LUT & MGT Flashcards
Diseases of the Ureters
-Congenital Anomalies
-Tumors and Tumor-Like Lesions
- Obstructive Lesions
Diseases of the Urinary Bladder
- Congenital Anomalies
- Inflammation
- Metaplastic Lesions
- Neoplasms
- Obstruction
Diseases of the Urethra
- Congenital Anomalies
- Regressive Changes
- Inflammation and Infections
- Vascular Disorders
- Spermatic Cord and Paratesticular Tumors
- Testicular Tumors
- Lesions of Tunica Vaginalis
Diseases of the Prostate Gland
- Inflammation
- Benign Enlargement
- Neoplasms
Ureter
Mucosa of these organs is lined by the uniquely
stratified urothelium or transitional epithelium
Composed of 5-6 layers of cells with oval nuclei with linear nuclear grooves, and a surface layer consisting of umbrella cells with abundant cytoplasm
Ureter mucosa
Lamina propria in the bladder form a
discontinuous muscularis mucosa
bladder cancers are staged on the basis of invasion of the
detrusor muscle (muscularis propria)
due to urine flow obstruction that causes the intravesical pressure to rise
Bladder hypertrophy
may entrap and obstruct the ureter
Retroperitoneal tumors or fibrosis
most common cause of hydronephrosis in infants and children
Ureteropelvic junction (UPJ) obstruction
Cases that present early in life preferentially affect males, are bilateral in 20% of cases, and are often associated with other anomalies
Ureteropelvic junction (UPJ) obstruction
More common in women and is most often unilateral
Ureteropelvic junction (UPJ) obstruction
Abnormal organization of smooth muscle bundles or excess stromal deposition of collagen between smooth muscle bundles at the UPJ, or in extrinsic compression of the UPJ by abnormal renal vessels
Ureteropelvic junction (UPJ) obstruction
- Typically of renal origin
- Usually small (5 mm in diameter or less)
- Impact at loci of ureteral narrowing—ureteropelvic junction, where ureters cross iliac vessels and where
they enter bladder—and cause excruciating “renal colic”
Calculi
May be congenital or acquired
Strictures
- Urothelial carcinomas arising in ureters
- Rarely, benign tumors or fibroepithelial polyps
Tumor (Intrisic)
Massive hematuria from renal calculi, tumors, or papillary necrosis
Blood Clots
Interruption of the neural pathways to the bladder
Neurogenic
Physiologic relaxation of smooth muscle or pressure on ureters at pelvic brim from enlarging fundus
Pregnancy
Salpingitis, diverticulitis, peritonitis, sclerosing retroperitoneal fibrosis
Periureteral Inflammation
With pelvic lesions associated with scarring
Endemetriosis
Cancers of the rectum, bladder, prostate, ovaries, uterus, cervix; lymphomas, sarcomas
Tumor (Extrinsic)
Intrinsic and extrinsic lesions may obstruct the ureters and may give rise to
hydroureter, hydronephrosis, and pyelonephritis
results from proximal intrinsic or extrinsic causes (stones, neoplasms etc.)
Unilateral obstruction
arises from distal causes, such as nodular hyperplasia of the prostate
Bilateral obstruction-
Fibrotic proliferative inflammatory process that encases retroperitoneal structures and causes hydronephrosis
Sclerosing Retroperitoneal Fibrosis
- Occurs in middle to late age and is more common in males
- IgG4-related disease
Sclerosing Retroperitoneal Fibrosis
Sclerosing Retroperitoneal Fibrosis
Treatment for this disease are: corticosteroids, ureteral stents or surgical extrication of the ureters (ureterolysis)
Sclerosing Retroperitoneal Fibrosis
MORPHOLOGIC FINDING:
Fibrous tissue containing a prominent infiltrate of lymphocytes, often with germinal centers, plasma cells (frequently IgG4-positive), and eosinophils
Sclerosing Retroperitoneal Fibrosis
Associated with increased risk of infection or neoplasia
Diseases of the Urinary Bladder
- Most common and serious congenital anomaly
- Can lead to ascending pyelonephritis and loss of renal function
- Can give rise to congenital vesicouterine fistulae
Diverticula
- Developmental failure in the anterior wall of the abdomen and the bladder
- Bladder communicates directly with the abdominal surface
- Exposed bladder mucosa may undergo colonic glandular metaplasia and is subject to chronic infection that spreads to the upper urinary tract
- Associated with an increased risk of adenocarcinoma in the bladder remnant
Exstrophy of the bladder
- Urachal canal connects the fetal bladder with the allantois and normally is obliterated at birth
- Patent urachus creates a fistulous urinary tract connection between the bladder and umbilicus
- When only a central region of patent urachus persists, a urachal cyst lined by urothelial or metaplastic glandular epithelium is formed
- Urachal cysts are at increased risk for neoplastic transformation (adenocarcinoma)
Urachal Anomalies
Bacterial pyelonephritis is frequently preceded by infection of the urinary bladder, with retrograde spread of microorganisms into the kidneys and their collecting systems
Acute and Chronic Cystitis
bladder calculi, urinary obstruction, diabetes mellitus, instrumentation, and immune deficiency
Acute and Chronic Cystitis
- ## Most common: E. coli, Proteus, Klebsiella and EnterobacterWomen are more prone due to shorter urethras
Coliform
TB cystitis leading to renal TB
Mycobacteria
Candida and cryptococcal cystitis (immunosuppressed)
Fungal
- Bladder schistosomiasis
- More common in african and middle eastern countries
Schistosomiasis haematobium
Hemorrhagic cystitis
BK Virus
Emphysematous cystitis
Clostridium
Viral (adenovirus), Chlamydia and Mycoplasma
Others
Morphologic Findings
hyperemia of the mucosa and neutrophilic infiltrate, sometimes associated with exudate
Aute Cystitis
Morphologic Findings
caused by persistent acute cystitis associated with mononuclear inflammatory infiltrates
Chronic Cystitis
Morphologic Findings
systemic chemotherapy or pelvic irradiation
Iatrogenic Cystitis
Morphologic Findings
cyclophosphamide (hemorrhagic cystitis)
Cytotoxic Cystitis
Morphologic Findings
infiltration of the submucosa by eosinophils (nonspecific subacute inflammation) and may also be a manifestation of a systemic allergic disorder
Eosinophilic Cystitis
Morphologic Findings
presence of lymphoid follicles within the bladder mucosa and underlying wall
Follicular Cystitis
cystitis triad of symptoms
- Frequency (urination every 15 to 20 minutes)
- Lower abdominal pain localized over the bladder region or in the suprapubic region
- Dysuria (pain or burning on urination)
Infections may be antecedents to pyelonephritis
cystitis
sometimes a secondary complication of an underlying disorder associated with urinary stasis, such as prostatic hypertrophy, cystocele, calculi, or bladder neoplasms
Cystitis
- Disorder of unknown etiology that occurs most frequently in women
- Unpleasant sensation (pain, pressure, discomfort) related to the urinary bladder, associated with urinary tract symptoms of >6 weeks duration, in the absence of infection or other identifiable causes
Interstitial Cystitis (Chronic Pelvic Pain Syndrome)
- Intermittent, often severe, suprapubic pain; urinary frequency; urgency; hematuria; and dysuria
- Cystoscopic findings: mucosal fissures and punctate hemorrhages (glomerulations)
Interstitial Cystitis (Chronic Pelvic Pain Syndrome)
- Late (classic ulcerative) phase: associated with chronic mucosal ulcers (Hunner ulcers)
- Transmural fibrosis may lead to a contracted bladder
Interstitial Cystitis (Chronic Pelvic Pain Syndrome)
- Pathologic findings are non-specific; mast cells are often increased in the submucosa
- Clinically mimics interstitial cystitis
- Treatment is largely empiric
Interstitial Cystitis (Chronic Pelvic Pain Syndrome)
- Chronic inflammatory reaction that appears to stem from acquired defects in phagocyte function
- Arises in the setting of chronic bacterial infection, mostly by E. coli or occasionally Proteus species
-Occurs with setting of immunosuppression
Malakoplakia
-Soft yellow, slightly raised mucosal plaque (3-4cm)
-Macrophages have abundant granular cytoplasm
- Michaelis-Gutmann bodies: deposition of calcium in enlarged lysosomes
Malakoplakia
- Inflammatory lesion resulting from irritation of the bladder mucosa, most commonly as a result of instrumentation (indwelling catheters)
- May be mistaken for papillary urothelial carcinoma, both clinically and histologically.
Polypoid Cystitis
- Common lesions of the urinary bladder in which nests of urothelium (von Brunn nests) grow downward into the lamina propria
Cystitis Glandularis and Cystitis Cystica
metaplasia that take on cuboidal or columnar appearance
Cystitis glandularis
epithelial cells retract to produce cystic spaces
Cytitis cystica
- These 2 processes often coexist: cystitis cystica et glandularis
- Both variants can arise in the setting of inflammation and metaplasia
- Extensive and multifocal intestinal metaplasia is a precursor to adenocarcinoma
Cytitis cystica
Cystitis glandularis
- Response to chronic injury
- Urothelium is often replaced by non- keratinizing or keratinizing squamous epithelium, which is a more durable lining
Squamous Metaplasia
- Extensive multifocal keratinizing squamous metaplasia is a precursor to dysplastic lesions and in situ and invasive squamous cell CA
- Seen with bladder schistosomiasis
Squamous Metaplasia
- May not be a form of true metaplasia
- Some of these lesions are caused by implantation and growth of renal tubular cells at sites of bladder mucosa erosion
Nephrogenic adenoma
- Overlying urothelium is focally replaced by cuboidal epithelium (papillary pattern)
- Larger lesions can raise a suspicion of cancer
Nephrogenic adenoma
is the ninth most common cancer type worldwide and is responsible for significant morbidity and mortality
Bladder cancer
*95% of bladder tumors are of _________, with _________ being by far the most common type followed by _____ and ____________
epithelial origin
urothelial neoplasms
squamous
glandular neoplasms
- Non-invasive tumors
- Infiltrating urothelial carcinoma
- Variants: nested, microcystic, micropapillary, plasmacytoid, sarcomatoid, giant cell, poorly differentiated, lipid-rich, and clear cell
Urothelial (transitional) tumors
- Adenocarcinoma
- Squamous cell carcinoma
- Mixed carcinoma
- Small-cell carcinoma
- Sarcomas
Other tumors of the bladder
- Represent about 90% of all bladder tumors
- May be seen at any site where there is urothelium, from the renal pelvis to the distal urethra
Urothelial Neoplasms
most common precursor lesions which originate from papillary urothelial hyperplasia
Non-invasive papillary tumors
other precursor lesion to invasive carcinoma (CIS)
Flat non-invasive urothelial carcinoma
term used to describe epithelial lesions that have the cytologic features of malignancy but are confined to the epithelium, showing no evidence of basement membrane invasion
Carcinoma in-situ
- Although invasion into the lamina propria worsens the prognosis, the major decrease in survival is associated with invasion of the _______
muscularis propria (detrusor muscle)
- higher in men (male-to-female ratio of 3: 1), in higher income nations, and in urban dwellers
- About 80% of patients are between 50 and 80 years of age
- ______ is not familial
neoplas,
bladder cancer
Several factors :
- Cigarette smoking
- Industrial exposure to aryl amines (2-naphthylamine)
- Schistosoma haematobium
- Long-term use of analgesics
- Heavy long-term exposure to cyclophosphamide
- Pelvic irradiation
Urothelial Neoplasms
gain-of-function alterations that increase signaling through growth factor receptor pathways
Non–muscle-invasive papillary cancers
- Amplifications of the FGFR3 tyrosine kinase receptor gene
- Activating mutations in the genes encoding RAS and PI3-kinase
- These tumors frequently recur but progress to muscle- invasive bladder cancer in only about 20% of cases
Urothelial Neoplasms
Flat CIS
majority of muscle-invasive bladder cancers
- Gross: can be purely papillary to nodular or flat
- Papillary lesions are red, elevated excrescences (1-5 cm)
- Multiple discrete tumors are often present
Urothelial Neoplasms
- Represent 1% of bladder tumors and are often seen in younger patients
- Typically arise singly as small (0.5 to 2 cm)
Papilloma
delicate structures superficially attached to the mucosa by a stalk
Exophytic papillomas
- Finger-like papillae covered by epithelium that is histologically identical to normal urothelium
- Recurrences and progression are rare but may occur
Papillomas
completely benign lesions consisting of inter-anastomosing cords of cytologically bland urothelium that extend down into
the lamina propria; they simulate an invasive process
Inverted papillomas
- Histologically similar with papillomas, differing only in having thicker urothelium with greater density of cells
- Tend to be larger than papillomas and may be indistinguishable from papillary cancers
- Progression to tumors of higher grade may occur but is rare
Papillary urothelial neoplasms of low malignant potential (PUNLMP)
- Orderly architectural appearance and low- grade cytologic atypia
- Cells are evenly spaced (maintain polarity) and cohesive
- Scattered hyperchromatic nuclei, infrequent mitotic figures toward the base, and slight variation in nuclear size and shape
- May recur and, infrequently, may also invade
Low-grade papillary urothelial carcinomas
- Contain dyscohesive cells with large hyperchromatic nuclei, irregular nuclear chromatin, and prominent nucleoli
- Highly anaplastic with mitotic figures
- There is disarray and loss of polarity
- Can progress to muscle-invasive bladder
cancer and metastasis to regional LN and systemic spread (and lung)
High-grade papillary urothelial carcinomas
- Defined by the presence of cytologically malignant cells within a flat urothelium
- May range from full-thickness cytologic atypia to scattered malignant cells (pagetoid spread)
- Common feature shared with highgrade papillary urothelial carcinoma is a lack of cohesiveness, which leads to shedding of malignant cells into the urine
Flat urothelial carcinoma (CIS)
- Cystoscopy: area of mucosal reddening, granularity, or thickening
- Commonly multifocal and may involve most of the bladder surface and extend into the ureters and urethra
- If untreated, it progresses to invasive cancer
Flat urothelial carcinoma (CIS)
- Associated with papillary urothelial cancer, usually high grade, or adjacent CIS
- Extent of spread (stage), based primarily on depth of invasion in the bladder wall
- Invasion of the muscularis propria layer is an indication for radical cystectomy or radiation
therapy with neoadjuvant or adjuvant chemotherapy
Invasive urothelial carcinoma
- Urothelial proliferation of uncertain malignant potential (flat hyperplasia)
- Urothelial dysplasia
- Urothelial carcinoma in situ
Flat Lesions
- Papilloma
- Urothelial proliferation of uncertain malignant potential (papillary hyperplasia)
- Papillary urothelial neoplasms of low malignant potential
- Papillary urothelial carcinoma, low grade
- Papillary urothelial carcinoma, high grade
Exophytic Papillary Lesions
- Painless hematuria is the most common symptom of bladder cancer
- Frequency, urgency, and dysuria may accompany hematuria
- Obstruction of the ureteral orifice may lead to pyelonephritis or hydronephrosis.
Urothelial Neoplasm
Initial treatment of non–muscle-invasive tumors
- Localized low-grade papillary tumors- diagnostic transurethral resection is the only procedure needed
- CIS and large, high grade, multifocal, recurrence, or are associated with lamina propria invasion are treated with intravesical instillation of an attenuated strain of BCG
radical cystectomy or cystoprostatectomy, or radiation with chemotherapy
Muscle-invasive bladder carcinoma
Radical cystectomy is also indicated in cases of:
- CIS or high-grade papillary cancer refractory to BCG and other intravesical therapies
- CIS extending into the prostatic urethra and ducts
- Occasional cases of non–muscle-invasive papillary urothelial high-grade carcinoma
Most metastatic tumors respond poorly to chemotherapy, which produces 5-year survival rates of only _____
15%
- Make up 3% to 7% of bladder cancers
- Much more frequent in countries where urinary schistosomiasis is endemic
- Arise from atypical keratinizing mucosa (squamous dysplasia and CIS)
- Always associated with chronic bladder irritation and infection
Squamous Cell CA
- More frequent than pure squamous cell CA
- Most are invasive, fungating tumors or are infiltrative and ulcerative
- Can produce abundant keratin to anaplastic
tumors with only focal evidence of squamous differentiation
Mixed urothelial carcinoma with areas of squamous carcinoma
- Rare and histologically identical to adenocarcinomas seen in the GIT
- Some arise from urachal remnants or in association w/ extensive intestinal metaplasia
Adenocarcinoma
- Indistinguishable from small-cell carcinomas of the lung, occasionally arise in the bladder, often in association with urothelial, squamous, or adenocarcinoma
- Strongly associated with loss-of-function of TP53 and RB tumor suppressor genes
Small Cell Carcinoma
- Most common is leiomyoma
- They tend to grow as isolated, intramural
(submucosal), encapsulated, ovalto-spherical masses up to several centimeters in diameter.
Benign Tumors
- Inflammatory myofibroblastic tumors and various carcinomas that assume sarcomatoid growth patterns are more common
- Large masses (15 cm in diameter) that protrude into the vesicle lumen
- Soft, fleshy, gray-white gross appearance
- Most common bladder sarcoma in infancy or childhood is embryonal rhabdomyosarcoma
- Polypoid grape-like mass (sarcoma botryoides)
Sarcoma
secondary malignant involvement of the bladder is most often due to direct extension of cancers arising in adjacent organs, mainly the cervix, uterus, prostate, and rectum
Secondary Tumors
Obstruction of the bladder outlet is of major clinical importance because of its eventual effect on the kidney
- Males- ________
- Females- __________
benign prostatic hyperplasia (BPH)
cystocele of the bladder
- Congenital urethral strictures
- Inflammatory urethral strictures
- Inflammatory fibrosis and contraction of the bladder
- Bladder tumors, either benign or malignant
- Invasion of the bladder neck by tumors arising in contiguous organs
- Mechanical obstructions by foreign bodies and calculi
- Injury of nerves controlling bladder contraction (neurogenic bladder)
Obstruction of Bladder Outlet Causes
MORPHOLOGIC FINDINGS
- Early stages: there is only thickening of the bladder wall due to smooth muscle hypertrophy
- Trabeculation of the bladder wall due to progressive hypertrophy
- Crypts form and may be converted into diverticula
- Enlarged bladder may reach the brim of the pelvis or umbilicus
Bladder Outlet Obstructions
earliest manifestations of venereal infection
Gonococcal Urethritis
common and can be caused by several different organisms
Nongonococcal urethritis
Often accompanied by cystitis in women and by prostatitis in men
Inflammation of Urethra
Reactive arthritis (Reiter syndrome), which is associated with the clinical triad of _____
arthritis, conjunctivitis, and urethritis
- inflammatory lesion that presents as a small, red, painful mass about the external urethral meatus, typically in older females
- It consists of inflamed granulation tissue covered by an intact but friable mucosa, which may ulcerate and bleed with the slightest trauma
- Surgical excision affords prompt relief and cure
Urethral caruncle
squamous and urothelial papillomas, inverted urothelial papillomas, and condylomas
Benign Epithelial Tumor
urothelial differentiation and are analogous to those occurring within the bladder
Proximal Urethra
squamous cell carcinomas and HPV-related
Distal Urethra
- Malformation of the urethral groove and canal may create an abnormal opening either on the ventral surface of the penis (hypospadias) or on the dorsal surface (epispadias)
- Associated with failure of normal descent of the testes and with malformations of urinary tract
- Hypospadias- more common of the two
- Abnormal opening is often constricted, resulting in urinary tract obstruction and an increased risk of ascending infections
- Normal ejaculation and insemination are hampered and may be a cause of sterility
Hypospadias & Epispadias
- Orifice of the prepuce is too small to permit its normal retraction
- May result from anomalous development but is more frequently the result of repeated bouts of infection that cause scarring of preputial ring
- It interferes with cleanliness, favoring the
development of secondary infections and penile carcinoma
Phimosis
Almost invariably involve the glans and prepuce and include a wide variety of specific and nonspecific infections
Penis Inflammation
syphilis, gonorrhea, chancroid, granuloma inguinale, lymphopathia venerea, genital herpes
Specific Infections are STIs
refers to non-specific infection of the glans and prepuce caused by a wide variety of organisms
Balanophostits
- More common agents are C. albicans, anaerobic bacteria,
Gardnerella, and pyogenic bacteria - Consequence of poor local hygiene in uncircumcised males
- Persistence of such infections leads to inflammatory scarring and, is a common cause of phimosis.
Balanophostitis
benign sexually transmitted wart caused by HPV (serotypes 6 and 11)
Condyloma Acuminatum
- It is related to the common wart and may occur on any moist mucocutaneous surface of the external genitals
- May arise in the external genitalia or perineal areas
- Penile lesions usually occur in the coronal sulcus and inner surface of the prepuce
Condyloma Acuminatum
Gross:
- consist of single or multiple sessile or pedunculated, red papillary excrescences
Microscopic:
- branching, villous, papillary connective tissue stroma is covered by epithelium with superficial hyperkeratosis and thickening of the underlying epidermis (acanthosis)
- Normal orderly maturation of the epithelial cells is preserved
- Lining cells frequently display perinuclear cytoplasmic
vacuolization (koilocytosis), characteristic of HPV infection
Condyloma Acuminatum
to be reactive rather than neoplastic, is characterized by hard penile plaques that result from the deposition of collagen in the connective tissue between the corpora cavernosa and the tunica albuginea
Peyronie Disease
- Fibrosis is the product of microvascular trauma and subsequent organizing sclerosing chronic inflammation
- Results in penile curvature toward the side of the lesion and pain during intercourse
- Treatments: surgery and injection of collagenase
Peyronie Disease
- These lesions are encompassed by the umbrella term penile intraepithelial neoplasia (PeIN)
- All are squamous lesions confined to the epidermis by an intact basement membrane
Squamous Carcinoma in situ/Penile Intraepithelial Neoplasia
Associated with balanitis xerotica obliterans, occurs on the foreskin of older patients, and as the name implies retains a degree of squamous maturation
Non–HPV-related (differentiated)
- Composed of more overtly malignant cells
- May manifest clinically as two distinct lesions:
Bowen disease
Bowenoid papulosis - Both are associated with high-risk HPV (HPV 16)
HPV-related (undifferentiated PeIN)
- Affects the penile shaft and scrotum of older men
- Solitary, thickened, gray-white, opaque plaque
- When it affects the glans, the lesion acquires a velvety red appearance
- Dysplastic squamous cells containing large hyperchromatic irregular nuclei and lacking orderly maturation with atypical numerous mitoses
- Gives rise to infiltrating squamous cell carcinoma
Bowen Disease
- Occurs in sexually active adults
- It is distinguished from BD by the younger age of affected patients and its presentation as multiple (rather than solitary) reddish brown papular lesions
- Virtually never develops into invasive carcinoma and usually regresses spontaneously.
Bowenoid Papulosis
Associated with poor genital hygiene and high-risk HPV infection
- Affects middle-aged and older patients (40 to 70 years of age)
- Low income status and poor hygiene habits are salient risk factors
- Circumcision confers protection, more common in populations in which circumcision is not practiced routinely
Invasive Cell Carcinoma
TRUE OR FALSE
Availability of vaccines to both low-risk and high-risk subtypes of HPV may help reduce the incidence of penile cancer and condyloma acuminatum
TRUE
Other risk factors:
cigarette smoking and chronic inflammatory conditions such as lichen sclerosis et atrophicus (balanitis xerotica obliterans)
Invasive Squamous Cell Carcinoma
PATHOGENESIS:
- HPV encode E6 and E7 proteins that inactivate the p53 and RB tumor suppressor proteins, leading to genomic instability and increased proliferation, respectively
E6 protein also stimulates telomerase expression, leading to cellular immortalization
E7 protein induces feedback loops that increase levels of the CDKi p16
Invasive Squamous Cell Carcinoma
- Slowly growing, locally invasive lesion that often has been present for a year or more before
- Lesions are nonpainful until they undergo secondary ulceration and infection
- Metastases to inguinal LNs may occur early in its course
- Only 50% of enlarged inguinal nodes detected in men with penile SCC contain cancer, with the remainder showing only reactive lymphoid hyperplasia
Invasive Squamous Cell Carcinoma
Morphologic Findings:
Location
- originates in glans or inner surface of the prepuce near the coronal sulcus
Gross:
- may be irregular, fungating cauliflower-like masses; flat, indurated lesions; or large verruciform/papillary tumors
- Conventional (usual) SCC is the most common HPV-negative type, encompassing almost half of all penile cancers
Invasive Squamous Cell Carcinoma
Histologic subtypes are associated with distinct grades:
- Verrucous and papillary carcinomas are well differentiated/grade 1 tumors
- Sarcomatoid and basaloid carcinomas are poorly differentiated/grade 3 tumors
Invasive Squamous Cell Carcinoma
exophytic, warty well-differentiated, non–HPV-related variant that invades locally along a broad pushing border, but rarely metastasizes
Verrucious Carcinoma
HPV-related tumor comprised of
relatively small hyperchromatic cells that has a destructive pattern of invasion and usually pursues an aggressive course
Basaloud Carcinoma
