General and Systemic Histopathology C601 and C602

Section 4 Neoplastic Disease

In this laboratory, we are looking at the differences between cells that exhibit normal cell growth and those that haveunregulated or altered growth. It's not the purpose to study the individual malignancies, rather the process and generalhistologic appearance. The term "neoplasia" does not necessarily imply malignancy. It simply means "new growth." Itapplies to both benign and malignant processes. When you have finished this laboratory, you should know what is meantby the terms: metaplasia, dysplasia and malignancy. In dealing with cytological aspects of malignant cells, we talk aboutthe nuclear/cytoplasmic ratio as well as nuclear hyperchromasia and angulation of the nuclear margins, nuclear molding aswell as the mitotic count. These are terms you will need to be familiar with. On the histologic level, you will encounterterms such as: gland within gland. Be sure you can define terms such as carcinoma, sarcoma and adenocarcinoma.

34General and Systemic Histopathology, Braun, C601/C602 Neoplastic Disease

Slide 21: Familial polyposis of the colon.The changes are subtle here. You really mustlook at the tissue on the slide before going tothe microscope. You will see little areas ofthickening of the mucosa and that's about it. In some areas there may even be a polypoidformation but the earliest changes are noteasy to see.

This slide shows the subtle changes in thebowel mucosa that can lead to big troubleslater. You will need to be on low power to initially identify the mucosal areas ofabnormality. Once you go to higher power,note the "branching" margins of the glands ofthe polyps and the "piling up" of theepithelium. You should have no troublefinding mitotic figures even though theselesions are benign. This congenital conditionoften leads to cancer of the colon later in life.Cancers of glandular origin are called adenocarcinomas, and frequently havehistologic patterns similar to the organ inwhich they arose. To reemphasize the point, however, what we are looking at here isbenign.

Your Observations

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Slide 32: Adenocarcinoma of rectum

Here the region of the tumor is prettyobvious. Look to see how it is spreading atthe lateral and deep margins. If we assume nonode or distant metastasis what would theDukes classification of this lesion be? Whatof the TMN classification?

This is a fairly high power view of the cancerwith normal tissue at the edges. On lowpower, you should be able to readily spot the different types of mucosa. In the area of thecancer, observe the "branching andarborizing" gland margins as well as the"gland within gland" pattern of themalignant cells. See what we mean by "nuclear atypia" of the epithelial cells. Theyare hyperchromatic with irregular nuclearstaining and "angulated" nuclear margins. Mitoses are every place. Note the spread intothe lamina propria of the malignant cells. Canyou think of conditions that are associatedwith an increased incidence of this condition?

Your Observations

36General and Systemic Histopathology, Braun, C601/C602 Neoplastic Disease

Slide 23: Metastatic transitional cell carcinomaNote how "meaty" the bone marrow space is. Much of the hematopoietic space has beenreplaced by scar tissue and tumor.

This slide shows metastatic "transitional cellcarcinoma" in the bone marrow. What are thesources of "transitional cell carcinoma?"First, try to get oriented by finding somebone spicules and hematopoietic tissue. Themalignant cells occur in clusters and closelyresemble malignant squamous cells.Although these cells don't look too wild, theyare not in the right place. Observe the"desmoplasia" (i.e. fibrosis) associated withthe groups of tumor cells.

Your Observations

37General and Systemic Histopathology, Braun, C601/C602 Neoplastic Disease

Slide 64: Squamous metaplasia of bronchial mucosa

The process of metaplasia is foundintermixed with the typical ciliated columnarepithelium. This is a reactive or adaptive process and not a true malignancy. What isthe definition of metaplasia?

This picture is of bronchial mucosa, showingthe reactive replacement of one type ofepithelium for another. It is technically not aneoplastic process, although continued injuryof the sort that lead to the metaplasia, canlead to dysplasia and possibly cancer. Herewe see respiratory epithelium being replacedby squamous. Smoking was the injury thatled to this alteration. Observe the inflammatory reaction beneath the mucosa.

Your Observations

38General and Systemic Histopathology, Braun, C601/C602 Neoplastic Disease

Slide 101: Squamous cell carcinoma of lungVery little alveolar lung is to be found on thisslide. The tumor has pretty much replacedeverything in the region of the sample. Note how the tumor surrounds and encases thefragments of bronchial cartilage.

This slide shows a typical squamous cellcarcinoma of the lung. Mitotic figures willbe common and some "tripolar" mitosesmight be present. You should be able to spotthe "intercellular bridges" (as opposed to theMadison County type) that characterize squamous cell malignancies. You will seegreat variation in size of cells and nuclei, butthe basics of malignant nuclear features areall here: nuclear/cytoplasmic ratio, angulatednuclear margins and nuclearhyperchromasia. The type of epithelium thatgave rise to this malignancy is not normallyfound in the lung, where do you think itcame from?

The insert shows a higher power view of thesquamous cell malignancy. The nuclearatypia and mitotic figures are pretty evident.

Your Observations

39General and Systemic Histopathology, Braun, C601/C602 Neoplastic Disease

Slide 116: Skin with malignant melanoma

Although this is just a little shave biopsy ofskin, you can easily see the central area ofthickening where the melanoma is.

The skin in this slide shows clusters ofmalignant melanocytes in the dermis.Observe the lack of "cohesion" of the cells.Nuclear features of malignancy should beobvious, and many cells will show abundantpigment. There is no "maturation fromsurface to base" in this lesion, an importantconsideration in distinguishing this from itsbenign counterpart, a "nevus." Depth ofpenetration is a critical part of "staging" thislesion.

A higher power view of one of the clusters ofmalignant melanocytes is seen in the insert.Here you can see the lack of cohesion of thecells and the rather marked degree of nuclearatypia.

Your Observations

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Slide 149: Pituitary adenoma

This gross photo of the brain with theadenoma was initially published inLaboratory Medicine, volume 29, number 10, 612. It had been submitted as one of thephotographs in the 1998 Art and Science ofMedicine Photography contest. It was takenand submitted by Dr. James M. Gulizia ofBrigham and Women's Hospital, Boston.

This picture is of a "benign" pituitaryadenoma. Although biologically benign, it issure in the wrong place and can be lethal justbecause of its location. You will see clustersand cords of the tumor cells, and it may betricky to distinguish the tumor from the surrounding normal pituitary. Does the term"tumor" apply here? You should see nomitoses.

Your Observations

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Slide 157: Skin with recurrent squamous cellcarcinoma

Here you see the groups of malignant cellswithin the dermis but seemingly having noconnection to the epidermis. What's the explanation?

The picture of this slide could be in focus alittle better, but it's what we have. Note theepithelium does not show changes of nuclearatypia nor cancer. The squamous cancer is inthe dermis, and represents a recurrence froma previously removed malignancy. On yourslide, you should be able to see the hallmark nuclear features of cancer i.e. angulatednuclear margins, hyperchromasia andreduced nuclear to cytoplasmic ratio. Lookfor "intracellular" bridges between themalignant cells.

Your Observations

42General and Systemic Histopathology, Braun, C601/C602 Neoplastic Disease

Slide 159: Teratoma of ovaryThis tissue just looks like little nondescriptstrips of tissue, but if you look far enoughyou may actually find a bit of ovarian tissueto help you get oriented. But, on the otherhand, maybe there's not any on your slide. Ifthat's the case, you'll just have to believe methat ovary is the origin. What you will seeare a great number of different tissue typeslining the cyst and within the cyst wall. I realize it may be a bit bewildering, but theseare fairly common benign tumors.

This is a rather peculiar, yet common andalmost always benign tumor of the ovary. Itoften has several "germ lines" present, givinga hodge-podge appearance of "mature" tissuetypes. This picture is from an area with prettyrepresentative benign colonic mucosa andbowel wall. You will likely find other tissuetypes in your slide. Be sure you cruise yourslide and are able to identify the ovariantissue from which this lesion arose.

Your Observations