Neoplasia_Block _08-34_

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    Department of Pathology and
       Laboratory Medicine


                  Edited By:
           Byron E. Crawford, M.D.
           Department of Pathology
           and Laboratory Medicine
      Tulane University School of Medicine
            New Orleans, Louisiana

              2005 – 2006
             Neoplasia Block

                                             TABLE OF CONTENTS

                                                NEOPLASIA BLOCK
Image Bank – Neoplasia .....................................................................................................4-7
Neoplasia, Part I..................................................................................................................8
Neoplasia, Part II ................................................................................................................9-10
Biology of the Neoplastic Cell ............................................................................................11-21
Molecular Basis of Neoplasia I ...........................................................................................22-37
Cancer Genetics ..................................................................................................................38-53
Viral and Immunological Aspeccts of Neoplasia .................................................................54-62
Molecular Aspects of Neoplasia II (Student Independent Study) .........................................63
Computer Lab – Bone Diseases Tumors only *Student Independent Student_.....................63
Soft Tissue Tumors.............................................................................................................64-84
Dermatopathology II – Neoplastic Diseases ........................................................................85-88
Neoplasia PBL – Case Study...............................................................................................89-90
Neoplasia Image Review.....................................................................................................91
Neoplasia Tutorial...............................................................................................................92-97
Computer Lab – Bone Diseases (Tumors Only) ..................................................................98
Neoplasia Image Review.....................................................................................................98
Dermatopathology II – Neoplastic Diseasess (Student Independent Study)..........................98
Exam II...............................................................................................................................99
CPC Grand Round ..............................................................................................................99


                                NEOPLASIA IMAGES


1. Lung-Hamartoma: A hamartoma is an abnormal proliferation of mature, disorganized cells or tissue
   inherent to that organ. In this example of a pulmonary hamartoma, bronchial epithelium, adipose tissue
   and cartilage are found in a disorganized proliferation. All of these tissues may be found in varying
   quantities in normal lung.

2. Lung-hamartoma: In this slide, the cartilage is more readily visible.

3. Monomorphic adenoma of the parotid gland: An adenoma is a benign neoplasm composed of epithelial
   cells forming benign glandular structures.

4. Gross picture of colon polyp: A polyp is a neoplasm which macroscopically projects above a mucosal
   surface. This term should only be applied to benign lesions. When malignant, the term “polypoid
   carcinoma” may be employed.

5. Squamous papilloma: A papilloma is a benign neoplasm composed of epithelial cells forming finger like

6. Higher power of squamous papilloma: A closer view of the finger like projections.

7. Cervix, squamous metaplasia: metaplasia is a REVERSIBLE change in which one mature cell type is
   replace with another. In this example, the columnar endocervical epithelium is being replaced by
   squamous epithelium.

8. Cervix, squamous metaplasia: In this higher power, the replacement of columnar epithelium by
   squamous epithelium is seen more easily.

9. Lung, bronchiolar metaplasia of alveoli: In this picture, the lining of the alveoli, which is comprised
   ordinarily by inconspicuous pneumocytes, is being replaced by columnar respiratory epithelium identical
   to that lining the bronchioles. This type of metaplasia occurs as a result of long standing chronic airway
   irritation, as with long term cigarette smoking. This particular example is very extreme.

10. Cervix, dysplasia: Dysplasia is defined as “disorderly but non-neoplastic growth” and is characterized by
    pleomorphism, hyperchromasia and loss of orientation. In this example the dysplastic squamous
    epithelium is observed on the right. Compare to normal squamous epithelium on the left. Dysplasia
    often precedes carcinoma and is thought of as “pre-malignant” in most cases. Mild dysplasias may be
    reversible and do not always progress to carcinoma

11. Cervix, dysplasia: In this example the dysplastic epithelium involves almost the entire thickness of the
    epithelium. Full thickness dysplasia is referred to as carcinoma in situ.


12. Hyperchromasia: Hyperchromasia refers to the dark staining nuclei which is usually due to increased
    DNA content. In this example of small cell carcinoma of the lung, all of the tumor cells exhibit darkly
   stained nuclei. Also note that the cells have very little cytoplasm. This is an example of increased
   nuclear/ cytoplasmic (N/C) ratio, another feature commonly seen in malignant cells. An increased
   mitotic count is also present.

13. Nuclear pleomorphism: nuclear pleomorphism refers to variation in the size and shape of the nuclei in
    comparison to their neighbors. In this example of a sarcoma, the nuclei vary greatly in size and shape.

14. Prominent nucleoli: In this example of large cell carcinoma of the lung, the malignant cells exhibit
    prominent nucleoli, a feature sometimes seen in malignant cells.

15. Mitotic figures: In this example of a sarcoma, an atypical (stickman) mitotic figure is present. Mitotic
    figures are often numerous in malignant processes and reflect increased proliferative activity.

16. Infiltrating pattern: Malignant tumors are generally not encapsulated and infiltrate tissue stroma. In this
    example of a malignant mesothelioma, the pleura is widely infiltrated by the malignant process and the
    tumor extends into adjacent fat. No normal tissue is present in this photograph.

17. Desmoplastic stromal response: As malignant tumors invade, they often induce fibrosis of the
    surrounding stroma, referred to as a desmoplastic response. In this example, nests of hyperchromatic
    tumor cells are inciting a surrounding desmoplastic response, represented by the grayish-blue stroma.

18. Perineural invasion: Malignant tumors often invade nerves and will grow within the perineural space.
    This example shows squamous cell carcinoma surrounding a nerve.

19. Vascular invasion: Malignant tumors often invade vascular or lymphatic channels. This is one method
    tumors may metastasize to lymph nodes or other organs. In this picture a nest of tumor cells is present
    within a blood vessel.

20. Metastasis: Metastasis is the single most important feature distinguishing benign from malignant tumors.
    In this example, metastatic tumor is present in a lymph node. Lymph node metastases often occur
    initially in the subcapsular sinus, as in this case.


21. Squamous cell carcinoma: A malignant tumor of epithelial cells is called a carcinoma. Squamous cell
    carcinoma is a comprised of malignant squamous cells. These tumors often show keratin pearl formation
    or intracellular bridges.

22. Squamous cell carcinoma: Note infiltrating pattern of malignant squamous cells with prominent nucleoli
    and keratinization. A desmoplastic stromal response is also evident.

23. Adenocarcinoma: A malignant tumor of glandular epithelium is called adenocarcinoma. In this example
    of colon carcinoma, malignant glands exhibiting hyperchromasia and an infiltrating pattern are seen on
    the left, while residual normal colon is seen on the right.

24. Adenocarcinoma: In this example of pulmonary adenocarcinoma, the malignant glands are fairly well
    differentiated, but are still readily distinguished from the surrounding normal lung.

25. Adenocarcinoma: Due to their derivation from glandular tissue, some adenocarcinomas produce
    abundant mucin. In this example, malignant tumor cells are seen to “float” in a sea of mucin. Tumors
    with this morphology are often designated as mucinous adenocarcinoma.

26. Adenocarcinoma: In some adenocarcinomas, the mucin is located intracellularly and displaces the
    nucleus to one side. Adenocarcinomas with this feature of often referred to as “signet ring”
    adenocarcinomas due to the morphology.

27. Basal Cell carcinoma: Basal cell carcinomas are a common skin malignancy arising from the basal cells
    of the epidermis. Note the nests of hyperchromatic, infiltrating tumor cells arising from the base of the

28. Lipoma: A benign tumor of adipose tissue is called a lipoma. A lipoma is comprised of mature adipose
    tissue and is typically encapsulated. A portion of the capsule is present on the left side of the picture.

29. Liposarcoma: Malignant tumors of mesenchymal origin are called sarcomas. A malignant tumor
    originating from adipose tissue is therefore called a liposarcoma. In this example of liposarcoma, there is
    a vague resemblance to adipose tissue, but there is greater cellular pleomorphism and the tumor is not

30. Liposarcoma: The key feature of a liposarcoma is the lipoblast, which is essentially an immature fat cell.
    The features of a lipoblast are multiple fat vacuoles which compress the nucleus, creating a scalloped

31. Leiomyoma: A benign tumor of smooth muscle is called a leiomyoma. Note the proliferation of uniform
    smooth muscle cells in this picture. There is little pleomorphism and no mitotic figures are present.

32. Leiomyosarcoma: A malignant tumor of smooth muscle origin is called a leiomyosarcoma. The tumor
    somewhat resembles the previous example of leiomyoma, yet there is greater pleomorphism and
    hyperchromasia and mitotic figures are numerous.

33. Osteosarcoma: Malignant tumors of bone origin are called osteosarcomas. In this picture, malignant
    cells are producing immature bone matrix referred to as “osteoid”, which is represented by the glassy,
    pink substance.

34. Carcinoid tumor: A carcinoid tumor is comprised of neuroendocrine cells and therefore may produce
    bioactive amines or peptides. These tumors generally behave in a low grade fashion, but may behave in
    an aggressive fashion. In this example, the carcinoid tumor is evidenced by cohesive nests of tumor cells
    located beneath the surface epithelium of the small intestine.

35. Teratoma: A teratoma is a tumor comprised of tissues from more than one germ cell layer, and is
    typically comprised of all three. The following pictures are from a benign mature teratoma of the ovary.
    This picture shows an area of glandular differentiation, representative of an epidermal component.

36. Teratoma: This picture from the same case demonstrates formation of a hair follicle.

37. Teratoma: This picture is from the same case as above. In this picture the tissue is neural, therefore
    representative of a mesenchymal component.


38. Lung carcinoma: In this photograph, the carcinoma is represented by the white area with yellowish
    discoloration. Note the irregular border, indicative of an infiltrative edge. The yellow areas are
    indicative of necrosis. Malignant tumors often contain areas of necrosis because their growth rate
    outpaces the vascular supply to the tumor.

39. Colon Carcinoma: Note the fungating tumor mass extending above the lumen of the colon. Such tumors
    often present with bowel obstruction.

40. Colon carcinoma: In this example, the tumor is ulcerated on the surface, a common finding in tumors
    exposed to an open lumen.

41. Teratoma: In this teratoma, adipose tissue is represented by the yellow areas. On the left side, a cavity is
    present which is lined by an epithelial derived covering. Such cavities are often filled with sebaceous
    material and hair. A few hairs are visible in this picture. Some teratomas contain grossly visible teeth.
42. Glioblastoma multiforme: Glial cells are a component of brain tissues, and malignant tumors of these
    cells have been traditionally called glioblastomas. “multiform” refers to the great cellular pleomorphism
    which is often present in the tumor. In this gross picture, the tumor has essentially replaced the entire left
    side of the cerebral cortex.

43. Lymphoma: Malignant tumors of lymphoid cells are called lymphomas. In spite of the nomenclature,
    lymphomas are always malignant. In this gross picture of a lymph node, the entire node is replaced by
    tumor which has a vaguely nodular appearance. The tumor has a firm consistency which is often referred
    to as “fish flesh”.

44. Sarcoma: Sarcomas often occur in the deep soft tissues. This is an example of a malignant tumor of
    skeletal muscle origin, therefore called rhabdomyosarcoma. Sarcomas are firm and have a fleshy
    appearance similar to that of lymphomas. In contrast, carcinomas tend to be of a much harder

                              August 29, 2005, 9:45– 10:45 a.m.
                                  Dr. William Robichaux

Topic: Neoplasia, Part I

Objectives, students should be able to do the following:

1).    Define, compare and contrast, and be able to discuss the terms atrophy, hypertrophy,
       hyperplasia, neoplasia and tumor.

2).    Define, compare and contrast, and be able to discuss the terms hamartoma, choristoma, and

3).    Define, compare and contrast, and be able to discuss hyperplasia, metaplasia, dysplasia,
       carcinoma in situ and invasive (infiltrating) carcinoma (including the term microinvasive

4).    Organize and be able to discuss the basic nomenclature of benign tumors and malignant tumors
       (carcinomas and sarcomas). Be able to list inappropriately named malignant tumors (i.e.
       nomenclature implies benign features but tumor is malignant).

5).    List and be able to discuss characteristics of a benign neoplasm and be able to define differentiate
       and characterized morphologically an adenoma, papilloma, polyp and cystadenoma.

6).    List and be able to discuss characteristics of malignant neoplasms including cytologic and
       architectural changes of malignant cells and cell groups, growth patterns, local invasive pattern
       and     metastatic patterns.

7).    Compare and contrast characteristics of benign and malignant neoplasms.

Vocabulary Words/Related Terms:

              Neoplasia                             Metaplasia
              Tumor                                 Carcinoma in situ
              Atrophy                               Microinvasive carcinoma
              Hypertrophy                           Carcinoma
              Hamartoma                             Sarcoma
              Choristoma/heterotopic rest           Anaplasia
              Teratoma                              Pleomorphism
              Adenoma                               Cribriform, gland within gland pattern
              Papilloma                             Tumor differentiation, well, moderate, poorly
              Polyp                                 Metastasis
              Cystadenoma                           Seeding
              Divergent differentiation             Lymphatic spread
              Hyperplasia                           Hematogenous spread

Recommended Reading: Robbins and Cotran Pathologic Basis of Disease by, Kumar, Abbas, Fausto,
                             Objective 1 - pp. 5-11, 270-272
                             Objective 2 – pp. 272
                             Objective 3 – p. 5-11, 277-276
                             Objective 4 - pp. 271-272

Objective 5 – pp. 270-271
Objective 6 - pp. 272-281
Objective 7 - pp. 270-280

                                                                                               Crawford, Byron E.

                            August 29, 2005, 11:00 a.m. – 12:00 noon
                                    Dr. William Robichaux

Topic: Neoplasia, Part II

Objectives, student should be able to:

1).    Analyze and be able to discuss the epidemiology of malignant neoplasms including incidence,
       geographic factors, environmental factors, age, genetic factors, carcinogens and changing incidence
       of carcinoma.

2).    List, compare and be able to discuss the different theories of origin of neoplasia (includes
       multifactorial theory, genetic mutations, viral oncogene, epigenetic theory, immune-surveillance
       dysfunction, monoclonal origin, and field origin).

3).    List, compare, differentiate and be able to discuss different categories of carcinogenic agents and
       their actions including chemical, radiation, viruses, nutritional, hormonal and genetic effects.

4).    Outline analyze and be able to discuss the biology-kinetics of tumor growth including mechanisms
       of progression, angiogenesis, and mechanisms of invasiveness and metastasis.

5).    Organize and be able to discuss structural and functional changes of neoplastic cells and
       precancerous or incipient malignant changes. Define and characterize occult malignancies and
       understand the kinetics of tumor growth.

6).    Organize, differentiate and be able to discuss the effects of neoplasia including local growth effects
       and effects of metastasis. Describe and be able to discuss the major paraneoplastic syndromes
       including associated malignancies and mechanisms (Table 7-12, Big Robbins).

7).    Organize and be able to discuss decision making processes when approaching a diagnosis of
       malignancy including clinical suspicions, definitive methods to diagnose (cytology, histology,
       frozen sections, special studies) biochemical and serological methods, and radiologic diagnosis. Be
       able to relate the important information provided by the pathologic diagnosis (tumor type, grade,
       degree of invasion - spread, and stage).

Vocabulary Words/Related Terms

       Immune surveillance dysfunction              Cachexia
       Carcinogen                                   Paraneoplastic syndromes [Cushing syndrome,
       Procarcinogen                                  inappropriate ADH, carcinoid, myasthenia
       Ultimate carcinogen                            gravis, hypertrophic osteoarthropathy,
       Promotors                                      venous thrombosis (trousseau’s phenomenon),
       Initiators                                     nonbacterial thrombotic endocarditis
       Tumor growth kinetics                          (marantic endocarditis)]
       Growth fraction                              Frozen section vs. paraffin section
       Doubling time                                Immunohistochemistry
       Tumor progression                            Fine needle aspiration, cytologic- pap smear
       Angiogenesis                                 Prostatic specific antigen (PSA)
       E-cadherins                                  Carcinoembryonic antigen (CEA)
       Metalloproteinases                           Alpha feto protein (AFP)
       Preneoplastic syndromes/precancerous         CA-125
Human chorionic gonadotrophin (HCG)

Neoplasia, Part II
Page 2

Recommended Reading: Robbins and Cotran Pathologic Basis of Disease by, Kumar, Abbas, Fausto,
                             Objective 1 - pp. 281-288
                             Objective 2 – Lecture, pp. 284-288, 293-298, 306-308,
                                            314-319, 331
                             Objective 3- pp. 319-328
                             Objective 4 - pp. 309-313
                             Objective 5 – Lecture, p. 275-279
                             Objective 6 - pp. 332-335
                             Objective 7 - pp. 335-339

                                                                                               Crawford, Byron E.

                               August 29, 2005, 1:00– 2:00 p.m.
                                   Dr. Krzysztof Moroz

Topic: Biology of the Neoplastic Cell

Objectives, the student should be able to:

1).    Outline the cell cycle and be able to discuss the significance of each phase, and factors that inhibit
       and activate the cycle.

2).    Organize and be able to discuss different mechanisms that control cell populations.

3).    Organize and be able to discuss characteristics of different cell types (labile, quiescent and
       permanent) giving examples of each, their proliferative potential and mechanisms that control their

4).    List, describe methods and be able to discuss different methods for determining cell
       proliferation rates.

5).    Define, and compare and contrast apoptosis and necrosis. Be able to discuss morphological
       features of apoptosis.

6).    List and be able to discuss functions of p53 and retinoblastoma gene. Be able to discuss the
       definitions of terms describing various DNA contents of neoplastic cells and their clinical

7).    Compare and contrast tumor grade and tumor stage.

Vocabulary Words/Related terms:

       Labile cells                          Apoptosis
       Quiescent cells                       Apoptotic bodies
       Permanent cells                       Karyorrhexis
       Ploidy                                Cytoplasmic blebbing
       Aneuploid                             Proliferation index
       Diploid                               Mitotic index
       p53                                   PCNA
       Retinoblastoma gene                   Feulgen reaction
       Transcription Factor E2F              Ki-67 nuclear antigen
       Cyclin                                flow cytometry
       Cyclin dependent kinase               Histopathologic tumor grade
       Tyrosine kinase                       TNM staging

Recommended Reading: Robbins and Cotran Pathologic Basis of Disease by, Kumar, Abbas, Fausto,
                       pp. 289-299, 299-306, 335

                                                                                               Crawford, Byron E.

                               August 30, 2005, 1:00 – 2:00 p.m.
                                      Dr. Gilbert Morris
                             Lecture and Student Independent Study

Topic: Molecular Basis of Neoplasia I

Objectives, the student should be able to do the following:

1).    Be able to differentiate and be able to discuss the differences between primary cells, immortal cells
       and transformed cells.

2).    List, differentiate and be able to discuss the major categories of oncogenes. Know the major proto-
       oncogenes, their method of activation and associated tumors.

3).    List, differentiate and be able to discuss the major categories of cancer suppressor genes, examples
       of each, mechanisms of tumor suppression, and tumors and syndromes associated with their

4).    Define apoptosis and be able to discuss the genes that promote and inhibit this process, and the
       affects of chemotherapy on tumors which loose their ability to induce apoptosis.

5).    Define and be able to discuss the role of DNA repair genes regarding carcinogenesis. Be able to
       discuss mechanisms of action of defective repair genes in hereditary nonpolyposis colon
              carcinoma, xeroderma pigmentosum and Bloom’s Syndrome, ataxia-telangectasia,
       Fanconi’s     Anemia.

6).    List and be able to discuss common types of chromosomal abnormalities which occur in
               tumor cells and give example of each. Be able to discuss the theory and supporting
       evidence that malignant tumors arise as a result of multiple events involving environmental
       factors, cancer suppressor genes, DNA repair genes, oncogenes and regulatory genes of apoptosis.

Vocabulary Words/Related Terms:

       Oncogenes                        Point mutation                            bcl-2/bax
       Proto-oncogene                   Chromosomal translocation                 Cyclin-dependent Kinases
       Antioncogene                     Cancer suppressor genes                   Telomerase
       Ras, myc, c-erb B-2              rb, BRCA-1, DCC                           Tyrosine Kinase
       Recessive oncogenes              Adenomatous polyposis coli gene
       Viral oncogenes                  p53
       Growth factors                   Apoptosis
       Growth factors receptors         Li Fraumeni Syndrome
       Signal transducing protein       DNA repair genes
       Nuclear regulatory protein       Balanced translocations
       Cyclins                          Deletions
       Gene amplification

Recommended reading: Robbins and Cotran Pathologic Basis of Disease by, Kumar, Abbas, Fausto,
                        pp. 289-299
                            August 31, 2005, 11:00 a.m. – 12:00 noon
                                      Kelly Jackson, M.S.

Topic: Cancer Genetics

Objectives, the student should be able to:

1).    Outline and be able to discuss the different genetic mechanisms that participate in the process of

2).    Organize and be able to discuss models of carcinogenesis including Knudson’s two-hit theory and
       Vogelstein’s’ model of colon carcinoma.

3).    Arrange and be able to discuss different hereditary preneoplastic conditions and benign hereditary
       neoplasms regarding chromosomal abnormalities, inheritance patterns and general phenotypic

4).    List and be able to discuss general features of hereditary malignancies including Retinoblastoma,
       Wilm’s tumor, familial adenomatous polyposis, hereditary non-polyposis colorectal cancer,
       hereditary breast cancer (1 and 2), ataxia telangectasia, Li Fraumeni syndrome and Cowden’s

5).    Organize and be able to discuss inherited immune deficiency syndromes, inheritance patterns and
       associated neoplasms.

Vocabulary Words/Related Terms:

              Tumor suppressor gene
              DNA repair gene
              Knudson’s two-hit theory
              Vogelstein’s model of colon cancer
              Lynch type I, II - Hereditary non-polyposis colon rectal cancer
              Ataxia - telangectasia
              Li-Fraumeni Syndrome
              Cowden Syndrome
              Familial adenomatous polyposis coli

Recommended Reading: Robbins and Cotran Pathologic Basis of Disease by, Kumar, Abbas, Fausto,
                       pp. 284-286, 302, 859, 861-862, 1134

                                                                                             Crawford, Byron E.

                              September 1, 2005, 8:30 – 9:30 a.m.
                                     Dr. Sanda Clejan

Topic: Viral and Immunological Aspects of Neoplasia

Objectives, the student should be able to do the following:

1)     Organize and be able to discuss the oncogenic effects of different RNA viruses including the
       acute transforming and slow transforming viruses. Understand the pathogenesis of these
       processes and be able to list the associated tumor with the different viruses.
2)     Organize and be able to discuss the oncogenic effects of different DNA viruses, including
       Human Papillomavirus (include different subtypes), Epstein Barr Virus, and Hepatitis B virus.
       Compare and contrast the pathogenesis of these viral oncogenic effects and be able to list
       associated tumors.
3)     Define, compare and contrast and be able to discuss tumor specific antigens and tumor
               associated antigens. Be able to categorize and list examples of each.
4)     Organize, compare and be able to discuss the different types of immune effector cells with anti-
       tumor activity. Be able to discuss their mechanisms of action.
5)     Organize, compare and be able to discuss the different types of escape mechanisms which
       cancers utilize to evade the immunosurveillance system of an immunocompetent patient.
6)     Compile, compare and be able to discuss the different approaches and mechanisms of
       immunotherapy in the treatment of malignancies.
7)     Determine the characteristics of an ideal tumor marker and the different types of tumor
               markers with examples of each.

Vocabulary Words/Related Terms

       Acute transforming virus                    Burkitt’s Lymphoma
       Slow transforming virus                     Nasopharyngeal carcinoma
       Insertional mutagenesis                     Hepatocellular carcinoma
       Human T cell leukemia virus                 Immunosurveillance
       Immortalization                             Tumor specific antigen
       Epstein Barr Virus (EBV)                    Tumor associated antigen
       Human Papillomavirus (HPV)                  Melanoma associated antigen-1
       Hepatitis B virus                           Natural killer cells
       X-protein                                   Cytokine therapy
       Squamous cell carcinoma of the cervix       Antibody based therapy
         and anogenital region                     Adaptive cellular therapy
       Condyloma acuminatum

Recommended Reading: Robbins and Cotran Pathologic Basis of Disease by, Kumar, Abbas, Fausto,
                        Objective 1 - pp. 327
                        Objective 2 - pp. 324-327
                        Objective 3- pp. 324-327
                        Objective 4 - pp. 330-332
                        Objective 5 – pp. 331.332
                        Objective 6 - Lecture
                        Objective 7 – Lecture

NEOPLASIA: Molecular Aspects of Neoplasia II
              August 31, 2005
              4:45 – 5:45 p.m.
        (Student Independent Study)
     See objectives on previous lecture:
  Molecular Basis of Neoplasia I (page 22)

      Computer Lab — Bone Diseases
               Tumors only
            September 1, 2005
             4:45 – 5:45 p.m.
       (Student Independent Study)
           Learning Module #12

                                                                                               Crawford, Byron E.

                              September 2, 2005, 8:30 – 9:30 a.m.
                                     Dr. Philip Daroca

Topic: Soft Tissue Tumors

Objectives, the student should be able to:

1).    Define what a soft tissue tumor is and organize a classification system of both benign and
       malignant types based on histogenesis.

2).    List and be able to discuss characteristics which differentiate benign soft tissue tumors from
       malignant ones.

3).    Outline and be able to discuss associated syndromes, environmental factors, genetic syndromes
       related to soft tissue tumors.

4).    Outline and be able to discuss the types of reactive pseudosarcomatous proliferations including
       clinical presentation, basic morphology and clinical course.

5).    Organize and be able to discuss clinical presentation of soft tissue tumors of fibrous
       differentiation, skeletal muscle differentiation, smooth muscle differentiation, vascular
       differentiation, fibrohistiocytic differentiation and lipocytic differentiation.

6).    List and be able to discuss clinical and morphological features of synovial sarcoma.

Vocabulary Words/Related Terms:

       Lipoma/Liposarcoma                           Embryonal rhabdomyosarcoma
       Nodular fasciitis                            Alveolar rhabdomyosarcoma
       Myositis ossificans                          Hemangioma
       Fibromatosis                                 Pyogenic granuloma
       Dupuytren contracture                        Bacillary angiomatosis
       Peyronie’s disease                           Angiosarcoma
       Desmoid tumor                                Kaposi’s sarcoma
       Fibrosarcoma                                 Hemangioendothelioma
       Dermatofibrosarcoma protuberans              Glomus tumor
       Malignant fibrous histiocytoma               Leiomyoma
       Rhabdomyosarcoma                             Leiomyosarcoma
       Botryoid sarcoma                             Synovial sarcoma
       Keloid                                       Giant cell tumor of tendon sheath
                                                    Pyogenic granuloma

Recommended Reading: Robbins and Cotran Pathologic Basis of Disease by, Kumar, Abbas, Fausto,
          ‘            pp. 1316-1323

                                                                                              Crawford, Byron E.

                              September 2, 2005, 9:45 – 10:45 a.m.
                                      Alun Wang, M.D.
                             Lecture and Student Independent Study

TOPIC: Dermatopathology II — Neoplastic diseases

Objectives, the student should be able to:

1).    Organize and be able to discuss Actinic keratosis, Basal cell carcinoma, squamous cell carcinoma,
       and keratoacanthoma in terms of etiology-pathogenesis, morphology, and clinical course.

2).    Organize and be able to discuss Melanocytic nevi in terms of definitions and types, clinical
       presentation, and morphology.

3).    Organize and discuss dysplastic nevi in terms of familial tendencies, pathogenesis, clinical
       presentation, morphology and clinical course.

4).    Organize and be able to discuss malignant melanoma in terms of different types, clinical
       presentation, morphology, and clinical course-prognosis.

5).    Organize and be able to discuss mycosis fungoides in terms of clinical presentation, morphology
       and clinical course.

6).    Define and be able to discuss general features of Merkel cell carcinoma, Acanthosis nigricans,
       fibrous histiocytoma, epidermal cysts, seborrheic keratosis, and adnexal skin tumors (skin
       appendage tumors).

Vocabulary Words/Related Terms - Define and be able to use in context:

              Actinic keratosis                                   Lentigo maligna
              Basal cell carcinoma                                Leukoplakia
              Basal cell nevus syndrome                           Malignant melanoma
              Blue nevus                                          Merkel cell carcinoma
              Breslow’s thickness of invasion                     Molluscum contagiosum
              Congenital nevus                                    Mycosis Fungoides
              Cutaneous T-cell lymphoma                           Pautrier microabscess
              Dermatofibroma                                      Seborrheic keratosis
              Dysplastic nevi                                     Sézary syndrome
              Epidermal cyst                                      Spitz nevus
              Keratoacanthoma                                     Squamous cell carcinoma

Recommended Reading: Robbins and Cotran Pathologic Basis of Disease by, Kumar, Abbas, Fausto,
                            Objective 1 – pp. 1239-1244
                            Objective 2 – pp. 1232
                            Objective 3 – pp. 1233-1234
                            Objective 4 – pp. 1234-1236

Objective 5 – pp. 1249-1250, 685
Objective 6 – pp. 1237-1239, 1244

                          NEOPLASIA PBL – Case Study
                           Clinical Case - Patient: BB
                               September 6, 2005
                                8:30 – 9:30 a.m.
                                Marc Kahn, M.D.

BB is a 58-year-old woman with an unremarkable past medical history who
notices a firm 2 cm lump in her right breast in the 3:00 position while showering.
She reports to her physician who confirms the presence of the mass. What other
questions are important to ask BB?

1.   How long has this been present?
2.   timing of menstrual cycle
3.   painful/painless
4.   menopausal status

What are risk factors for breast cancer that you would want to know about with
respect to this patient?

1.   nulliparity
2.   early menarche
3.   late first intercourse
4.   birth control pills may be protective
5.   late first pregnancy
6.   family history of breast, ovarian or possible prostate cancer

How would you proceed?

1. You could wait and follow this through a menstrual cycle or two
2. She will need a mammogram unless the mass completely disappears.

What could the mass represent?

1. fibrocystic disease
2. breast cancer

As the mass persists for two months, a mammogram is ordered that is read as
normal. What do you do now?

Even with a normal mammogram, a persistent palpable abnormality needs to be
biopsied. Failure to do this is one of the leading causes of malpractice
settlements in the US.

The patient undergoes a needle localization procedure. The needle biopsy
reveals infiltrating ductal carcinoma. What do you do now?

The mass needs to be excised and the axillary lymph nodes need to be assessed.
This can be done with axillary dissection or with sentinel node biopsy. This
procedure uses radiotracers to detect sentinel nodes and minimizes the number
of nodes that need to be sampled resulting in a decreased incidence of

What are the major determinants of breast cancer prognosis?

1. tumor size
   estrogen/progesterone receptor status
   number of positive axillary lymph nodes

What other information will help you determine tumor biology?

1.   her2-neu
2.   tumor grade
3.   S-phase
4.   ploidy

BB has a 3 cm tumor that is ER/PR positive. No axillary lymph nodes are positive
for tumor using sentinel lymph node mapping. She does not over express Her2-
neu, the tumor is diploid is intermediate grade and does not have an elevated S-
phase component.

What are your recommendations?

1. lumpectomy plus radiationis equivalent to mastectomy but NOT equivalent to
   lumpectomy alone. She therefore needs radiation.
2. chemotherapy in the adjuvant setting will also improve her survival
3. because her tumor is ER positive, she should receive adjuvant hormonal
   therapy with tamoxifen as well.

The patients 38-year-old daughter is concerned about her risk of breast cancer.
She has an aunt and two cousins in addition to her mother who have had
invasive breast cancer. Is there a role for prevention?

Likely yes. A large randomized trial has confirmed the efficacy of tamoxifen in
preventing breast cancers in patients at risk.

What are some genetic risk factors for breast cancer?

BRCA-1 and BRCA-2 are genes that are involved in DNA repair that increase the
risk of heritable breast cancer, ovarian cancer, and possibly prostate cancer.

The patient completes her therapy and does well for 4 years. She then begins to
notice back pain and is found to have recurrent disease invading her lumbar
vertebrae. What are her treatment options?

1.   further hormonal therapy
2.   additional chemotherapy
3.   radiation to the local lesions
4.   psychosocial support
5.   pain control
6.   pamidronate
7.   despite initial enthusiasm, bone marrow transplant is not superior to
     traditional chemotherapy

 Pathology Laboratory:
Neoplasia Image Review
   September 6, 2005
    1:00 – 2:00 p.m.
 Byron Crawford, M.D.

                                                                                                Crawford, Byron E.

                               September 6, 2005, 2:15 – 4:15 p.m.
                                       Tutorial Leader

Topic: Neoplasia Tutorial

Prior to the tutorial, review the three (3) case studies in the computer module titled “Neoplasia Cases”
and be able to answer questions to each. Answer questions to the neoplasia quiz at the end of the cases
and be prepared to turn the answers in at the beginning of the tutorial. Be prepared to discuss the three
cases and the “Neoplasia Quiz” at the tutorial.

Objectives, the student should be able to:

1).    Compare and contrast, and be able to discuss the definitions, and features of hyperplasia
       choristoma, hamartoma, adenoma, papilloma, and teratoma.

2).    Organize, be able to identify histologically, and be able to discuss the basic histologic features of

3).    Organize the features of , compare and contrast, and be able to differentiate squamous cell
       carcinoma vs. adenocarcinoma vs. carcinoid tumor vs. benign mesenchymal tumors vs. sarcoma
       vs. teratoma.

4).    Organize and be able to discuss the metaplasia-dysplasia-carcinoma in situ - invasive carcinoma
       sequence. Compare and contrast grading systems and staging of malignancies.

NOTE: Neoplasia Quiz Answers will be turned in at the beginning of the tutorial.

Recommended Reading: Robbins and Cotran Pathologic Basis of Disease by, Kumar, Abbas, Fausto,
                       Objective 1 - pp. 270-273, 6-11
                       Objective 2 - pp. 273-276
                       Objective 3 - image bank
                       Objective 4 - pp. 275-276, 335

                                       2005 - 2006
                                    NEOPLASIA QUIZ

1.   What feature is most important in differentiating a malignant from a benign tumor?

     A.        size
     B.        mitotic rate
     C.        metastasis
     D.        necrosis

2.   Cancers that commonly occur in tissues that have gone through the sequence of metaplasia
     dysplasia - malignancy include all except:

     A.        squamous cell carcinoma   of cervix
     B.        squamous cell carcinoma   of bladder
     C.        squamous cell carcinoma   of lung
     D.        squamous cell carcinoma   of esophagus

3.   A 65-year-old hypertensive male presented complaining of right costovertebral angle pain and
     gross hematuria. On physical examination a mass was palpated in the right flank. During the
     work-up for these problems, a solitary lesion was found in his right lung. Subsequently he had a
     trivial accident and fractured his right femur. Can you tie together the seemingly disparate
     findings in this case?

     A.        metastatic cancer
     B.        adenomas
     C.        neuroendocrine tumor
     D.        hamartomas

4.   A 79-year-old man was admitted to the hospital with complaint of suprapubic pain associated
     with hematuria. Workup for hematuria was pursued. Urine analysis showed numerous red blood
     cells, many neutrophils and bacteria. Urine cytology showed hyperchromatic neoplastic cells
     consistent with transitional cell carcinoma. Subsequent bladder biopsy showed a high grade
     transitional cell carcinoma.

     All of   the following statements about the above neoplasm are correct except:
     A.        It has been associated with p 53 gene mutation.
     B.        It arises only in the bladder.
     C.        It is regarded as clonal in nature
     D.        It has been etiologically associated with cigarette smoking.

5.   The process of grading and staging of cancer is an attempt to estimate the aggressiveness or degree
     of malignancy of a cancer. Which one of the following statements is correct?

     A.        Grading of cancer has greater clinical value.
     B.        Staging is based on the cytologic differentiation of tumor cells and the number of mitoses
               within the tumor.
     C.        Staging is based on the size of the primary lesion, its extent of spread to regional lymph
               nodes, and he presence or absence of metastases.
     D.        Grading is based on the degree of local invasion of the primary tumor.

6.   All of the following oncogenic viruses are correctly paired with associated tumors except:

     A.     HTLV-1 --Adult T cell leukemia/lymphoma
     B.     hepatitis C virus (HCV) -- hepatocellular carcinoma
     C.     human papilloma virus—laryngeal papillomas
     D.     Epstein -Barr virus—carcinoma of cervix.

7.   A 22-year-old female went for a routine visit to her gynecologist, who identified a well delimited
     mass in her right ovary. The left ovary felt enlarged, but did not show signs of a discrete mass.
     X-ray and cat scan were done to confirm the abnormality in the right ovary. The tumor was
     excised, grossly it was cystic and filled with greasy tan viscous jelly-like material containing hair.
     This tumor is best classified as:

     A.     teratoma (dermoid)
     B.     mixed tumor
     C.     carcinoma
     D.     sarcoma.

8.   A 62-year-old man complained of headaches for the past 5-6 months. Lately, the pain had become
     intolerable. He was vomiting frequently and complained of decreased visual acuity. Physical exam
     revealed the presence of papilledema. Following an MRI scan, which revealed a "butterfly" cerebral
     mass, craniotomy was preformed. The tissue was represented by irregularly arranged atypical glial
     cells which had markedly pleomorphic, hyperchromatic nuclei. Multi-lobulated nuclei with coarse
     irregular chromatin were also present along with prominent mitotic activity. There was palisading
     necrosis with angioplasia present. Based on the location, history, radiographic features and
     istology, this tumor is best represented as:

     A.     Malignant brain tumor (glioblastoma multiforme)
     B.     Benign
     C.     Metatastic carcinoma
     D.     Infarction
     E.     Low grade glioma

9.   This 75-year-old male went for a routine medical check-up. On digital rectal examination (DRE),
     an unusually hard nodule was palpated in the prostate gland. Blood was drawn in a red top tube,
     and serum sent for prostatic-specific antigen (PSA) showed a value of 80 ng/ml (expected, 0.1-4.0
     ng/ml). A biopsy was performed, followed by suprapubic prostatectomy. Which one of the
     following statements is not true?

     A.     Prostate specific antigen is a tumor marker commonly used to screen for prostate cancer.
     B.     The three most common cancers in men are prostate, lung and colorectum
     C.     There is 20% greater prevalence of cancer in African Americans.
     D.     Cancers that are decreasing in incidence are lung ,breast and prostate.
     E.     Risk factor for cancer include smoking, high fat, low fiber diet and obesity.

                  Name __________________________________   Box # __________

                       Neoplasia Quiz

                        Answer Sheet

1.   __________

2.   __________

3.   __________

4.   __________

5.   __________

6.   __________

7.   __________

8.   __________

9.   __________

                                         Neoplasia Cases
                               Salima Haque, MD, Sanda Clejan, PhD


This 67-year-old male complained of bright red blood in the stool, colicky abdominal pain and change in
bowel habit. He had an unintentional 10-pound weight loss.

       Investigations                              Results
       White blood cell count                      Normal
       ESR                                         Elevated
       Hemoglobin and Hematocrit                   Low
       Red blood cell                              Hypochromic,microcytic.
       Serum CEA                                   Markedly elevated
       Colonoscopy                                 Mass in the left colon.
       Biopsy of mass                              Malignant tumor of glandular epithelium.

      The patient was taken to surgery and a left hemicolectomy was performed. A large fungating mass
      was present in the left colon along with several smaller polypoid lesions. The polypoid lesions were
      diagnosed as dysplastic polyps. On further exploration a solitary metastatic nodule was found in
      the liver.


       1.     What is neoplasia? What is dysplasia?

       2.     What factors distinguish a malignant from a benign tumor?

       3.     What is a tumor marker? How is it used in the clinical setting?

       4.     What is grading and staging of cancer? What would be the correct stage in the case
              described above?


A 52-year-old female presented with increased vaginal bleeding, urinary frequency, a sensation of pelvic
discomfort, and dyspareunia. Following examination of a negative uterine curettage specimen, she
underwent abdominal hysterectomy.

       1.     Discuss the nomenclature of benign tumors.

       2.     Compare the properties of benign and malignant tumors.


This 65-year-old male had been a heavy smoker all of his life. He developed chronic bronchitis with
productive cough more than 20 years ago. He came to his doctor this time because of worsened cough and
increased purulent sputum sometimes tinged with blood. He had lost weight (15 lbs) and was
experiencing vague, continuous chest pain and dyspnea of recent onset (3 weeks).

A mass was detected in the right lung hilar region by X-ray. Atypical cells were identified by cytological
examination of the sputum and a bronchial lavage specimen. Bronchoscopy with biopsy showed the mass
to be malignant.The patient underwent lobectomy for removal of the malignant epithelial tumor.


       1.     What are malignant tumors of epithelial origin called? Discuss the nomenclature of
              malignant tumors.

       2.     What are the 3 main classes of carcinogenic agents? What are the chemical carcinogens that
              may induce malignant tumors of the lung?

       3.     What are paraneoplastic syndromes? Name the ones associated with lung cancer.

Neoplasia Quiz -

  Computer Lab — Bone Diseases
           Tumors only
        September 6, 2005
         4:45 – 5:45 p.m.
   (Student Independent Study)
       Learning Module #12

      Dr. Byron E. Crawford
        September 7, 2005
          5:00 – 6:00 p.m.

      Dermatopathology II
      Neoplastic Diseases
       September 8, 2005
        4:45 – 5:45 p.m.

(Student Independent Study)
      (see pages 85-88)

       EXAM II


8:00 A.M. – 1:00 P.M.

  **CPC Grand Round
   September 16, 2005
  12:00 noon – 1:00 p.m.
       Room 6001