PATHOLOGY / PATHOPHYSIOLOGY I

PATHOLOGY LABORATORY # 7

GENERAL

PATHOLOGY

HISTOPATHOLOGY WORKSHOP

HISTOPATHOLOGY WORKSHOP PAGE 1

INTRODUCTION

In this Histopathology Workshop session, pathological processes that were

discussed in the General Pathology course will be reviewed utilizing virtual microscopy
"slides" of histopathologic sections of a variety of specimens to provide some "firsthand" experience of how such sections are used toward the diagnosis of disease. The
virtual slides can be accessed via the Lablinks or DCDB sites.

We have selected the following eighteen (18) slides for their particular didactic
value at this stage of your training in Pathology. Corresponding photomicrographs are
provided to highlight the most significant alterations to be recognized during your
microscopic examination and, thus, to help you locate areas of particular pertinence
faster than you otherwise might.

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LIST OF SLIDES FOR THE HISTOPATHOLOGY WORKSHOP

SLIDE

ORGAN

DIAGNOSIS

#1

Appendix

Acute appendicitis

#2

Liver

Chronic passive congestion

#3

Lung

Pulmonary thromboembolism/infarct

#4

Lung

Pulmonary edema

#5

Aorta

Atherosclerosis

#6

Heart

Myocardial infarction

#7

Spleen & thyroid

Amyloidosis

#8

Skin

Chronic ulcer

#9

Intestine

Foreign body reaction

#10

Subcutis

Rheumatoid nodules

#11

Toe

Gout

#12

Uterus

Smooth muscle hypertrophy

#13

Liver

Cavernous hemangioma

#14

Lung

Adenocarcinoma

#15

Liver

Metastatic carcinoma (A)/sarcoma (B)

#16

Lymph node

Metastatic carcinoma

#17

Lung

Endolymphatic spread of carcinoma

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#1

APPENDIX:

ACUTE APPENDICITIS

The patient was an 18 year-old girl who presented with a history of rather diffuse
crampy abdominal pain, predominantly in the periumbilical area, that started 48 hours
prior to admission. Twenty-four hours prior to admission, the pain became more
intense, localized in the right lower quadrant and was accompanied by nausea. Her
temperature was 38.4oC, and her WBC was 14,800/l with a shift to the left. On
physical examination, there were guarding and tenderness in the right lower quadrant
with rebound tenderness and referred rebound tenderness to the right lower quadrant.
At laparotomy, the appendix was enlarged, intensely congested, and covered with a
dull, adherent, yellow-white film.
In examination of the cross-sectioned appendix, first review the normal histology
of the organ; from the lumen outward, identify the mucosa (where present), muscularis
mucosae, submucosa, muscularis propria and serosa. What is the nature of the
inflammatory infiltrate? Where are the inflammatory cells located? Are white blood cells
part of the normal architecture of the appendix and, if so, which category of cells would
they belong to? What about the architecture of the organ suggests a possible
pathogenesis of this disease?
[CORRESPONDING PHOTOMICROGRAPHS: #1 AND #2]

#2

LIVER:

CHRONIC PASSIVE CONGESTION

This tissue was taken at autopsy from a 72 year-old man with chronic right-sided
congestive heart failure. The liver weighed 2 kg (what is the normal weight?), and
sections showed a "nutmeg" pattern. In addition, there were ankle edema and pleural
effusions.
Microscopic examination of the liver at low power shows distension of the
sinusoids with RBCs. Is there any discernible pattern to this congestion? Where in the
hepatic lobule is it most marked? Why? Note the atrophy of hepatocytes in the most
congested areas. At high power, note the presence of pigment in the hepatocytes and
in Kupffer cells. What type of pigments may be present in the liver?
[CORRESPONDING PHOTOMICROGRAPHS: #3 AND #4]

#3

LUNG:

PULMONARY THROMBOEMBOLISM / INFARCTION

The two sections of tissue on the slide represent manifestations of a single

pathologic process. In one, medium to large pulmonary arteries contain early thrombi,

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showing layering of platelets and fibrin at the periphery, and centrally located RBCs; the
surrounding parenchyma is unremarkable or shows transudation of pink edema fluid
into the airspaces (see Slide #4). In the other, the airspaces are filled with fresh
hemorrhage. The alveolar septa are still identified in some areas, but obliterated in
others. How are the two samples of lung related pathogenetically? Which event
occurred first? Is either an inevitable sequel to the other? Do you expect either of these
events to occur in a previously healthy person?
[CORRESPONDING PHOTOMICROGRAPHS: #5 AND #6]

#4

LUNG:

PULMONARY EDEMA

Notice that the pulmonary capillaries are engorged with erythrocytes and the
alveolar lumina contain a pale eosinophilic precipitate. The large mononuclear cells in
the alveoli represent desquamated alveolar macrophages. While many of these cells
contain small amounts of very finely divided brown or black pigment, none of them
contain the typical masses of refractive golden brown pigment that is associated with
hemosiderin. The few cells, which do contain pigment that might be hemosiderin, are
principally interstitial in location. Does this observation contribute to an understanding
of the chronicity of the process? What would be most likely to cause the changes noted
in this slide? What would be the most likely clinical consequence of these changes?
[CORRESPONDING PHOTOMICROGRAPH: #7]

#5

AORTA:

ATHEROSCLEROSIS

Sections are from tissue removed at autopsy from a middle-aged patient who
presented with acute renal failure. Grossly, the thoracic and upper abdominal aorta
showed a cobblestoned yellow and brown but non-ulcerated intimal surface, while,
below the superior mesenteric artery, the abdominal aortic intima was brown, crusted,
flaky, and brittle. Microscopic sections are from the lower abdominal aorta. Identify the
media (is the aorta an elastic or a muscular artery?) and the adventitia. Note the
application of the atheromatous plaque to the intima. Can you identify the intimal
endothelium? The plaque consists of layers of amorphous, acellular eosinophilic
material, which may contain dissolved cholesterol crystals ("clefts", or empty needle-like
spaces) and areas of calcification. Some sections also show adherent thrombus, which
commonly complicates atherosclerosis in the aorta and other vessels. Can you suggest
a relationship between these findings in the aorta and the patient's clinical presentation? What might you expect to find in the kidneys?
[CORRESPONDING PHOTOMICROGRAPHS: #8 AND #9]

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#6

HEART:

MYOCARDIAL INFARCTION

In studying this section, first carefully identify the viable muscle fibers. Make note
of the appearance of the nuclei and the staining quality of the cytoplasm. Notice that
there are areas in the sections where the muscle fibers have completely lost their nuclei.
In some sections, a few fibers in the transitional zone will show faded (karyo-lytic)
nuclei or occasionally very dark (pyknotic) nuclei and, in some sections, fragmen-ted
(karyorrhectic) nuclei. Notice that the cytoplasm of the necrotic muscle fibers is for the
most part homogeneous and more intensely eosinophilic than that of the surroun-ding
viable muscle. Notice also that the cross striations of the cardiac muscle fibers have, for
the most part, disappeared. These changes may be summarized by the single
descriptive term "coagulation necrosis".
Note that the area of necrotic muscle is variably infiltrated by inflammatory cells,
mainly polymorphonuclear leukocytes, which in many areas show varying degrees of
degeneration. There is focal hemorrhage in some sections, and, in others, areas of
more or less mature scar tissue indicate previous episodes of necrosis.
[CORRESPONDING PHOTOMICROGRAPHS: #10 AND #11]

#7

SPLEEN and THYROID:

AMYLOIDOSIS

The patient was a 75 year-old man with a three-year history of prostatic

carcinoma and a two-year history of renal failure; he was also known to have atherosclerotic cardiovascular disease and ultimately died of a myocardial infarction. At
autopsy, many organs showed evidence of amyloid deposition, including the heart,
kidneys (hence the renal failure), liver, spleen, and gastrointestinal tract.
In the tissue on your slides, note the amorphous, bright pink material deposited in
the interstitium (area between the follicles) of the thyroid, and in the blood vessels and
parenchyma of the spleen. Immunofluorescent stains demonstrated both SAA and
amyloid P protein in the bright pink material. The more conventional Congo red stain
shows typical orange staining and, under polarized light, apple-green birefringence.
Can you explain the patient's clinical course based on the finding of amyloidosis? Into
which clinico-pathologic category of amyloidosis does this case fit?
[CORRESPONDING PHOTOMICROGRAPHS: #12 (SPLEEN) & #13 AND #14 (THYROID)]

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#8

SKIN:

CHRONIC ULCER

This section, taken from an ulcer on the leg of a patient with longstanding
diabetes mellitus, shows a chronic skin ulcer. Note the discontinuity of the epidermis,
which is the clinically apparent ulcer; the filling of the skin defect by a crust of fibrin and
cell debris (scab); and the underlying granulation tissue, which in the center of the lesion
is characterized by abundant capillaries, plump fibroblasts, and inflammatory cells.
Note that on the periphery of the granulation tissue, there is collagen deposition with
relatively few blood vessels: this is the result of organization of the lesion (scar).
[CORRESPONDING PHOTOMICROGRAPH: #15]

#9

INTESTINE:

FOREIGN BODY REACTION

This slide was prepared from tissue obtained at autopsy from a seven month-old
infant who had developed multiple complications of perinatal asphyxia. Surgery had
been done in early infancy to remove a necrotic segment of bowel; sections are from the
healed line of anastomosis. After noting the usual normal histologic landmarks, find the
foreign material (suture). What type of reaction is expected? How is it manifested in
this tissue? Note the many remaining giant cells in close proximity to the sutures:
Some show intracytoplasmic foreign matter, evidence of phagocytosis and attempted
removal. How would you predict this lesion to appear if years, rather than months, had
elapsed since the surgery (that is, how would the lesion ultimately organize)?
[CORRESPONDING PHOTOMICROGRAPH: #16]

#10

SUBCUTANEOUS TISSUE:

RHEUMATOID NODULES

Rheumatoid arthritis is a chronic systemic inflammatory disease, which may be

triggered by an exogenous microbial agent but is maintained by an autoimmune
process. Susceptible organ systems include skin, joints, muscles, heart, and lungs.
The sections provided are from surgically removed tissue from an affected patient who
had multiple nontender subcutaneous nodules. There are several well-circumscribed
granulomas characterized by a large central zone of fibrinoid necrosis, surrounded by a
rim of palisaded epithelioid histiocytes, lymphocytes, and plasma cells. In the appropriate clinical setting, this appearance is typical of rheumatoid nodules; however, if a
clinical history is not provided, what other granulomatous diseases should be ruled out,
and how is this done?
[CORRESPONDING PHOTOMICROGRAPH: #17]

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#11

TOE:

GOUT

This slide shows the pathologic deposition of urates, which appear as masses of
radiating, fine thread-like material in the tissues. These deposits occur as a result of
abnormalities in the nucleic acid metabolism. Notice that there is a very definite tissue
reaction to the deposited material. It is basically being treated as if it were a completely
foreign substance. Compare the reaction here to that in Slide #9.
[CORRESPONDING PHOTOMICROGRAPH: #18]

#12

UTERUS (GRAVID / NONGRAVID):

HYPERTROPHY

Each slide includes two sections of uterine wall (myometrium), one taken from a
pregnant (gravid) uterus at term and one from a nonpregnant uterus. During pregnancy, the uterus increases in size by a factor of 20, i.e., from an average of 75 grams to
1500 grams at term. This stupendous growth is accounted for mainly by hypertrophy of
the smooth muscle cells of the myometrium and to a much lesser extent by myometrial
hyperplasia. Evidence of the former process is seen by comparing the size of the
individual muscle fibers in the two tissue fragments: In the gravid uterus, the myometrial
cytoplasm is abundant and eosinophilic, and the nuclei are elongated and vesicular,
with occasional nucleoli. Mitoses indicating a concomitant increase in cell number
may also be seen. These features are absent in the nongravid uterus. Within three
weeks after delivery, the uterus undergoes an 85% reduction in size. This is due to a
reduction in cell size rather than in number.
[CORRESPONDING PHOTOMICROGRAPHS: #19 AND #20]

#13

LIVER:

CAVERNOUS HEMANGIOMA

This 0.5 cm nodule was discovered at autopsy in the liver of a patient with
unrelated medical problems. It is composed of dilated, anastomosing vascular channels
containing red blood cells; inconspicuous endothelium lines the channels. Is it a
neoplasm, and if so what kind? On what criteria do you base your diagnosis of
benignancy or malignancy?
Do you observe any abnormality in the surrounding liver (for extra credit)?
[CORRESPONDING PHOTOMICROGRAPH: #21]

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#14

LUNG:

ADENOCARCINOMA

This section shows a peripherally located nodule in the lung of a 62 year-old nonsmoker. Note, on low power, the relative circumscription of the tumor from the
surrounding tissue. It is composed of small nests and sheets of cells with a high
nuclear to cytoplasmic ratio, moderately pleomorphic nuclei, and prominent nucleoli;
there is essentially no recognizable tendency to form glands or acini. Note in the center
of the cell nests there are many dying and dead cells, characterized by pyknotic and
karyorrhectic nuclei; broad fields of pink-staining dead nuclei represent coagulative
necrosis.
The slide of metastatic carcinoma in the liver (#15) is from the same case.
[CORRESPONDING PHOTOMICROGRAPHS: #22 AND #23]

#15

LIVER:

METASTATIC CARCINOMA (A)/ SARCOMA (B)

Metastatic tumors are far commoner than primary tumors of the liver, which is a
very common target of metastasis for tumors originating in many other sites. Why?
Typically, multiple nodules are present. The commonest primary sites are breast, lung,
and colon. What is the usual route of spread of carcinomas and of sarcomas?
Approximately half of the slide sets contain a slide of liver with metastatic carcinoma
from the lung, and half show metastatic leiomyosarcoma. Compare the two types of
neoplasms, with respect to the location and the histologic appearance of the metastatic
nodules.
[CORRESPONDING PHOTOMICROGRAPHS: #24 (CARCINOMA) AND #25 (SARCOMA)]

#16

LYMPH NODE:

METASTATIC CARCINOMA

This slide is included to demonstrate the most common route of initial spread of
carcinomas, namely, via lymphatics. It is a section of an axillary lymph node contain-ing
a metastatic adenocarcinoma from the breast. Note the rim of normal lymph node (in
most areas represented only by the lymph node capsule); the carcinoma has completely replaced the lymphoid tissue. You can get a sense of how large the lymph node
is by looking at the slide with the naked eye: normal lymph nodes measure up to 1 cm.
Would this node have been palpable?
[CORRESPONDING PHOTOMICROGRAPH: #26]

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#17

LUNG:

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ENDOLYMPHATIC SPREAD OF CARCINOMA

This slide shows the tendency of some neoplasms to grow predominantly within
lymphatics. In soft tissue, this produces a characteristic indurated pattern, e.g.,
"inflammatory" carcinoma of the breast. In the lung, this growth pattern produces a
rather characteristic X-ray appearance and is associated with severe dyspnea and,
frequently, pulmonary hypertension. While almost any carcinoma may show endolymphatic growth in the lungs, carcinomas of the breast and of the stomach are more
likely to present this pattern of pulmonary metastasis.
[CORRESPONDING PHOTOMICROGRAPH: #27]

(09/11)