Intro to repro pathology Flashcards
Why is the Reproductive system important?
- Survival of a species
- In production animals - continued
supply of product (meat, fibre, milk, etc.)
- Study of reproductive diseases – historically focused on cattle
- More recently diseases of companion animals studied in more detail
Portals of entry for pathogens?
•Ascending infection (through cervix)
–At oestrus (e.g. spermatozoa or venereal infection)
–Postpartum infections
–Equine placenta during pregnancy
•Haematogenous infection
–Mostly specific infections during pregnancy e.g. brucellosis
•Descending from ovary
–Rare
•Transneural infection
–Rare recrudescence of herpesvirus
Defense Mechanisms of repro tract?
•Innate immunity- sterile environment for the foetus but allowing entry of semen (antigenic):
–Physical barriers (e.g. cervix, positioning)
–Neutrophils, macrophages, complement, cytokines
•Adaptive immunity- response to pathogens but tolerate spermatozoa and foetus:
–Humoral immunity e.g. local and systemic antibodies
–Cellular immunity e.g. T-lymphocytes
What is the Influence of hormones on immunity?
- At oestrus - better drainage through open cervix
- In short:
- Oestrogen: E2 = good guy (regarding immunity only!)
- Progesterone: P4 = bad guy
- Disease resistance under influence of oestrogen e.g. upregulation of T- and B-lymphocytes under oestrogen in ruminants
- Uterus more susceptible to infection during progestational (progesterone influence) or luteal phase, including pregnancy
- Inflammation with epithelial and mucosal surface loss in the uterus results in decreased PGF2α production → no lysis of Corpus luteum → increased susceptibility to infection
Subdivisions of disorders of female genital tract?
Discuss ovarian disease?
Name the different types of ovarian disease
•Developmental anomalies
Agenesis, duplication, hypoplasia, vascular hamartoma
**•Cysts – relatively common** Periovarian (paraovarian) cysts Intraovarian cysts (within the ovary)
•Inflammation (Oophoritis)
•Miscellaneous diseases
Supernumerary follicles, adhesions between infundibulum and ovary, ovarian haematoma, atretic follicles
•Neoplasia
Germ cell neoplasms (dysgerminoma, teratoma)
Sex cord stromal neoplasms (granulosa cell tumour, thecoma)
Epithelial neoplasms (adenoma, carcinoma)
Which one is clinically significant?
Cystic lesions
Left – periovarian – usually cystic remnant of embryonic structures (paramesonephric ducts or mesonephric tubules or duct ), not associated with clinical signs
Right – intraovarian – numerous and common, many derived from Graafian follicles; others are epithelial cysts arising from surface epithelium or intraovarian rete ovarii (embryonic structures of mesonephric tubular origin). Can result in failure of ovulation
Discuss Follicular cysts/ cystic ovarian (Graafian) follicles?
How do they form?
What can the development possibly be due to?
Main consequence?
Failure of mature follicle to ovulate (COD –cystic ovarian degeneration)
–>2.5cm (cow); >1cm (sow)
–Persistence for >10 days (with or without functional CL)
Development possibly due to
–Abnormality in hypothalamo-hypophyseal-ovarian axis that causes deficiency of LH or of LH receptor in ovary
Main Consequence:
Failure of ovulation
Discuss a Anovulatory luteinised cyst (luteal cyst)?
- Develop from follicular cysts by delayed or insufficient release of LH (part of COD)
- Occur in cows and sows more often than in other species
- Luteinized cells line the cystic cavity
Discuss cystic corpora lutea?
- Corpus luteum with a cystic centre
- Normal ovulation but large cystic centre develops
- Ovulation papilla on surface
- No infertility
- Can be confused with luteal cysts
Discuss ovarian neoplasms?
What are the different types of them?
Germ cell neoplasm
- Dysgerminoma
- Teratoma
–will see hair and bone and other types of tissues
Gonadal stromal neoplasm
•Granulosa cell tumour –>
–Usually cystic or polycystic
–Can sometimes be more solid
- Thecoma
- Luteoma
Epithelial neoplasm
- Cystadenoma
- Cystadenocarcinoma (bottom pic)
–Common to affect both ovaries. Surface is irregular and covered with neoplastic masses
Secondary tumours
- Lymphomas
- Mammary carcinomas bitch
- Intestinal carcinomas cow
Discuss Germ cell neoplasms - rare?
Teratoma
- Totipotential germ cells (elements of 2-3 embryonic germ layers)
- Solid and cystic areas can include bone, hair, cartilage, fat, nervous tissue
- Mostly benign and well differentiated, however they can rarely be malignant
- Malignant teratomas are very rare, poorly differentiated
Discuss Sex cord-stromal tumours?
Granulosa-theca cell tumour:
- some produce steroids (androgen/ oestrogen/ inhibin)
- smooth surface with solid or cystic cut surface
- Mare, cow unilateral and benign (sometimes malignant in the bitch and often malignant in the queen)
Discuss Epithelial neoplasms?
(Cyst)adenoma and (cyst)adenocarcinoma (esp bitch)
Malignant forms:
- Often bilateral, multifocal and shaggy surface
- Transcoelomic spread possible (lateral extension and seeding on peritoneal surfaces)
- May result in ascites
Discuss Uterine Diseases?
What are the different groups?
•Inflammation
Endometritis (inflammation of the endometrium)
Metritis (inflammation of all layers of the uterine wall)
Pyometra (“pus present”)
•Non-inflammatory disorders
Torsion, rupture, prolapse, subinvolution of placental sites, pseudopregnancy, endometrial atrophy, endometrial polyps, endometrial hyperplasia, adenomyosis, mucometra
•Neoplasia
Uterine leiomyoma
Endometrial carcinoma
Lymphoma
Discuss non-inflammatory uterus disorders?
Non-inflammatory disorders
- Physical factors (e.g. torsion, rupture, prolapse)
- Endometrial growth disturbances (e.g. endometrial hyperplasia, mucometra/ hydrometra, pseudopregnancy)
What’s your diagnosis?
A)Cystic endometrial hypoplasia
B)Endometrial emphysema
C)Endometrial cyst
D)Cystic endometrial hyperplasia
E)Emphysematous cysts
Cystic endometrial hyperplasia
Uterus from a dog
Photo - endometrium is thickened, and there is cystic distention of endometrial gland lumens.
Increased progesterone in late oestrus or easy dioestrus and aberrant hormonal function may alter hormonal receptor expression –> may prime the uterus so that inflammation or irritation by bacteria or other substances stimulates the uterus to undergo hyperplasia
Discuss pyometra in bitches?
In bitch (queen less common)
–Infection independent of or supervening upon Cystic Endometrial Hyperplasia
–Mainly in older, entire nulliparous bitches
–Usually a few weeks (mostly 3-8) after oestrus under progesterone exposure (luteal phase)
–Bacterial infection of the endometrium (e.g. E.coli, Strep sp)
–Acute or chronic disease
–Can be life threatening (toxaemia, bacteraemia)
- Macroscopically there is distension of the cornua, the serosal surface of the uterus is darker, and the vessels are prominent.
- The nature of the uterine content is variable. In the more severe cases, usually those infected with E. coli
- and Proteus spp., the exudate is thick, opaque, red-brown, and with a characteristic fetid odour.
- In other cases, usually those infected with streptococci and staphylococci, the exudate is more typically suppurative.
How does a pyo appear macroscopically?
Macroscopically there is distension of the cornua, the serosal surface of the uterus is darker, and the vessels are prominent.
The nature of the uterine content is variable. In the more severe cases, usually those infected with E. coli
and Proteus spp., the exudate is thick, opaque, red-brown, and with a characteristic fetid odor.
In other cases, usually those infected with streptococci and staphylococci, the exudate is more typically suppurative.
Discuss pyometra in the cow?
In cow
–Mostly early postpartum (following endometritis/ metritis) or
–At various times after breeding (venereal infections)
–Persisting CL and high progesterone levels => increased susceptibility of the uterus to infection, functional closure of the cervix, inhibition of myometrial contractility
–Functional cervical closure but usually some discharge
–Rarely systemic signs
»Compared to the bitch
Discuss endometritis?
- Limited to uterine mucosa (endometrium)
- Post mating (seminal fluid) or Postpartum (dystocia)
- Mild cases usually self-limiting
- Severe cases can become chronic and fibrous
- Persistent CL in mare and cow in chronic endometritis (due to decreased PGF2alpha release)
- Contagious equine metritis -temporary infertility; clinical disease now rare
- Photo: The endometrium is swollen and red-brown and irregular/wavy. The uterus is open and we are seeing the endometrium inside.The endometrium is swollen and red-brown and irregular/wavy.
What’s your diagnosis?
A)Carcinoma
B)Lymphoma
C)Rhabdomyoma
D)Lipoma
E)Leiomyoma
F)Endometroma
A)Leiomyoma
We have a well demarcated mass in uterus
Most common tumours of the tubular genitalia of the bitch; smooth muscle in the wall of the uterus, cervix or vagina. Less common in other species
Characteristic gross features: solitary or multiple, not encapsulated but well demarcated, form, light tan to white and easily shelled out
Discuss Uterine adenocarcinoma
(epithelial neoplasia with glandular pattern)?
- Mainly in cow (has to be considered EBL suspect and notified - uterus one of tetrad of affected organs!)
- Metastases to regional lymph nodes, lungs and seeding in peritoneum
- Most common spontaneous tumour in rabbits!
Adenocarcinomas:
- On gross examination, the tumors are nodular, can be multicentric masses that often involve both uterine horns.
- On the cut surface, masses are firm, red to cream and may have paler areas of central necrosis.
- Typical microscopic features are the formation of acinar and tubular structures by the neoplastic cells. There may be also a large amount of fibrous tissue (which is part of what is called a scirrhous reaction). Metastases occur to the regional (medial iliac) lymph nodes and lungs, and they can seed the serosal surfaces of the abdomen.
Discuss Vagina/ vulval disorders?
Vulvar swelling (tumefaction)
Exposure to endogenous or exogenous estrogen
(ovarian cysts, estrogen-producing tumours, mycotoxins)
Inflammation
Granular vulvitis, infectious pustular vulvovaginitis of cattle (IPV), necrotic vaginitis and vulvitis, dourine
Neoplasias common here:
Leiomyoma, leiomyosarcoma
Squamous cell carcinoma
Canine transmisible venereal tumour
Fibropapilloma of the vulva
Transmissible genital papilloma of the pig
Discuss Neoplasia of Vagina/ Penis?
Canine transmissible venereal tumour
- Rare in the UK, but common in some other countries
- TVT cells have 59 chromosomes instead of normal 78 in dogs
- Transmission by transfer of neoplastic cells during coitus (xenotransplantation)
- Histo: large, round neoplastic cells with occasional large bizarre nuclei
- Vincristine responsive
- Metastases in dogs with poor health
Discuss Fibropapilloma (BPV-1)?
- Common tumour of the bovine vulvar and affects young animals primarily
- Single or multiple warty masses
- Macroscopically, there are single or multiple warty masses that have a papillary epithelial covering and a fibrous core. Surface ulceration is often extensive.
Discuss Squamous Cell Carcinomas?
- Mostly in stallions and geldings
- Associated with Equine Papillomavirus-2
- Frequent ulceration
- Recurrence if incomplete removal
- Low-grade malignancy usually
- Keratin pearl formation
- Histologically – polygonal, squamous cell like cells and have with formation of keratin pearls – typical histological feature
Discuss disorders of sexual development?
Normal sexual development
Levels at which sex can be defined:
- Genetic/ Chromosomal (xx/ xy) - sex chromosome type is established at conception
- Gonadal (testis/ ovary) - established early in development
- Phenotypic - type and arrangement of tubular genitalia and external genitalia established after the gonadal type is set
→ Disorders of sexual development (DSD) due to genetic/ chromosomal abnormalities or inappropriate hormone exposure during development
What are the 3 major categories of disorders of sexual development?
- An abnormal or missing sex chromosome
- A normal female karyotype
- A normal male karyotype
Sex chromosome DSD
Abnormal number and/or mixture of sex chromosomes, including XXY (Klinefelter syndrome), X_ (Turner syndrome), and XX/XY (chimerism).
XY DSD - disorders of testicular development, disorders of androgen synthesis or action
XX DSD - disorders of ovarian development, androgen excess, or miscellaneous disorders
(Note: SRY (sex-determining region Y protein) status)
The classification of DSD is now based on a complete as possible description of the underlying abnormality as possible, beginning with:
- the sex chromosome type,
- presence of SRY (sex-determining region Y (SRY) protein)
- gonad type,
- tubular genitalia, and
- external genital phenotype
Look at these common disorders of sexual development?
What is the bovine freemartin?
The bovine freemartin is a genetic female born co-twin with a male => anastomoses develop between the placental vascular systems of the 2 foetuses => development of the gonads, tubular, and external genitalia of the female embryo altered by hormones and cells received through the common circulation with her male twin.
If anastomoses fail to develop, the female is not affected, but almost all male-female twinning in cattle results in the female becoming a freemartin.
What is your diagnosis?
A.Female Pseudohermaphrodite
B.Male Pseudohermaphrodite
C.True Hermaphrodite
B.Male Pseudohermaphrodite
Female outer genitalia and uterus as well, but also have things that are not ovaries, we have testes – epididymis.
The gonads are testes
what is your diagnosis?
A.Female Pseudohermaphrodite
B.Male Pseudohermaphrodite
C.True Hermaphrodite
C.True Hermaphrodite
Have uterus, may have ovaries on the left and the right ‘ovary’ doesn’t look like an ovary, it has endometria from 2 different gonadal tissues – some testicular tissue and areas with ovarian cortex, so have oval testes.
It is a true as have mixed gonadal tissue
Define Hermaphroditism?
Ambiguous genitalia, with part or all of the genital organs of both sexes present
Define True hermaphrodite?
Presence of both male and female gonadal tissue
Define Pseudohermaphrodite?
Presence of only a single type of gonadal tissue
→ Male pseudohermaphrodite (with testes)
→ Female pseudohermaphrodite (with ovaries)
Discuss Male reproductive system
Pathologies?
Disorders of sexual development
Cryptorchism, testicular hypoplasia, spermatic granuloma of the epididymal head, ambiguous genitalia…
Disorders of the scrotum
Disorders of the vaginal tunic
Disorders of the testis and epididymis
Decreased size
Cryptorchism, hypoplasia, segmental aplasia, testicular atrophy/degeneration
Increased size (including masses)
Spermatic granuloma of epididymal head, epididymitis, orchitis, periorchitis, testicular neoplasia, torsion…
Disorders of the accessory genital glands
Disorders of the penis and prepuce
Developmental anomalies, haemorrhage/haematoma, inflammation, neoplasia
Discuss disease of the scrotum?
Dermatitis is common
- •Trauma
- •Frost bite
- •Environmental irritants (e.g. cement dust)
- •Dermatophilus congolensis,
- •Besnoitia besnoiti (bull)
- •Choriotes bovis (ram)
→ Thermoregulatory failures
→ Testicular degeneration
Neoplasia:
- –Mast cell tumours (dog)
- –Haemangiosarcoma (dog)
- –Papilloma (boar)
*
Discuss Tunica vaginalis?
→ Thin layer of mesothelium around testis continuous with the
peritoneum.
- –Hydrocoele in ascites. (Image:Pig, scrotum: Hydrocoele.)
- –Periorchitis e.g. FIP, Glasser’s
- –Tumours (extension peritoneal tumour) very rare
Discuss disorders of Testis and Epididymis?
- Developmental anomalies
- Degeneration
- Inflammation
- Neoplasia
Discuss Cryptorchidism (small testis)?
- Incomplete descent of the testis
- Retained between kidney and inguinal canal
- Likely polygenetic basis
- Often hypoplastic
- Increased risk of tumour formation
Discuss testicular hypoplasia?
- Congenital or pre-puberty
- Often not observed until after puberty
- Nutrition, Zn def, genetic, endocrine abnormalities
- Occurs mostly cattle, sheep, goat
- Unilateral or bilateral
- Hypoplastic - normal consistency
- Microscopy: absent/ incomplete spermatogenesis with hypoplastic and normal tubules often intermingled
Discuss Testicular atrophy/
degeneration?
- After puberty
- Common cause for male infertility
- Causes: infections, ↑scrotal temperature, decreased testicular blood supply, vitamin A/ Zn deficiency, drug reactions, radiation damage, obstruction, hyperoestrogenism
- Unilateral or bilateral
- Small –firm consistency (chronic)
- Microscopic: similar to hypoplasia, (+/- fibrosis, multinucleated spermatids )
Photos:
A) TOP Ram: interstitial fibrosis that separates the seminiferous tubules. Spermatogenic arrest at the spermatocyte stage, vacuolation of Sertoli cells, and a wavy basement membrane caused by a reduction in tubular diameter are present.
B) BOTTOM Dog: In addition to reduced spermatogenesis, there is formation of multinucleated spermatids (arrows) as a result of failure of spermatids to separate. This is a common change in testicular degeneration.
Discuss Testis and epididymis
Inflammation?
Epididymitis >> orchitis (!)
Epididymitis:
- Important in rams (Brucella ovis – notifiable!) and dogs
- Almost always affects the tail of the epididymis
- Can cause secondary testicular degeneration/atrophy
- Mostly ascending infection (accessory glands, urinary tract)
- Rarer haematogenous (e.g. Brucella spp) or trauma
Discuss Spermatic granuloma of the epididymal head?
Spermatic granuloma of the epididymal head– congenital.
Abnormal blind-ended efferent ductules at puberty fill with spermatozoa à spermiostasis à spermatocele and then spermatic granulomas
Note on spermatic granulomas of the epididymal head: All efferent ductules should connect to the single epididymal duct in the head of the epididymis, but some are blind-ended. At puberty, the blind-ending ductules fill with spermatozoa and the resultant spermiostasis proceeds to spermatocele and then spermatic granulomas.
Look at theses pics of spermatic granuloma and epididymitis?
LEFT PIC - Spermatic granuloma, head of the epididymis, dog. A, The head of the epididymis is tremendously enlarged because of spermatic granulomas (white-yellow masses). The body and tail of the epididymis (ventral) are small, as the spermatic granulomas have obstructed the flow of spermatozoa from the testis to the epididymis.
RIGHT PIC - Epididymitis (Brucella ovis), tunic adhesions, epididymis, ram. Note the dramatic enlargement of the epididymis (left half of the image) and the adhesion of the parietal vaginal tunic to the visceral vaginal tunic around the affected epididymis.
Discuss Testicular neoplasia?
Which animals are they most common in?
What are the 3 main types?
- Most common in older dogs (>> horses)
–Common in older dogs, much less frequent in horses, and rare in o.ther species
- Three main primary types:
1. Interstitial (Leydig) cell tumour
2. Sertoli cell tumour.
3. Seminoma (germ cell tumour; also teratoma)
→ almost always benign!
- May also occur in combination
Discuss a Seminoma?
- Derived from spermatogonia
- 2nd most common dog; most common in aged stallions
- May cause swelling and pain
- Gross: cream bulging mass (looks like lymphoid tissue)
- Microscopy: sheets of polyhedral cells with a large nucleus and a thin rim of cytoplasm
- Mitoses are frequent
- More prevalent in retained testes
Discuss Sertoli cell tumours?
- 3rd most common testicular tumour in dogs
- 50% occur in retained testes
- Firm, white, lobulated mass.
- Testicular enlargement
- Colour: varies white to brown, often fibrous and may contain cysts.
- Microscopy: Sertoli cells multilayered in tubules or invading interstitial tissue. Abundant fibrous tissue
- Around 1/3 secrete oestrogen (and/ or inhibin) and cause feminisation of the affected dog (hyperoestrogenism).
- A possibly life-threatening effect of hyperestrogenism is myelotoxicity, resulting in a poorly regenerative anaemia, granulocytopenia, and thrombocytopenia.
Discuss Interstitial (Leydig) cell tumours?
- Most common testicular tumour dog, cat, bull
- Gross: single or multiple spherical, tan to orange or haemorrhagic masses (bulging on cut surface)
- No enlargement of the testis
- Microscopy: polyhedral cells packed in small groups by fine fibrous stroma
- Some produce hormones and cause aggression
Note: Aggression may be related to production of androgens by the tumour but most do not cause signs of hyperandrogenism.