

• *Invasive lobular cancer**:
• Orderly row of cells “Indian file”
• Bilateral with multiple lesions in same location

Question 24

Medullary breast cancer

Answer 24

• *Medullary breast cancer**:
• Fleshy, cellular, lymphocytic infiltrate
• Good prognosis

Question 25

INflammatory breast cancer

Answer 25

* *Inflammatory breast cancer**: - Dermal lymphatic invasion by breast carcinoma - **Peau d'orange** (Breast skin); neoplastic cells blocking lymphatic drainage - 50% survival at 5 years

Question 26

Paget's disease

Answer 26

**Paget's disease:** - Eczematous patches on nipple - Paget cell= large cell in epidermis with clear halo - Suggestive of underlying DCIS - also seen on **vulva**

Question 27

Sclerosing adenosis

Answer 27

* *Sclerosing adenosis**: - Increased acini and intralobular fibrosis (type of fibrocystic change) - associate with calcifications Fibrocystic disease= breast lumps from 25-menopause; pre-menstrual breast pain, multiple (bilateral) lesions) - Fluctuate in size - Does not indicate risk of carcinoma

Question 28

Epithelial hyperplasia of breast

Answer 28

* *Epithelial hyperplasia of breast**: - Increased epithelial cell layers in terminal duct lobule - Increased carcinoma risk with atypical cells

Question 29

A 72 year old African American man with increasing issues of urinary hesitancy and feeling of incomplete emptying is autopsied following a massive MI. His prostate is removed (below). Based on the gross appearance of his prostate and his symptoms, what was the pathology and how would he have been treated if his symptoms had progressed? What we he at risk for developing?

Answer 29

* *Benign prostatic hyperplasia:** 1. Mechanical Component - Glandular proliferation - Nodular enlargement of **periurethral (lateral and middle) lobes** 2. Dynamic Component - Baseline tonicity of smooth muscle (activated by alpha receptors) \*\* Prostate enlargement in BPH driven by androgens= dihydrotestosterone (DHT) Medical management - Alpha blockers - 5-alpha reductase inhibitors Symptoms: Obstructive symptoms: - Decreased force of stream - Feeling of incomplete emptying - Intermittency (double voiding) - Hesitancy (delay of onset of voiding) - Need to strain to empty bladder Irritative: - Frequency of urination - Urgency (strong desire to void) - Nocturia (waking to urinate) - Dysuria (pain during urination) - Hematuria (blood in urine) Diagnosis: 1. Assess symptoms: AUA symptom score: - 7 questions: Incomplete emptying, frequency, intermittency, urgency, weak stream, straining, nocturia - Each question has severity (1-5) - Mild= 0-7; moderate= 8-19; severe= 20-35 2. Labs: serum creatinine, PSA, urinalysis, urine culture 3. Check PVR (post-void residual) - Remaining volume after micturation - Transabdominal U/S or catheterization 4. Renal ultrasound: - Check for hydronephrosis, cortical thinning Treatment: 1. Observation 2. Medical management - Alpha blockers - 5-alpha reductase inhibitors 3. Surgery - Various methods of clearing bladder outlet (TURP, etc) Indications for surgery: - Refractory urinary retention (may require catheters. - Recurrent UTI - Renal Insufficiency - Bladder calculi - Recurrent gross hematuria from prostate Risks of surgery: - bleeding, bladder neck contracture - Retrograde ejaculation (30-97%)- usually indicator of treatment effectiveness - Tranurethral syndrome: absorption of hypotonic solution used in TURP procedure (hyponatremia)

Question 30

A 72 year old man comes to his physician for treatment of persistant lower back pain. An x-ray reveals lytic lesions in his L4 and L5 vertebrae. Serum levels indicate increased alkaline phosphatase and PSA. What is his diagnosis and where did the illness originate?

Answer 30

**Prostatic adenocarcinoma** **FIRST AID:** **- Posterior lobe** (peripheral zone) Diagnosis with PSA, needle core biopsies - PAP (prostatic acid phophatase) and PSA for monitoring **Symptoms**: osteoblastic metastases, increase in serum alk phos, PSA Multicentric on the peripheral zone Trans-rectal biopsy Grossly: irregular, yellow– white, indurated nodules Histo: Glands with conspicuous “nucleoli” that infiltrate the stroma • Lack architectural organization Immunohistochemical stain: used to prove that this biopsy is cancer - Benign glands will have basal cell layer - Basal cell layer markers are absent in cancer and present in benign glands and HGPIN - Alpha-methylacyl-CoA racemase (AMCAR) is present in prostate cancer and HGPIN - "PIN cocktail" - Use "Gleason grading system" to stage cancer

Question 31

A 24 year old man comes to the physician for a physical before starting school. On physical exam his right testicle is palpably enlarged. He said he hadn't noticed the enlargement and he's had no accompanying symptoms. Blood reveals elevated PLAP. Based on the gross specimen removed and his presentation, what would his diagnosis and treatment be?

Answer 31

* *Seminoma**: malignant painless testicular germ cell tumor - Affects males 25-35 - Increased PLAP= placental alkaline phosphatase - Radiosensitive= excellent prognosis - Mets LATE

Question 32

Answer 32

**Yolk sac (endodermal sinus) tumor** - Yellow, mucinous tumor - Analogous to ovarian yolk sac tumor: **Schiller-Duval** bodies= produce **AFP** (alpha fetoprotein), ressemble glomeruli

Question 33

Answer 33

**Choriocarcinoma of testes**: - Malignant--\> mets to lungs - Increased hCG--\> gynecomastia (b-hCG= LH analog, can also induce hyperthyroidism as it mimics TSH) Histo: disordered **synctiotrophoblastic** (beta-hCG), cytotrophoblastic elements

Question 34

Answer 34

**NSGCT: teratoma** **- Increased hCG and/or AFP in 50% cases** - More often malignant than in females Composed of tissues of the three germ cell layers: endoderm, mesoderm and ectoderm. • Second most common tumor in prepuberal testis presenting at 20 months. • Present in 50% of the mixed GCT • In adults, teratomas are malignant Histo: Tissue from all germ layers resembling normal adult tissue • May show malignant transformation (sarcoma, primitive neuroectodermal tumor, carcinomas) with worse prognosis • There are no useful markers other than histology and AFP to exclude yolk sac tumor

Question 35

Testicular Embryonal carcinoma

Answer 35

* *Testicular embryonal carcinoma**: - Malignant, painful, worse prognosis than seminoma - Glandular, papillary morphology - Rarely "pure" embryonal carcinoma - most commonly associated with increased hCG, normal AFP when pure (increased AFP when mixed

Question 36

Answer 36

**Testicular non-germ cell tumors** 10% are malignant Orchiectomy is curative * *Leydig cell tumor:** - crystalloids of Reinke - Androgen-producing--\> gynecomastia in adults, precocious puberty in boys - Testicular swelling • Can secrete androgens, estrogens, and corticosteroids: – Precocious physical - sexual development and feminization – Gynecomastia • Two distinct peaks, in childhood and adults 3rd - 6th decade • Grossly are well circumscribed, from 1 to 10 cm in diameter, yellow to brown, and larger tumors have fibrous trabeculae Histo: uniform cells with round nuclei and eosinophilic or vacuolated cytoplasm

Question 37

Answer 37

**Sertoli cell tumor= androblastoma** * Testicular mass \< age of 40 * Grossly are small (1 to 3 cm), solid, well-circumscribed, yellow–gray nodules * Large Cell Calcifying Sertoli Cell Tumor (LCCSCT) is a subtype associated with Peutz-Jeghers Syndrome and a component of Carney’s Complex Histo: columnar tumor cells arranged into tubules or cords in a fibrous trabecular framework reminiscent of seminiferous tubules

Question 38

Testicular lymphoma

Answer 38

Lymphoma mets to testes aggressive