Diseases of the liver and pancreas

Tumor cells varies from small cells with moderately hyperchromatic regular nuclei to huge cells with large irregular and hyperchromatic nuclei

Frequently, invasion of perivascular and perineural spaces as well as blood and lymphatic vessels is readily evident

Tumors are graded according to

Degree of nuclear atypia

Histologic differentiation (tubule formation) into

Well differentiated

Moderately differentiated

Poorly differentiated

Tumor cells in cords and tubules infilterating stroma

Medullary Carcinoma

• ~1 to 5% of all mammary carcinomas

• Average size is 2 to 3 cm, but some produce large, fleshy tumor masses up to 5 cm in diameter or greater

• On section

• Has a soft, fleshy consistency and tends to be discrete

• Foci of necrosis and hemorrhage are large and numerous

• Histologically, the carcinoma is characterized by

• Solid, syncytium-like sheets of large cells with vesicular, often pleomorphic nuclei, containing prominent nucleoli and frequent mitoses (the syncytial cells occupy more than 75% of the tumor)

• Moderate-to-marked lymphocytic infiltrate between these sheets

• Scant fibrous component

• Distinctly better prognosis than the usual infiltrating duct carcinomas, even in the presence of axillary lymph node metastases

• The ten-year survival rate is more than 70%.

Medullary Carcinoma

Invasive Lobular Carcinoma

• 5-10%

• Bilateral more frequently than others

• Multicentric within the same breast

• More frequently metastasize to CSF, serosal surfaces, ovary and uterus, and bone marrow as compared to other subtypes

Colloid or Mucinous Carcinoma

• Unusual variant

• Occurs in older women

• Grows slowly over the course of many years

• The tumor is extremely soft

• Consistency and appearance of pale gray-blue gelatin

• Pure form

  • 75% of the tumor is mucinous or mixed, in association with other types of infiltrating duct carcinoma.

  • Large lakes of lightly staining, amorphous mucin that dissect and extend into contiguous tissue spaces and planes of cleavage

  • Floating within this mucin are small islands and isolated neoplastic cells, sometimes forming glands

  • Vacuolation of at least some of the cells is characteristic

• “Mixed” mucinous tumors

  • Large areas with mucin + areas of typical nonmucinous invasive duct carcinoma.

• Lakes of mucin

• Islands of tumor cells

ID/CC A 52 year old unmarried white nulliparous female smoker with early menarche presents with a painless lump in her right breast.

HPI The patient has a history of atypical hyperplasia of the right breast. Her mother died of breast cancer at age 46.

PE A 3 cm, fixed, hard, and nontender mass in the upper outer quadrant of right breast; retraction of overlying skin and nipple; no nipple discharge; palpable axillary lymph nodes on right side

Imaging

Mammo: spiculated mass with architectural distortion and multiple clustered pleomorphic microcalcifications; skin thickening and retraction

Peau ‘D Orange

OVARIAN TUMORS

• 
  Among cancers of the female genital tract, the incidence of ovarian cancer ranks below only carcinoma of the cervix and the endometrium.
  
• 
  There are numerous types of ovarian tumors, both benign and malignant.
  

• 
  About 80% are benign, and these occur mostly in young women between the ages of 20 and 45 years.
  
• 
  The malignant tumors are more common in older women, between the ages of 40 and 65 years.
  
• 
  Risk factors for ovarian cancer are much less clear than for other genital tumors
  
• 
  General agreement on two risk factors:
  

• 
  nulliparity
  
• 
  family history
  

• 
  The most intriguing risk factor is genetic and candidate host genes, which may be altered in susceptible families (i.e., ovarian cancer genes). Several are being considered, and at least one (BRCA1) increases susceptibility to breast cancer and resides on chromosome 17q21.
  
• 
  Approximately 30% of ovarian adenocarcinomas express high levels of HER-2/neu oncogene, which correlates with a poor prognosis.
  
• 
  Mutations in a host tumor suppressor gene p53 are found in 50% of ovarian carcinomas.
  

TYPES OF OVARIAN TUMORS

• 
  THREE main types of PRIMARY ovarian tumors:
  

• 
  Epithelial ovarian tumors:
  

• 
  Derived from the cells on the surface of the ovary.
  
• 
  Most common form of ovarian cancer
  
• 
  Occur primarily in adults
  

• 
  Germ cell ovarian tumors:
  

• 
  Derived from the egg producing cells within the
  

body of the ovary.

• 
  Occur primarily in children and teens
  
• 
  Rare by comparison to epithelial ovarian tumors
  

• 
  Sex cord stromal ovarian tumors
  

• 
  Also rare in comparison to epithelial tumors
  
• 
  Often produces steroid hormones
  

• 
  Cancers derived from other organs can also spread to the ovaries (METASTATIC cancers).
  

Distribution of Benign Ovarian Neoplasms Distribution of Malignant Ovarian Neoplasms

Tumors of Surface (Coelomic) Epithelium

• 
  Most of the primary neoplasms in the ovary arise from the surface epithelium.
  
• 
  Types :
  

• 
  Serous
  
• 
  Mucinous
  
• 
  Endometrioid
  
• 
  Clear cell carcinoma
  
• 
  Brenner’s tumor
  
• 
  Cystadenofibroma
  

• 
  Mixtures of these epithelia frequently occur in the same tumor
  

Tumors of Surface (Coelomic) Epithelium

• 
  Benign tumors  Tumors of borderline malignancy malignant tumors
  
• 
  Range in size and composition
  

• 
  Size:
  

• 
  Small and grossly imperceptible or massive, filling the pelvis and even the abdominal cavity.
  

• 
  Components of the tumors:
  

• 
  cystic areas (cystadenomas)
  
• 
  cystic and fibrous areas (cystadenofibromas)
  
• 
  fibrous areas (adenofibromas)
  

• 
  On gross examination, the risk of malignancy increases as a function of the amount of discernible solid epithelial growth, including papillary projections of soft tumor, thickened tumor lining the cyst spaces, or solid necrotic friable tissue depicting necrosis
  

• 
  Although termed epithelial in differentiation, these tumors are derived from coelomic mesothelium
  

• 
  Has the capability to evolve into different types of epithelia present in the normal female genital tract
  

• 
  serous (tubal)
  
• 
  endometrioid (endometrium)
  
• 
  mucinous (cervix)
  

Serous Tumors

• 
  Account for about 30% of all ovarian tumors
  
• 
  Biologic behavior of serous tumors depends on
  

• 
  Degree of differentiation
  
• 
  Distribution of the tumor
  

• 
  Ovarian surface
  
• 
  Peritoneal surface
  

• 
  Prognosis is closely related to
  

• 
  histologic appearance of the tumor
  
• 
  growth pattern on the peritoneum.
  

• 
  Benign + Borderline
  

• 
  Approx 75%
  
• 
  Are most common between the ages of 20 and 50
  
• 
  Borderline tumors can originate from or extend to the peritoneal surfaces
  
• 
  May remain localized  causing no symptoms; or
  
• 
  Spread slowly  producing intestinal obstruction / other complications after many years
  
• 
  5-year survival for borderline tumors
  

• 
  confined within the ovarian mass is 100%
  
• 
  involving the peritoneum is about 90%
  

• 
  Malignant
  

• 
  Approx 25%
  
• 
  Serous Cystadenocarcinomas occur later in life on average
  

• 
  Serous cystadenocarcinomas account for approximately 40% of all cancers of the ovary
  
• 
  Are the most common malignant ovarian tumors.
  

• 
  Infiltrate the soft tissue and form large intra-abdominal masses and rapid deterioration
  
• 
  The 5-year survival for malignant tumors confined within the ovarian mass is 70%, involving the peritoneum is 25%
  

• 
  For this reason, careful pathologic classification of the tumor, even if it has extended to the peritoneum, is relevant to both prognosis and selection of therapy.
  
• 
  Unencapsulated serous tumors of the ovarian surface are more likely to extend to the peritoneal surfaces
  

Gross morphology

• 
  One or a few fibrous walled cysts
  
• 
  10-15 cm in diameter and occasionally up to 40 cm.
  
• 
  Bilaterality is common
  

• 
  Benign: ( e.g: Benign serous cystadenoma)
  

• 
  Contain a smooth glistening cyst wall with no epithelial thickening or small papillary projections (i.e., papillary cystadenoma)
  
• 
  20% bilateral
  

• 
  Borderline tumors
  

• 
  Contain an increasing amount of papillary projections
  
• 
  30% bilateral
  

• 
  Malignant: (Malignant serous cystadenocarcinoma)
  

• 
  Large amounts of solid or papillary tumor mass
  
• 
  Irregularity in the tumor mass
  
• 
  Fixation or nodularity of the capsule
  
• 
  66% bilateral
  

Benign Serous Cystadenoma

• 
  Smooth glistening cyst wall
  
• 
  Multiloculated smooth glistening cyst wall with no epithelial thickening or papillary projections
  
• 
  MRI
  

Borderline serous cystadenoma – cavity lined by delicate papillary structures

Papillary serous cystadenoma

Papillary serous cystadenocarcinoma

• 
  Predominately cystic but the granular excresences on the lower half of the mass indicate peritoneal extension.
  
• 
  Papillary serous cystadenocarcinoma
  
• 
  Note the many papillations on the inner surface.
  

Cystadenocarcinoma – opened to reveal large bulky tumor mass

Histology of serous tumors

• 
  Benign tumors
  

• 
  Lining epithelium is composed of columnar epithelium
  
• 
  With abundant cilia
  
• 
  Microscopic papillae may be found
  

• 
  Borderline malignancy
  

• 
  Lining epithelium is composed of columnar epithelium
  
• 
  Increased complexity of the stromal papillae with stratification of the epithelium and nuclear atypia
  
• 
  Destructive infiltrative growth into the stroma is not seen.
  

• 
  Malignant / Cystadenocarcinomas
  

• 
  Even more complex growth with infiltration or frank effacement of the underlying stroma by solid growth
  
• 
  The individual tumor cells in the carcinomatous lesions display the usual features of all malignancy, and with the more extreme degrees of atypia, the cells may become quite undifferentiated.
  

• 
  The presence of concentric calcifications (psammoma bodies) characterizes serous tumors, although they are not specific for neoplasia when found alone.
  

Borderline serous cystadenoma

• 
  Papillary projections of epithelium extending
  

into the lumen of the tumor.

• 
  There is no invasion of the stroma or capsule.
  

Borderline papillary serous tumor

• 
  Note absence of stromal invasion
  

• 
  High power view of papillary tuft in borderline serous tumor., Note cellular pleomorphism.
  

Papillary serous cystadenocarcinoma

• 
  More pronounced papillary growth with more hyperchromatic cells
  
• 
  showing malignant glands invading stroma.
  
• 
  Psammomma bodies- papillary serous cystadenocarcinomas
  

• 
  Small concretions seen here as purplish rounded and laminated objects.
  
• 
  Essentially a form of dystrophic calcification in neoplasms.
  

Mucinous Tumors

• 
  Closely resemble their serous counterparts.
  
• 
  Less common  25% of all ovarian neoplasms.
  
• 
  Occur principally in middle adult life
  
• 
  Rare before puberty and after menopause.
  
• 
  Benign or borderline: 80%
  
• 
  Malignant: 15%
  

• 
  Mucinous cystadenocarcinomas are relatively uncommon
  
• 
  Account for only 10% of all ovarian cancers.
  

Gross Morphology

• 
  Differences from serous tumors:
  
• 
  More cysts of variable size
  
• 
  Less frequently bilateral.
  

• 
  Approximately 5% of mucinous cystadenomas and 20% of mucinous cystadenocarcinomas are bilateral.
  

• 
  Mucinous tumors tend to produce larger cystic masses, and some have been recorded with weights of more than 25 kg.
  
• 
  Grossly they appear as multiloculated tumors filled with sticky, gelatinous fluid rich in glycoproteins
  

Histology of mucinous tumors

• 
  Characterized by a lining of tall columnar epithelial cells with apical mucin and the absence of cilia
  

• 
  similar to benign cervical or intestinal epithelia
  

• 
  Borderline tumors exhibit abundant gland-like or papillary growth with nuclear atypia and stratification
  

• 
  Appear similar to tubular adenomas or villous adenomas of the intestine.
  

• 
  Cystadenocarcinomas contain more solid growth with conspicuous epithelial cell atypia and stratification, loss of gland architecture and necrosis
  

• 
  Are similar to colonic cancer in appearance
  

Mucinous cystadenoma, ovary, medium power Mucinous cystadenoma

• 
  Cyst wall lined by mucous containing tall Mucinous cystadenoma with basally placed
  

columnar epithelial cells. nuclei and apical mucin. Four locules are

• 
  These mucin secreting cells have characteristics present in this section. Note resemblance
  

of intestinal type differentiation, endocervical to endocervical type epithelium

type differentiation can also be seen

Borderline mucinous tumor

• 
  Showing papillary configuration of lining epithelium
  
• 
  High power view. Note nuclear stratification.
  

Mucinous cystadenocarcinoma. Pseudomyxoma peritonei

• 
  Note bulging, glistening cysts filled with mucin
  

Pseudomyxoma peritonei

• 
  Mucinous tumors (like serous tumors) may involve the peritoneal surface with collection of extensive mucinous material resembling cystic contents within the peritoneal cavity
  
• 
  Is a rare condition
  
• 
  Seen with primarily borderline or malignant neoplasms.
  
• 
  Major complication:
  

• 
  Extensive interadherence and adhesion of the viscera, producing a matting together of the abdominal contents and intestinal obstruction
  

Endometrioid Tumors

• 
  Approximately 20% of all ovarian cancers
  
• 
  Most endometrioid tumors are carcinomas.
  

• 
  Less commonly, benign forms–usually cystadenofibromas–are encountered.
  

• 
  Distinguished from serous and mucinous tumors by the presence of tubular glands bearing a close resemblance to benign or malignant endometrium.
  
• 
  15 to 30% of endometrioid carcinomas are accompanied by a carcinoma of the endometrium
  
• 
  About 15% of cases with endometrioid carcinoma coexist with endometriosis
  

Morphology

• 
  Grossly, endometrioid carcinomas present as a combination of solid and cystic areas, similar to other cystadenocarcinomas
  
• 
  40% bilateral
  

• 
  bilaterality usually implies extension of the neoplasm beyond the female genital tract.
  

Endometrioid adenocarcinoma

• 
  Glandular patterns bearing a strong resemblance to endometrial origin
  
• 
  Well-differentiated endometrioid adenocarcinoma. Glands show irregular budding but have smooth contours
  

• 
  High power view showing well-formed glands with nuclear stratification.
  

Clear Cell Adenocarcinoma

• 
  Uncommon
  
• 
  Characterized by large epithelial cells with abundant clear cytoplasm.
  
• 
  Can be predominantly solid or cystic.
  
• 
  In the solid neoplasm, the clear cells are arranged in sheets or tubules.
  
• 
  In the cystic variety, the neoplastic cells line the spaces.
  
• 
  The 5-year survival rate is approximately 50% when the tumors are confined to the ovaries
  

• 
  Tend to be aggressive, and with spread beyond the ovary, a survival of 5 years is exceptional.
  

Clear Cell Adenocarcinoma


Clear Cell Adenocarcinoma

• 
  Tumor cells with clear well-defined borders and abundant pale or clear cytoplasm containing a small, often eccentric nucleus, lining tubules or cysts or forming solid sheets
  

• 
  Showing a tubulopapillary pattern with prominent hobnail cells.
  

Brenner Tumor

• 
  Uncommon
  
• 
  Epithelial component consists of nests of transitional cells resembling those lining the urinary bladder.
  
• 
  May be solid or cystic
  
• 
  Usually unilateral (approximately 90%)
  
• 
  Vary in size from small lesions <1cm to massive tumors up to 20-30 cm.
  
• 
  Majority of Brenner tumors are benign
  

Histology – Brenner Tumor

• 
  The histologic appearance of benign Brenner tumor is quite distinctive.
  

• 
  Variable numbers of nests of transitional epithelial cells with coffee bean-shaped nuclei scattered in a dense fibrous stroma.
  
• 
  Cell nests often become cystic containing eosinophilic debris or mucin.
  

Brenner Tumors

• 
  Gross section showing well circumscribed, yellow lobulated tumor
  
• 
  Low Power Histology
  
• 
  Showing nests of transitional epithelium in cellular fibrous stroma.
  

• 
  Nest containing microcysts, one filled with eosinophilic debris.
  
• 
  High power view showing the "coffee-bean" appearance of the nuclei
  

• 
  High power view showing Reinke's crystalloids.
  

Clinical Course of Surface Epithelial Tumors

• 
  All ovarian epithelial carcinomas produce similar clinical manifestations, most commonly lower abdominal pain and abdominal enlargement.
  
• 
  Gastrointestinal complaints, urinary frequency, dysuria, pelvic pressure, and many other symptoms may appear.
  
• 
  Benign lesions are easily resected with cure.
  
• 
  The malignant forms, however, tend to cause the progressive weakness, weight loss, and cachexia characteristic of all malignancies.
  

Surface epithelial ovarian cancer

• 
  Seen here is a laparotomy on a patient with intermittent small bowel obstruction.
  
• 
  A loop of small bowel (bottom of frame) is adherent to a poorly differentiated primary epithelial ovarian carcinoma (left of frame) that has spread to involve the pelvic sidewall, the bladder peritoneum, the serosa of the uterus, and the fallopian tube.
  

Clinical Course of Surface Epithelial Tumors (cont.)

• 
  If the carcinomas extend through the capsule of the tumor to seed the peritoneal cavity, massive ascites is common.
  
• 
  Characteristically, the ascitic fluid is filled with diagnostic exfoliated tumor cells.
  
• 
  The peritoneal seeding that these malignancies produce is quite distinctive:
  
• 
  They tend to seed all serosal surfaces diffusely with 0.1- to 0.5-cm nodules of tumor.
  
• 
  These surface implants rarely invade deeply into the underlying parenchyma of the organ.
  
• 
  The regional nodes are often involved, and metastases may be found in the liver, lungs, gastrointestinal tract, and elsewhere.
  
• 
  Because ovarian carcinomas often remain undiagnosed until very large, many patients are first seen with lesions that are no longer confined to the ovary.
  
• 
  This is perhaps the primary reason for the relatively poor 5- and 10-year survival rates for these patients, compared with rates in cervical and endometrial carcinoma.
  
• 
  For these reasons, specific biochemical markers for tumor antigens or tumor products in the plasma of these patients are used to identify them
  
• 
  One such marker is a high-molecular-weight glycoprotein present in more than 80% of serous and endometrioid carcinomas, known as CA-125
  

Surface epithelial ovarian cancer

• 
  Metastases from epithelial ovarian carcinoma
  

involving the omentum

Germ Cell Tumors

• 
  Constitute 15 to 20% of all ovarian tumors.
  
• 
  Majority (95%) are benign cystic teratomas (dermoid cysts)
  
• 
  Remainder tend to be malignant.
  

• 
  Unlike the malignant epithelial tumors, which usually occur during the sixth decade, this group of malignant tumors tends to occur mainly in children and young adults
  
• 
  Rare after menopause
  

• 
  Remarkable homology to germ tumors in the male testis and arise from germ cell differentiation in a similar manner
  
• 
  As a group, the tumors are characterized by
  

• 
  Rapid growth
  
• 
  Predilection for lymphatic and hematogenous spread
  
• 
  Predominantly unilateral development
  
• 
  Frequent mixtures of germ cell types
  
• 
  Associated with good prognosis.