Endo & Repro pathology Flashcards
Lichen sclerosis
Thinning of the epidermis and fibrosis of the dermis
Presents as leukoplakia with parchment-like vulvar skin
Post-menopausal women
Increased risk for SCC (unlike lichen simplex chronicus
Lichen simplex chronicus
Hyperplasia of the vulvar squamous epithelium
Presents as leukoplakia with thick, leathery vulvar skin
Associated with chronic irritation and scratching
No increased risk of SCC (unlike lichen sclerosis)
Extramammary paget disease
Malignant epithelial cells in the epidermis of the vulva
Presents as erythematous pruiritic ulcerated vulvar skin
Carcinoma in situ, WITHOUT underlying carcinoma (unlike Paget disease of the nipple that is almost always associated with underlying carcinoma)
Paget cells are PAS+ (mucus), keratin+ (intermediate filament in epithelial cells), and S100- (marker of melanoma) vs melanoma which is PAS-, keratin-, S100+
Effects of diethylstilbestrol (DES)
DES is an estrogen-like compound that was used to treat pregnancy-related complications.
In female infants, it caused adenosis (persistence of columnar epithelium in upper vagina), clear cell adenocarcinoma, and abnormal shaped uteri and fallopian tubes
In mothers, it increased risk of breast carcinoma
No effect on male infants
Tumors with psammoma bodies
- Papillary carcinoma of the thyroid
- Meningioma
- Serous endometrial carcinoma
- Mesothelioma
- Serous cystadenocarcinoma (BRCA1)
Treatment of endometritis
Gentamicin + clindamycin +/- ampicillin
Brenner tumor
Benign ovarian tumor with bladder-like surface epithelium
Coffee-bean nuclei on H&E
Meigs syndrome
Triad of ovarian fibroma, ascites, and pleural effusion
Pulling sensation in the groin
Serous cystadenocarcinoma
Most common ovarian neoplasm. Frequently bilateral
Most commonly arises in postemenopausal women (cystadenomas are more common in premenopausal women)
BRCA1 mutation increases risk of serous carcinoma of the ovary and fallopian tube
Characterized by psammoma bodies
Pseudomyxoma peritonei
Intraperitoneal accumulation of mucinous material from ovarian or appendiceal tumor
Mature cystic teratoma (dermoid cyst)
Germ cell tumor that contains elements from all 3 germ layers; most common ovarian tumor in women 20-30 years old
Benign in women and children, malignant in men
Presents secondary to pain secondary to ovarian enlargement or torsion
hCG or AFP may be elevated
Struma ovarii - dermoid cyst that contains functional thyroid tissue
Immature teratoma
Malignant ovarian tumor; more aggressive than benign mature cystic teratoma (dermoid cyst)
Presence of immature tissue (fetal tissue, neuroectoderm) and somatic malignancy (SCC of skin) indicate malignant potential
Dysgerminoma
Most common malignant germ cell tumor
Composed of large cells with clear cytoplasm and central nuclei (resemble oocytes)
Equivalent to seminomas in males
Elevated LDH
Good prognosis, responds to radiotherapy
Yolk sac (endodermal sinus) tumor
Aggressive malignant ovarian/testicular neoplasm
Common in children (ovaries, testes, sacrococcygeal area)
Elevated AFP
Shiller-Duval bodies (glomerulus-like structures) characteristic
Choriocarcinoma
Malignant ovarian/testicular carcinoma consisting of cytotrophoblasts and syncytiotrophoblasts
Villi are ABSENT
Hemorrhagic tumor with early hematogenous spread to lungs (hemoptysis)
High beta-hCG (may lead to theca-lutein cysts, hyperthryoidism, gynecomastia)
Good response to chemo when it arises from gestational pathway (spontaneous abortion, normal pregnancy, hydratidiform mole); poor response to chemo when it arises from a spontaneous germ cell pathway
Krukenberg tumor
Metastatic mucinous signet cell adenocarcinonma that most commonly arises from diffuse subtype of gastric carcinoma
Differentiated from primary mucinous ovarian tumors by bilaterality of Krukenberg tumor
Preeclampsia
Usually arises in third trimester
Characterized by fibrinoid necrosis in vessels of placenta
HELLP - preeclampsia with thrombotic microangiopathy; characterized by Hemolysis, Elevated Liver enzymes, and Low Platelets
Tx of HTN in pregnancy: alpha-methyldopa, labetolol, hydralazine, nifedipine
Kallman syndrome
Form of hypogonadotropic hypogonadism caused by defective migration of GnRH cells and defective formation of olfactory bulb
Results in decreased synthesis of GnRH and anosomia
Lymphogranuloma venereum
Necrotizing granulomatous inflammation of the inguinal lymphatics and LNs caused by Chalmydia (serotypes L1-L3)
Heals with fibrosis
Serotypes of Chlamydia trachomatis
- A - C — cause trachoma: infection of the eyes, which can lead to blindness
- D - K — cause urethritis, PID, ectopic pregnancy, neonatal pneumonia, and neonatal conjunctivitis
- L1 - L3 — lymphogranuloma venereum
Bowen disease
In situ SCC of the penile shaft or scrotum
Presents as leukoplakia
Erythroplasia of Queyrat
In situ SCC of the glans fo the penis
Presents as erythroplakia
Bowenoid papulosis
In situ SCC that presents as multiple reddish penile papules
Unlike Bowen disease and Erythroplakia of Querat, it does not progress to invasive carcinoma
Orchitis
Inflammation of the testicle
Causes:
- Chlamydia (types D-K), N. gonorrhea - young adults; also cause prostatitis
- E. coli, Pseudomonas - older adults post-UTI; also causes prostatitis
- Mumps virus
- Autoimmune orchitis - granulomas involving seminiferous tubules
Risk factors for testicular germ cell tumors
- Cryptorchidism
- Klinefelter syndrome
Seminoma
Most common testicular tumor; resembles dysgerminoma
Large cells with clear cytoplasm and central nuclei (“fried egg” appearance) that forms a homogenous mass without hemorrhage or necrosis
Increased placental ALP, rarely may produce beta-hCG
Responds well to chemo
Embryonal carcinoma
Non-seminomatous testicular germ cell tumor
Painful hemorrhagic mass with necrosis. Immature primitive cells that may produce glands.
Aggressive with early hematongeous spread
Chemo may induce differentiation into another type of germ cell tumor (e.g. teratoma)
Increased beta-hCG or AFP may be seen
Leydig cell tumor
Benign sex cord-stromal tumor of the testicle
Produce androgen, causing precocious puberty in children or gynecomastia in adults
Characteristic Reinke crystals on histology
Sertoli cell tumor
Benign sex cord-stromal tumor of the testicle
Comprised of tubules, clinically silent
Most common testicular mass in males > 60 years old
Lymphoma (diffuse large B-cell type), often bilaterally
Treatment of prolactinoma
Dopamine agonists (bromocriptine, cabergoline)
Treatment of GH-producing adenoma
- Octreotide (somatostatin analog)
- Pegvisomant (GH receptor antagonist)
Nephrogenic diabetes insipidus (DI)
Collecting ducts respond poorly to ADH
Etiology: ADH receptor mutation, secondary to hypercalcemia, lithium, demeclocycline (ADH antagonist)
Findings: normal serum ADH, hyperosmotic volume contraction
No change in urine osmolarity after DDAVP (unlike central DI)
Tx: HCTZ, indomethacin, amiloride
Symptoms of hyperthryoidism
- Weight loss, heat intolerance, tachycardia
- Arrhythmia (A-fib)
- Staring gaze with lid lag
- Diarrhea with malabsorption
- Oligomenorrhea
- Bone resorption with hypercalcemia
- Hypocholesterolemia (increased LDL receptors)
- Hyperglcyemia
Symptoms of hypothyroidism
- Cretinism (MR, short stature, enlarged tongue, umbilical hernia)
- Myxedema (GAGs accumulate in skin and soft tissue due to increased TSH; result in deepening voice and large tongue)
- Weight gain, cold intolerance, bradycardia
- Oligomenorrhea
- Hypercholesterolemia (decreased LDL receptors)
- Constipation
Hashimoto thyroiditis
Autoimmune destruction of thyroid gland; associated with HLA-DR5
Antithyroglobulin and antithyroid peroxidase antibodies are signs of thyroid damage (do not mediate disease)
Chronic inflammation with germinal centers and Hurthle cells (eosinophilic metaplasia of cells that line follicles)
Increased risk for marginal zone B cell lymphoma
Subacute granulomatous (De Quervain) thyroiditis
Granulomatous thyroiditis following viral infection
Tender thyroid with transient hyperthyroidism
Rarely progresses to hypothyroidism
Riedel fibrosing thyroiditis
Hypothyroidism with a “hard as wood” nontender thyroid gland
Extensive fibrosis of thyroid gland; may extend to local structures (airway) but do not confuse with anaplastic carcinoma of the thyroid
Papillary carcinoma of the thyroid
Most common type of thyroid carcinoma
Risk factor: exposure to ionizing radiation in childhood
Increased risk with RET and BRAF mutations
Papillae lined by cells with clear “Orphan Annie eye” nuclei and nuclear grooves, and psammoma bodies
Often spreads to cervical LNs; excellent prognosis
Follicular carcinoma of the thyroid
Malignant proliferation of thyroid follicles surrounded by a fibrous capsule with invasion through the capsule (distinguishes follicular carcinoma from follicular adenoma)
Metastasis occurs hematogenously
Medullary carcinom of the thryoid
Malignant proliferation of parafollicular C cells (neuroendocrine cells that secrete calcitonin)
Biopsy reveals sheets of malignant cells in an amyloid stroma (consisting of calcitonin deposition)
Familial cases are often due to MEN 2A/2B (RET oncogene)
Symptoms of hypocalcemia
- Numbness and tingling (particularly circumoral)
- Tetany - may be elicited with filling of BP cuff (Trousseau sign; tap the “tricep”) or tapping on facial nerve (Chvostek sign; tap the “cheek”)
Diabetic nephropathy
Non-enzymatic glycosylation of arterioles leads to hyaline arteriosclerosis; involvement of renal arterioles leads to glomerulosclerosis
Preferential involvement of efferent arterioles leads to glomerular hyperfiltration injury that eventually progresses to necrotic syndrome; characterized by Kimmelstiel-Wilson nodules in glomeruli
Prevented by ACE inhibitors
Gastrinoma (Zollinger-Ellison syndrome)
Treatment-resistant peptic ulcers
Somatostatinoma
Achlorhydria (inhibition of gastrin)
Cholelithiasis with steatorrhea (inhibition of CCK)
VIPoma
Watery diarrhea
Hypokalemia
Achlorhydria
Thyroid storm
Stress-induced catecholamine surge in patients with hyperthyroidism
Presents with agitation, delirium, fever, diarrhea, coma, and tachyarrythmias
Tx (“3 P’s”): Propanolo, PTU, Prednisolone
Pseudohypoparathyroidism
Albright hereditary osteodystrophy
Autosomal dominant unresponsiveness of the kidney to PTH
Results in hypocalcemia, shortened 4th/5th digits, short stature
Carcinoid syndrome
Most common malignancy of the small intestine
Asymptomatic if tumor is limited to GI tract (5-HT undergoes first-pass metabolism in liver)
Presents with diarrhea, cutaneous flushing, asthmatic wheezing, and right-sided valvular disease
Increased 5-HIAA in urine and niacin deficiency (pellagra)
Tx: resection and octreotide
MEN 1 (Wermer syndrome)
Autosomal dominant
“Diamond”
- Pituitary tumor (prolactin or GH)
- Parathyroid tumors
- Pancreatic tumor (Z-E syndrome, insulinoma, VIPoma, glucagonoma)
Commonly presents with kidney stones and stomach ulcers
MEN 2A (Sipple syndrome)
Autosomal dominant
“Square”
- Medullary thyroid carcinomas
- Parathyroid hyperplasia
- Pheochromocytoma
Associated with RET gene mutation
MEN 2B
Autosomal dominant
“Triangle”
- Oral/intestinal ganglioneuromatosis (mucosal neuromas)
- Medullary thyroid carcinoma
- Pheochromacytomas
- Associated with marfanoid habitus
Associated with RET gene mutation
High-dose dexamethasone
- Suppresses ACTH production by pituitary adenoma
- Does NOT suppress ectopic ACTH production (e.g. small cell carcinoma of the lung)
Low-dose dexamethasone fails to suppress cortisol in all causes of Cushing syndrome (only suppresses cortisol in normal patients)
Pheochromocytomas
Tumor of chromaffin cells
Diagnosed by increased serum metanephrines (break-down product of epi) and increased 24-hour urine metanephrines and vanillylmandelic acid (break-down production of both epi and norepi)
Associated with MEN 2A/2B, von Hippel-Lindau disease, and NF type 1
Neuroblastoma
Most common tumor of the adrenal medulla in children (
May occur anywhere along the sympathetic chain
Commonly presents with abdominal distension and a firm, irregular mass that can cross the midline (vs. Wilms tumor, which is smooth and unilateral)
Increased homovanillic acid (breakdown product of dopamine) in the urine)
Bombesin+
Associated with overexpression of N-myc oncogene
Periductal mastitis
Inflammation fo the subareolar ducts
Usually seen in smokers (relative vitamina A deficiency results in squamous metaplasia of lactiferous ducts, producing blockage and inflammation)
Presents as subareolar mass with nipple retraction
Mammary duct ectasia
Inflammation and dilatation (ectasia) of subareolar ducts
Classically arises in multiparous postmenopausal women
Presents as periareolar mass with green-brown nipple discharge
Chronic inflammation with plasma cells seen on biopsy
Intraductal papilloma
Classically presents as bloody nipple discharge in premenopausal women
Fibrovascular projections lined by luminal (epithelial) and myoepithelial cells
Distinguished from papillary carcinoma by :age of onset (carcinoma more common in postmenopausal women) and presence of myoepithelial cells (absent in carcinoma)
Klinefelter syndrome
XXY
Presents with testicular atrophy (hypogonadism), eunuchoid body shape, tall long extremities, gynecomastia, and female hair distribution.
Dysgenesis of seminiferous tubules leads to decreased inhibin and increased FSH
Abnormal Leydig cell function leads to decreased tesosterone, increased LH, and increased estrogen
Increased risk of germ cell testicular cancer and breast cancer
Invasive ductal carcinoma
Most common type of invasive carcinoma in the breast
Duct-like structures in a desmoplastic stroma. Subtypes:
- Tubular carcinoma - well-differentiated tubules that lack myoepithelial cells; good prognosis
- Mucinous carcinoma - tumor cells floating in mucus pool; older women; good prognosis
- Medullary carcinoma - large high-grade cells growing in sheets; higher incidence in BRCA1 carriers; lymphocytic infiltrate; good prognosis
- Inflammatoy carcinoma - carcinoma in dermal lymphatics; mimics acute mastitis; poor prognosis
Lobular carcinoma in situ
Dyscohesive cells lacking E-cadherin adhesion protein
Often multifocal and bilateral
Low risk of progression to invasive carcinoma
Tx: tamoxifen
Invasive lobular carcinoma
Invasive carcinoma that characteristically grows in a single-file pattern; no duct formation due to lack of E-cadherin
May exhibit signet-ring morphology
