1. health and fitness
2. disease
3. cancer

,
MINNESOTA SOCIETY OF CLINICAL PATHOLOGISTS
ANNUAL SLIDE SEMINAR
NOVEMBER 10) 1984
DIAGNOSES AND COMMENTARIES
HENRY D. APPELMAN) MD
ANN ARBOR) MICHIGAN
1984 MSCP TUMOR SEMINAR
CLINICAL SUMMARIES
Case 1. A 22-year-old female noticed a mass in her right breast.
Attempted aspiration at home of what was clinically thought
to be a cyst resulted in a blood return . Biopsy of the
lesion was advised.
(Contributed by Dr. J. R. Goellner, Rochester, MN)
Case 2.
A 47-year-old female with recurrent dysfunctional bleeding
after two previous vacuum aspirat ions. Pelvic examination
was unremarkable. A hysterectomy was carried out. Gross
examination revealed a single 3.5 em myometrial nodule, located
submucosa11y,' and-having an appearance consistent with that of
()v ~ ~~
a leiomyoma.
(Contributed by ~. Minneapolis, MN)
Case 3. This 61-year- old man had a two month history of progressive
dysphagia and substernal pain accompanied by a 10 pound weight
loss. At the time of esophagoscopy , a·7 em in diameter intraluminal polyp was discovered .
(Contributed by Dr. H. D. Appelman , Ann Arbor, MI)
Case 4.
A 45-year-old man noted gross hematuria after strenuous exertion.
He was treated for presumed prostatitis without benefit and was
subsequently hospitalized for further evaluation. IVP demonstrated
delayed excretion on the left side, and suggested the presence
of an intrapelvic mass. Ultrasonography confirmed the presence
of a solid tumor within the left renal pelvis . At surgery a 3 em
polypoid firm tumor was found in this location. A left
nephroureterectomy was performed .
(Contributed by Dr. M. Wick, Minneapolis, MN)
Case 5.
A 68-year-old female had an anterior vaginal repair for prolapse.
Follow-up examination five weeks later showed a 1.5_cm nodule_
in the vaginal wall, at the area of the healing surgical scar.
The nodule had a hemorrhagic and ulcerated surface, ·and was
easily removed.
(Contributed by Dr. J . G. Ruggles, Watertown, SO)
Case 6.
\
~~h
A 63-year-old female complained of sudden onset of the left knee
pain. Roentgenographic examination showed enchondromatosis
involving the entire left femur with destructive changes in its
mid portion. Other bones showed changes consistent with multiple
enchondromatosis. The destructjve left femoral lesion was biopsied.
(Contributed by Dr. K. K. Unni ( Rochester, MN)
~
Case 7.
A 49-year-old female with recurrent mass in l eft lower leg
following two attempts at local excision. Because another
attempt at local resection was deemed impossible, a below the
knee amputation was performed. The tumor measured 10 x 5 x 4 em,
involved striated muscle and slightly eroded the tibia.
(Contributed by Or. H. R. Reiman, Rochester, MN)
Case 8.
A 78-year-old male complained of weakness . A left pleural
effusion of obscure etiology was found. Pleural stripping
revealed "markedly proliferative fibrous pleura" but the
surgeon indicated that the pleura was thickened and rather
hard . The patient deteriorated progressively and died of
cardiac arrest 8 months following thoracotomY.
(Contributed by Or. K. K. Unni, Rochester, MN)
Case 9. A 66-year-ol d woman complained of dyspnea and was found to have
an anterior mediastinal mass and reticulonodular infiltrate of
both lung fields , more pronounced in the upper lobes. Surgery
revealed a circumscribed spindle cell thymoma (6 x 6 x 5 em)
and patchy consolidation of lung. Sections are from the lung
sampling.
(Contributed by Dr. P. M. Banks, Rochester, MN)
Case 10.
This 43-year-old woman had an acute onset of severe periumbilical
cramping pain followed by signs of intestinal obstruction. In
the mid small intestine , the surgeon found a 4 em in diameter hard
mass extending into the l umen with central ulcer . Many of the
regional lymph nodes were enlarged.
(Contributed by Or. H. D. Appelman, Ann Arbor, MI)
Case 11. A 58-year- old man presented with ascites. Abdominal f l uid
cytology showed adenocarcinoma cells. A firm mass was palpated
at the upper pole of the right testis. Serum a-fetoprotein was
negative, a-subunit of human chorionic gonadotrophin was 400 IU.
An orchiectomy was performed for a tumor involving the spermatic
cord and adjacent epididymis and tunica albuginea.
(Contributed by Dr. G. M. Farrow, Rochester, MN)
Case 12. A 76-year-old female gave a history of squamous cell carcinoma
of the uterine cervix 30 years ago for which she was treated
with radiation therapy. Recently she complained of abdominal
pain and was found to have an enlarged uterus. A hysterectomy
was performed. The uterus weighed 120 grams and measured
13 x 6 x 5 em. It contained a polypoid papillary tumor in the
uterine cavity which measured 5 x 3 x 1 em.
(Contributed by Dr. Y. S. Leung , Bismarck, NO)
Case 13. A 62-year-old female was referred for evaluation of asymptomatic
hypercalcemia. Laboratory res~lts were as follows: Serum CA++ =
14. 4 mg/dL , P04 = 2. 3 mg/dL and Parathyroid Hormone = 150
(normal s 70 \li.Eq/ml ).
At cervica l exploration a 2.4 x 1.5 x 1.3 em
mass was found intimately related to the right lower pole of thyroid.
The mass was excis ed in continuity with the adjacent thyroid gland.
(Contributed by Dr. J. R. Goellner , Rochester, MN)
Case 14. This 23-year-old woman was asymptomatic. Her 40-year-old aunt,
however , died of disseminated colonic carcinoma. As a result,
the aunt's physician began to screen the entire family .for
colonic disease and discovered that several family members ,
including this woman , had adenomatosis coli.
(Contributed by Dr. H. D. Appelman, Ann Arbor, MI)
Case 15.
This 30-year-old man had 17 years of i ntermittent blood diarrhea
requiring three hospitalizations, during which the disease
appeared to respond to steroid therapy. The disease was
clinically more severe early , but for the past 10 years, except
for minor flares, he has had little problems with bowel function .
(Contributed by Dr. H. D. Appelman , Ann Arbor, MI)
Case 16.
This 73-year-old woman had noted progressive weakness and fatigue
over the past year. She appeared very pale. Her serum iron
was 31 micrograms per ml while her iron binding capacity was 389.
At gastroscopy , multiple polyps were found in the stomach , the
largest 3. 5 em in diameter. As a result , she underwent a partial
~astrectomy.
{Contributed by Dr. H. D. Appelman , Ann Arbor , MI)
Case 17. A 69-year-old female complained of rectal bleeding for 5 months.
On digital examination of the rectum, just inside the anal canal
and encompassing most of the circumference of the rectum, a hard,
fixed non-tender mass was present. Following biopsy, an
abdominoperineal resection was performed.
(Contributed by Dr. L. H. Weiland, Rochester, MN)
Case 18. A 53-year-old male had an anal lesion removed in November of 1983;
this was diagnosed as fibroepithelial polyp. The patient came
back for a follow-up in January of 1984 , at which time an elevated
thickened region of anal mucosa was noted. This lesion was excised.
(Contributed by Dr. G. Osteraas, Li ttle Falls, MN)
Case 19. A 61-year-old female presented with acute abdominal pai n. X-rays
showed a nonreducible small bowel intussusception. Laparotomy. -·
was performed, and a segmental resection of the ileum was carried
out. Gross examination showed that the head of the intussusception
was formed by a pedunculated intraluminal mass measuring 5 em in
diameter, 7 em in length , with a stalk which measured 1.5 em at the
base. The mass was solid, of elastic consistency and ulcerated.
(Contributed by Dr. M. Stanley, Minneapolis, MN)
Case 20 . A 65-year-old female had surgery for cholecystoduodenal fistula.
At laparotomy, the findings were acute and chronic cholecystiti.s ,
cholecystoduodenal fistula and gallstone ileus. In addition, a
single liver mass was found and ~ partial hepatectomy was performed.
The specimen measured 10 x 7 em.! It had a well defined tumor at
its periphery measuring 7.5 x 5.5 x 7 em. The tumor was solid,
light yellow, bosselated, and of firm consistency. The cut surface
was smooth and light greyish brown.
(contributed by Dr. L. Lu, Winnipeg, Manitoba, Canada)
Case
Identification
Contributor
2-944-267
Dr. J. R. Goellner
Rochester, MN
R84/935
z
Minneapolis , MN
Dr. H. Appelman
Ann Arbor, MI
Dr. M. Wick
Minneapolis, MN
Dr. J. G. Ruggles
Watertown, SO
Dr. K. K. Unni
Rochester, MN
Dr. H. R. Reiman
Rochester, MN
Dr. K. K. Unni
Rochester, MN
Dr. P. M. Banks
Rochester, MN
Dr. H. Appelman
Ann Arbor, MI
Dr. G. M. Farrow
Rochester, MN
Dr. Y. S. Leung
Bismarck, NO
Dr. J. R. Goellner
Rochester , MN
Dr. H. Appelman
Ann Arbor , MI
Dr. H. Appelman
Ann Arbor, MI
Dr. H. Appelman
Ann Arbor, MI
Dr. L. H. Weiland
Rochester, MN
Dr. G. Osteraas
Little Falls, MN
Dr. M. Stanley
Minneapolis, MN I
Dr. L. Lu
Winnipeg, Manitoba
8879-LCJ
UH83-4961
R84-846
3-350-867
3-575-812
1250Y78
3-667-003
7341-CJ
11
OSS-84-294
12
R82- 859
13
3-730-295
14
12000-CJ
15
2323-CJ
16
1579-LCJ
17
3-726-853
18
R84-202
19
R84-221
20
R84-1036
~"' ~~
D¥"v Z II
Fh'u
Location/
Contributor's Diagnosis
Breast/
Malig. fibrous histiocytoma , giant cell
variant
Uterus/
Bizarre leiomyoma ~
Esophagus/
Pseudosa rcorna ?
Renal pelvis/
Sarcomatoid transitional cell garcinoma
Vagina/
Pseudosarcoma <;
Femur/ ·
{
Dedifferentiated chondrosarcoma
Leg/
t
Myxoid chondrosarcoma
Pleura/
~
Diffuse fibrolfs mesothel ioma Lung/
,
Malignant lymphoma ~
Small Intestine/
Ininunoblastic sarcoma .. l--c,,
Para testis/
Gr. 3 adenocarcinoma, primary site? ')
Uterus/
Papillary carcinoma 1 <
Parathyroid/
Carcinoma
Colon/
Adenoma-carcinoma transformation 1 4
Colon/
Ulcerative colitis with dysplasia "f
Stomach/
Polyps
1c
Rectum/
Cl oacogeni c carcinoma 1
Anus/
Verrucous carcinoma ' ~ ,
11 eum/
Inflammatory fibroid polyp
Liver/
Clear cell hepatoma
2 ~
t
Case 1
Diagnosis:
Breast; malignant
sub type),
unless
carcinoma.
fibrous hi stiocytoma (giant cell
other
sections
con ta in
invasive
This breast ma ss in a twenty-two year old woman contains a central
hemorrhagic cavity with a surrounding proliferation of variable
morphologic features.
Some a reas are densely c ellular and contain a
mixture of small plump cells,
osteoclast-like gia nt cells, and
pleomorphic cells.
In general, the mitotic rate is low, although
occasional mitoses, some quite atypical , are present. Other areas are
more heavily collagenized, and there is even a single fo cus in which
spindle cells are arranged in a vaguely storiform pattern. The cells
and accompanying stroma extend into the adipose tissue and between
breast ducts.
1'he differential diagnosis includes nothing conunon.
On cursory
exami na tion, there are some features which suggest that this lesion
may be reactive, including the central hemorrhage , the abundant
hemosiderin in many of the proliferating cells, the puny mitotic ra te,
the abundance o f
benign appea r ing giant cells,
the peripheral
collageniza t i on, and the peripheral sclerotic vasculature.
however,
the infiltrating appearance and the bizarre mitoses a s well as the
extreme pleomorphism o f many of the cells indi ca t e that this is
ma lignant . Th e t wo possibilities now include a sarcoma or a carcinoma
with sarcomatous me taplasia.
Since this slide contains only the
stromal elements, we will assume that this is all that there is, so
that a diagnosis of sarcoma can be made.
The combination of cellular
characteristics place this i n the category of malignan t fibrou s
histi ocytoma.
In this case, this is a most unusua l tumor because it
is occurring in t he breast or subcutis of chest wall, an uncommon site
The current data suggests that
and in an unusually young patient.
only about 1% of MFH would occur with this combination.
The breast MFH literature is so limited, that extensive analysis is
not worthwhile.
Reference 3 below conta ins anything anybody needs to
know, i f not more.
References
1.
Bauer, T. W., et al:
spindle cell ca rc inoma of the breast: Four
cases and review of the literature. Hum Patho1 15: 147-152 , 1984.
2.
Kaufman,
H.
W.,
et
al:
pseudosa rc oma tous metap l a sia.
3.
Langham, M. R., Jr., et al:
Ma lignant fib rous histiocytoma o f
the breast : a case report and review of the literature.
Cancer
54:558-563, 1984.
4.
Norris,
H. J. ,
and Taylor, H.
B.:
Sarcomas and
mesenchymal tumors o f the breast. Ca ncer 22:22-28, 1968.
1510198407
Carcinoma
of
the
breast
Cancer 53:1908- 1917, 1984.
with
re lated
CASE 2
Diagnosis:
Myometrium; bizarre leiomyoma.
This is a myometrial mass which looked grossly like a leiomyoma.
However, microscopically it does not look anything like a leiomyoma.
It is composed of extremely pleomorphic cells with abundant fibrillar
eosinophilic cytoplasm, but the mitotic count is l ow (1 per 10 high
power field, or with my microscope, 1 per 1.57 square mm). Follow-up
data on such lesions i nd icate that they run a totally benign course in
spite of their cytologic bizarre appearance.
This is an example of something that looks bad but isn't, and this case
raises the issue of predictive factors of malignancy in stromal tumors.
For uterine stromal tumors, the best predictor of malignant behavior
appears to be the mitotic rate as measured in numbers of mitoses per a
given number of high power fields, usually 10.
In some studies, the
magic number of mitoses is 5 or more per 10 high power fields, while in
other studies that number is 10 mitoses per 10 high power fields. Of
course, counting mitoses is fraught with difficulties, including the
size of the field counted, the fastidiousness of the observer, and the
reproducibility.
The tumor in this case is one of a number of unusual varients of
uterine smooth muscle tumors which include bizarre leiomyomas, epithelioid leiomyomas, palisaded leiomyomas, and leiomyosarcomas.
References
1.
Burns, B., et al: Morphologic features of prognostic significance
in uterine smooth muscle tumors: A review of eighty-four cases.
Am J Obstet Gynecol 135:109, 1979.
2.
Christopherson, W. H. and Richardson, H. :
Uterine mesenchymal
tumors. Pathology Annual 16(1):215-245, 1981.
3.
Hart, W. R., and Billman, J. K., Jr.:
A reassessment of uterine
neoplasms originally diagnosed as leiomyosarcomas. Cancer 41:19021910, 1978 .
4.
Kurman, R. J., and Norris, H. J.:
Mesenchyma l tumors of the
uterus: VI.
Epithelioid smooth muscle tumors i n cluding leiomyoblastoma and clear-cell leiomyoma, a clinical and pathologic
analysis of 26 cases. Cancer 37:1853-1865, 1976.
Case 3
Diagnosis:
Esophagus, pseudosarcomatous squamous cell carcinoma
(polypoid carcinoma, spindled carcinoma, carci.n osarcoma,
or any other name you prefer).
Most of the sections of this large bulky, fairly well circumscribed
esophageal mass indicate that it is composed of some kind of cellular
sarcomatous tissue with a variety of patterns, includ ing scattered
areas which resemble MFR. Additional sections from the margin indicate
that there is also a component of squamous cell carcinoma of various
degrees of differentiat ion and of various patterns. This tumor goes by
all of the names listed above and probably additional names as well.
It seems to be a peculiar form of carcinoma, usually squamous cell, in
which the invading carcinoma cells seem to loose their epithelial
characteristics and undergo metamorphosis or metaplasia into stromal
cells resembling fibroblasts.
Thus, in reality, at the height of
stromal metaplasia, the lesion becomes an honest-to-goodness carcinosarcoma.
Tumors of similar type have now been reported virtually
everywhere in the body, most notably in the upper respiratory tract and
esophagus , but there are recent reports of similar tumors in the
breast, female genital tract, and gallbladder.
The peculiar thing
about these tumors is that i n spite of their bizarre cytologic appearance, they can remain at a fairly low stage even while growing to
considerable bulk.
This probably accounts for their relatively good
prognosis compared with ordinary carcinomas arising in similar sites.
However, this rule is not uniform for al l sites in which such tumors
arise.
References
1.
Appelman, H. D.:
Stromal tumors of the esophagus, stomach and
duodenum, chapter 7 in Appelman, H. D. (Ed): Pathology of the
Esophagus, Stomach and Duodenum, Churchill Livingstone, New York,
1984.
2.
Enterline, H. and Thompson, J.:
Chapter 8
Esophagus, Springer-Verlag, New York, 1984.
3.
The most recent case report: Hanada, 11. et al:
Carcinosarcoma
of the esophagus with osseous and cartilaginous production: a
combined study of keratin immunohistochemistry and electron
microscopy. Acta Pathol Jpn 34:669-678, 1984.
i n Pathology of the
Case 4
Diagnosis:
Renal pelvis:
carcinoma.
spindled
transitional
cell
(urothelial)
Although t .h is was described grossly as a polypoid tumor, the microscopic sections contain instead a plaque of invasive spindle cell
malignancy which extends into the muscularis, but not through it.
In
some sections, at one of the margins, the transitional epithelium is
hyperplastic with as many as 17 cell layers. This hyperplasia gradually
gives way to increasing dysplasia with mild nuclear pleomorphism,
mitotic figures, and eventually a high NC ratio.
The spindle cell
tumor is intimately attached to this epithelium, and it is pos.s ible to
imagine all kinds of transitions from one to the other. In fa •c t, such
transitions may actually even occur.
Certainly, the spindled variety
of urothelial carcinoma is one of the types known to occur, although it
is uncommon.
In this case, as in some of the preceding cases, the
problem is determining whether the spindled cells are really spindled
carcinoma cells or spindled stromal cells .
The solution to this
problem would depend upon the use of either ultrastructural analysis,
cell marker immunohistochemistry, or both.
Preliminary histochemical
.,
studies for carcinoembryonic antigen, keratin, and epithelial membrane
antigen fail to demonstrate any epithelial characteristics in the
stromal cells.
However, because of the urothelial dysplasia at the
margin, i t is probably not worth fighting the diagnosis of spindled
carcinoma.
Peculiarly, the pattern of urothelial dysplasia at the
margin is unusual.
In the present case, it is flat, rather than
papillary.
Usually such dysplastic changes comb ined with this degree
of hyperplasia will occur in papillary lesions. At the same time, the
typical flat urothelial dysplasias most commonly associated with
invasive carcinomas tend to be less hyperplastic and more pleomorphic
with a much greater degree of nuclear abnormality.
References
As best as I can tell, there are no pertinent references which apply
specifically to this type of a case. However, for completeness, the
latest reference on tumors of the upper urinary tract is by Pettersson,
S., et al: Treatment of urothelial tumors of the upper urinary tract
by nephroureterectomy, renal auto transplantation, and pylocystostomy.
Cancer 54:379-386, 1984.
Case 5
Diagnosis:
Vagina,
postoperative
(pseudosarcoma).
spindle
cell
nodule
This small lump popped up in the developing scar five weeks after a
vaginal repair.
It is composed of a highly vascular spindle cell
proliferation with a high mitotic rate, but a picture of cellular
uniformity .
It appears to be a granulation tissue which has gone
bananas.
Although the cells are dividing like crazy, the clinical
setting and the rapidity of its development indicate that it is a
reactive les ion.
Reference
Proppe, K. H., et al:
Postoperative spindle cell nodules of genitourinary tract resembling sarcomas: A report of eight c a ses. Am J Surg
Path ol 8:101- 108, 1984.
Case 6
Diagnosis:
Femur: dedifferentiated chondrosarcoma 1n a patient with
multiple enchondromatosis
This case has a mixture of n odules of well differentiated cartilaginous
tumor and spindle cell sarcoma which undergoes varying degrees of
collagenization and which invades host bone.
This dichotomy is the
characteristic combination needed for the above diagno&is. The aggressive sarcomatous component, which can be either fibro-, oesto-, or MFH,
dictates the behavior of these lesions.
Also, a biopsy of a large
carti laginous tumor may not uncover the more aggressive sarcomatous
component.
Reference
1.
Dahlin, D. C.:
Bone Tumors: General Aspects and Data oo 6,221
Cases. Page 205-206, Charles C. Thomas, Springfield, 1978.
2.
Jaworski, R.C.:
Dedifferentiated chondrosarcoma:
tural study. Cancer 53:2674-2678, 1984.
3.
McCarthy, E. F. and Dorfman, H. D.:
Chondrosarcoma of bone witb
dedifferentiation: a study of eighteen cases. Hum Pathol 13:36-40,
1982.
an ultrastruc-
Case 7
Diagnosis:
Soft t issue of leg; myxoid chondrosarcoma.
These are samples from a large recurrent soft tissue mass in the lower
leg.
Diagnosis depends purely on pattern recognition.
This tumor is
defined by all who know and love it as a chondrosarcoma, yet it has
absolutely no features of differentiated chondrosarcoma.
The .P attern
has been likened to the early stages of fetal cartilage development.
The background of a prominent myxoid matrix containing clusters and
interconnecting cords of small dark cells with little cytoplasm is
characteristic.
Some areas resemble mucinous carcinoma, some look a
bit like yolk sac carcinoma, and other foci are much like areas in
pleomorphic adenomas of salivary gland or the comparable tumors of
sweat glands.
This is the same neoplasm which has been designated in
some stud ies as "chordoid sarcoma".
The mucinous matrix contains
sulfated mucopolysaccharides of the type found in mature cartilage.
This is one of a vast array of muci nous tumors found in soft tissue,
all of which have their characteristic cellular and architectural
features and mucin tyPes.
It appears that almost every soft tissue
tumor can develop a prominent or even dominant mucinous component. The
reference by Allen, below, is an excellent discussion of the differential diagnosis of soft tissue mucinous tumors.
This tumor is also an excellent example of how immunohistochemistry
for ce r ta in cell markers can b e o f diagnostic assista nce. I n the present case, the cells stain i ntensely with the S-100 protein antibody.
Initially, this was thought to be a marker of cells of neural origin,
including Schwenn cells, but now, we are finding that it has more widespread use, and stains cartilage cells and adipose cells as well.
References
1.
Allen, P. W.:
Myxoid tumors of soft tissue.
(1):133-192, 1980.
Pathology Annual 15
2.
Enzinger, F.M. and Shiraki, H.: Extra skeletal myxoid chondrosarcoma: an analysis of thi r ty fou r cases. Hum Pathol 3:421-4 35, 1972.
3.
Fu, Y-S, and Kay, S.:
A comparative ultras tructural study of
Cancer
mesenchymal chondrosarcoma and myxoid chondrosarcoma.
33:1531-1542, 1974.
4.
Nakamura, Y., et al:
S-100 protein in tumors of cartilage and
bone, an inununohistochemical study.
Cancer 52:1820-1824, 1983.
Case 8
Diagnos is:
Pleura; d iffuse malignant mesothelioma (sarcomatoid and
desmoplastic mixture, for the puri sts).
These are sections from the pleural tumor from the autop s y.
Some
actually contain lung a nd hea r t, connected by the proliferation in
question.
The pleura is massively thic kened by a spindle cell proliferation and asso ciated dense collagenization . Actually , th e collagen
is far more impressiv e than the c e llula rity .
Nevertheless, there are
some cellular fo ci i n which mitotic figures are easily found and whi ch
could pass fo r some type of low grade sarcoma.
Suc h cellular foci
merge g radua lly with progressively mo re collagenized areas c ulmina ting
in virtually acellular collagen which has a peculiar woven appearance.
At t .h e periphery, the mixture o f spi n dle cells and collagen i nvades the
surrounding t issues, including c ardiac muscle and lung.
This is
r eadily c lassifiable as a form of dif fuse ma lignant mesothelioma, and
there are e nough forms and enough names for them to drive many studious
pathologists to drink. This nightmare of n omenclature bas been admirab ly analyzed in the paper by Adams and Unni below.
Al though variable numbers of cases of diffuse malignant mesothel ioma
are associated wit h asb estos exposure, an equally large number, or perha ps even a greater number, are no t .
The recent study by Pete rson,
et al, analyze.s possibilities of other types of exposure in the genesis
of these tumors.
Refe r ences
l.
Adams , V. I., and Unni, K. K.: Diffuse malignant mesothelioma of
pleura: diagnostic criteria based on an autopsy study. Am J Cli n
Pathol 82 :15-23 , 1984 .
2.
Bolen , J . W., and Thorning, D.:
Mesotheliomas: a ligh t and
electron microscopical study concerning h is togenetic relationships
between the epithelial and the mesenchymal va riants . Am J Surg
Pathol 4:451-464, 1980.
3.
Cantin, R., et al :
Desmoplastic diffuse mesothelioma.
Pathol 6:215 •222, 1982.
4.
Kanne rste i n, M., and Churg, J.:
Desmopla stic diffuse malignant
mesothelioma.
Chapte r 2 in Progress in Surgical Pathology, vol .
2, Fenoglio, C. M. a nd Wolff, M. (Eds) , Masson Publishing, Ne w
York, 1980.
5.
Peterson, J. T. , Jr. ,
mes othe lioma : a review.
6.
Wanebo,
1976.
H.
et al:
Non-asbestos rel ated
Cancer 54:951-960, 1984 .
Am J Surg
malignant
J., et al: Pleural mesothelioma. Cancer 38:2481-2488,
7.
Whitaker, D. and Shilkan, K. B.:
Diagnosis of pleural malignant
mesothelioma in life - a practical approach. J Pathol 143:147-
175, 1984.
Case 9
Diagnosis:
Lung;
malignant lymphoma of some small cell category.
The pulmonary parenchyma is strikingly altered by an infiltrate of
lymphoid cells which has several patterns. It infiltrates the alveolar
walls and septa.
It surrounds and invades small bronchi and vessels.
It also forms fa irly solid masses with the cells apparently filling
some air spaces.
The lymphoid cells, in general, are round with
rounded nuclei, a hint of plasmacytoid differentiation, and scattered
mitoses.
The differential diagnosis involves all lymphoid infiltrates in lung,
such as lymphoid interstitial pneumonia, the so-called pulmonary
pseudolymphoma,
lymphomatoid granulomatosis,
and lymphomas.
Some
recent studies, particularly those by C6lby and Carrington, suggest
that the distinction among these various entities may be quite muddied,
so that almost any lymphoid infiltrate of lung might be suspect for
lymphoma. Fortunately, for most of us, such lymphoid pulmonary lesions
are uncommon, and there are a select cadre of experts, probably readily
available for consultation.
References
1.
Colby, T. V., and Carrington, C. B.:
Lymphoreticular numors and
infiltrates of the lung .
Pathology Annual 18(1):27-70, 1983.
2.
Colby, T.V., and Carrington, C. B.: Pulmonary lymphomas simulating lymphomatoid granulomatosis.
Am J Surg Pathol 6:19-32, 1982.
3.
Colby, T.V., and Carrington, C. B.: Pulmonary lymphomas: cur rent
concepts . Hum Pathol 14:884-887, 1983 .
4.
Garrison,
lymphoma.
5.
Koss, M. N. , et al:
Primary non-Hodgkin 1 s lymphoma and pseudolymphoma of lung: a study of 161 patients.
Hum Pathol 14:1024-
C. 0., et al:
The alveolar pattern
Mayo Clinic Proc 44:260-271, 1969.
of
pulmonary
1038, 1983.
6.
Kradin , R. L., and Mark, E. J.:
lung with a theory regarding
Benign lymphoid disorders of the
their development.
Hum Pathol
14:857-867, 1983.
7.
L'Hoate , R. J., Jr. 1 et al: Primary pulmonary lymphomas: a
clinical pathologic analysis of thirty six cases. Cancer 54:1397-
1406. 1984.
Case 10
Diagnosis:
Small intestine; malignant lymphoma, B-cell immunoblastic sarcoma subtype.
This is an example of a primary small intestinal lymphoma of the
Western epidemiologic type because it is spontaneously occurring
without any mucosal background abnormalities. The neoplasm is transmurally invasive.
It is composed of large pleomo rph ic cells with
abundant cytoplasm which contain plentiful rough endoplasmic reticulum
and monoclonal IgM lambda immunoglobulin.
These features allow us t.o
classify it as indica ted above.
In some sections, there are mucosal
nodules of follicular center cell lymphomas of mixed small and large
cleaved cell type, indicating that the main mass is really a transformed lymphoma.
Gastrointestinal lymphomas can be separated into three epidemiologic
categories: the Western or spontaneous or sporadic type, a sprueassociated which occu rs against a background of primary malabsorption,
an d a Mediterranean type which arises, generally in young people high
in the intestines which have a diffuse plasmacytosis in the lamina
propria. A number of patients with this last type have a circulating
alpha heavy chain.
In this country, with only infrequent exceptions,
the lymphomas are of the Western type. Over half occur in the stomach
with decreasing frequency as the more distal parts of the bowel are
reached. Recent studies suggest that a number of factors are related
to prognosis.
Most importa nt appears to be the stage, especially the
involvement of intra-abdominal lymph nodes, but with sophisticated subtyping, certain cell types seem to be prognostically related. The site
of origin also appears to be related to prognosis, but this may be the
same variable as stage. Thus, although gastric lymphomas have the best
prognosis and colo rectal lymphomas have the worst, gastric lymphomas
also have the lowest frequency of regional node involvement, while
colonic lymphomas have the greatest.
References
1.
Rather than list a pile of papers here, the audience is referred
to a symposium on gastrointestinal lymphomas which is scheduled to
appear in the Am J of Surg Path, supposedly in the January, 1985
issue. This i n cludes papers by Appelman on the general pathologic
aspects of gut lymphomas, Daniel Knowles on the r ·e cent classification schemes, Leonard Kahn on histiocytic and hist iocyte rich gut
lymphomas, and Peter Isaacson on B-cell gut lymph.o mas.
2.
Isaacson, P. G., et al:
Multiple lymphomatous polyposis of the
gastrointestinal tract. Histopathology 8:641-656, 1984.
3.
Platz, C. E.: Lymphoid proliferations of the stomach. Chapter 8
in Pa thology of the Esophagus, Stomach, and Duodenum, Appelman, H.
D. (Ed), Churchill Livingstone, New York, 1984.
Case 11
Diagnosis:
Testis
and
paratesticula r
tissues;
adenocarcinoma
presumably metastatic from somewhere else ass ocia t ed
with ectopic hormone production.
This is a classical example of something in the wrong place doing the
wrong thing.
In the region of the epididymis or base of the spermatic
cord, there is an adenocarcinoma with a variety of patterns including
well differentiated and desmoplastic diffuse spreading.
The tumor
cells permeate lymphatics, and nests of tumor can be found within the
testis proper. The testicular tissues are strikingly altered by a very
intense hyperplasia of the interstitial cells and virtually total
tubular atrophy.
The clinical history tells us that this tumot: is
associated with high circulating levels of human chorionic gonadotropin.
Additional information from Dr. George Farrow of the Mayo Clinic
includes the fact that there was an elevated serum CEA and a normal
alpha -fetoprotein.
The patient died, presumably secondary to massive
pulmonary emboli. An autopsy was performed, but a clear primary site
was not found. Metastatic carcinoma involved the liver, the peritoneal
surfaces and the omentum and seemed to be quite promi nent in the
gallbladder bed.
However, a review of the previously resected gallbladder was done and no neoplasm was found in that specimen .
The
differenti al diagnosis includes primary test icular t umors and carcinomas of associated structu.r e s such as the rete and the epididymis.
This neoplasm has no resemblance to any testicular germ cell tumor;
instead, it is clearly a differentiated adenocarcinoma.
One might
wonder if it could have arisen in a teratoma, but then one needs the
tera toma to make that decision.
Carcinomas of the rete and of the
epididymis are unusual and the diagnosis would require some in situ
carcinoma or dysplasia in these structure& for verification. Instead,
the most likely diagnosis is a metastatic u (denocat:cinoma with ectopic
HCG production.
In a recent review of tumors metastasizing to the
testis by Haupt and colleagues from Johns Hopkins, it was found that
the most common sites of tumors metastasizing to testis were, in order,
prostate, lung, c utaneous melanoma, colon, kidney, stomach, and pancreas.
At the same time, the most common tumo rs associated with ectopic
HCG production are carcinomas from the stomach, pancreas, and liver.
This tumor has morphologic features which could be either from a
gastric or a pancreatic pt:imary; the problem is that no primary tumor
in either site was found at the autopsy.
As a re sult, this case
remains enigmatic.
References
1.
Haupt, H. M., et al:
Metastatic c arcinoma involving testis:
clinical and pathologic distinction f r om prima r y testicular
neoplasms. Cance r 54:709-714, 1984.
2.
Kodama, T., et a l: Production of alpha - fetoprotein, normal serum
proteins, and human chorion ic gonadotropin in stomach cancer:
histologic and immunohistochemical analysis of 35 cases .
Cancer
48:1647-1655, 1981.
~.
Uchida, T., et al:
Gonadotropin and alkaline phosphatase producing occult gastric carcinoma with widespread metastasis of generalized bone. Cancer 48:140-150, 1981.
4.
Case records of the Mass a chusetts General Hospital, Case 34, 1983,
discussed by Dr. Marc B. Garnick. N Eng J Med 309:477-487, 1983.
(I am indebted to Dr. George Farrow, who, in turn, is indebted to
one of h is hous e officers, for this reference which discusses a
whole lot of problems relating to this case.)
Case 12
Diagnosis:
Endometrium; papillary adenoma of mixed endometriod,
mucinous and possibly even serous type with foci of
borderline (low malignant potential) epithelium.
This endometrial tumor may or may not have had anything to do with the
radiation that this woman received 30 years earlier for squamous cell
carcinoma of the cervix. What is apparent is the fact that this tumor
does not look like it belongs in the endometrium.
Instead, it is a
dead ringer for the whole variety of papillary cystic ovarian tumors.
In this particular case , there is no cyst, unless one looks upon the
entire endometrial cavity as a cyst. The neoplasm is distinctly papillary, and the papillae have abundant stroma in general, much of which
resembles ovarian stroma.
For the most part,the lining epithelium is
simple columnar, some of which has abundant basilar glycogen.
Other
epithelium is mucinous, much like endocervical epithelium, and, in
addition, there are a variety of other epithelia varying from cuboidal
to flat.
In some foci, there is stratification of the epithelium with
slight variation in nuclear size and staining, rare mitoses, and
apparent exfoliation of clusters of cells. ' rT,hese are the features
which have been described in borderline or low malignant potential
epithelium in ovarian tumors, and I see no reason not to apply the same
c ri teria to this endometrial tumor.
It does not appear that this
lesion invades the myometrium. This tumor seems to be quite distinctive. In fact, I'm not sure I could even find reference to it specifically in any of the major tomes or papers on endometrial neoplasia. It
does not clearly fit i nto the categories of papillary carcinoma of the
endometrium which is supposed to look exactly like the typical papillary carcinomas of the ovary, although this may well be a precursor
lesion. ·At the same time, it does not look much like lesions described
as papillary adenofibromas of the endometrium since they tend to have
the big bulky papillae, much like the ir ovarian counterparts .
References
1.
Hart, W. R.:
Ovarian epithelial tumors of borderline malignancy
(carcinomas of low malignant potential).
Hum Pathol 8:541-549,
1977.
2.
Christopherson, W. M., et al:
Carcinoma of the e ndometrium. II.
Papillary adenocarcinoma: a clinical pathological study of 46
cases. Am J Clin Pathol 77:534•540, 1982.
3.
Hendrickson, M., et al:
Uterine papillary serous carcinoma: a
highly malignant form of endometrial adenocarcinoma.
Am J Surg
Pathol 6:93-108, 1982.
4.
Vellios , F.: Papillary adenofibroma-adenosarcoma; the uterine
cystosarcoma phyllodes.
Chapter 11 in Progress in Surgical
Pathology, Vol. I, Fenoglio, C. M., and Wolff, M. (Eds). Masson
Publishing, New York, 1979.
5.
Zaloudek, C. J. and Norris, H. J.: Adenofibroma and adenosarcoma
of the uterus: a clinicopathologic study of 35 cases .
Cancer
48:354-366, 1981.
6.
If somebody has a reference specifically to cases of this type,
both I and my gynecologic pathology colleague would love to hear
about it.
Case 13
Diagnosis:
Parathyroid gland; carcinoma.
This case is, fortun.a tely, the only endocrine tumor in the entire
seminar, and, since case 1 was a malignant fibrous histiocytoma, this
combination means that the seminar is a success.
Case 13 is a model
for determination of the name that belongs to a large parathyroid. The
choices include hyperplasia, adenoma, and carcinoma.
We assume that
this is a single enlarged parathyroid, and that, coupled with the large
size of this lesion, tends to reduce the differential to adenoma and
carcinoma.
There are a number of criteria which have been devised for
telling one from the ot.h er.
Thus, according to Castleman and Roth,
carcinomas are likely to have cells arranged in a trabecular pattern in
a large gland which is traversed by thick collagen bands. In addition,
there is likely to be nuclear palisading, mitoses, presumably the best
single criterion, possible invasion of the caps..ule or of adjacent
vessels, a striking uniform or boring cell population, and cells which
are larger than those found in other parathyroid conditions.
None of
these criteria, it seems, with possibly the exception of invasion, are
all or none for carcinoma, nor are the lack of such criteria all or
none for adenoma.
Nevertheless, taken in combination, this lesion
clearly is a carcinoma, and we can leave it at that.
References
There really is only one reference regarding parathyroid carcinoma.
The tumor is so rare that nobody has a great deal of experience with
it. The best single discussion appears in the AFIP Fascicle, on tumors
of parathyroid written by Castleman and Roth and published by the
Ame r ican Registry of Pathology in 1977.
Case 14
Diagnosis:
Colon;
adenomatosis coli (formerly
multiple familial polyposis).
referred
to
as
This is the best model for studying the evolution of neoplastic or
dysplastic epithelium in the colon from the smallest focus in the flat
mucosa tttrough progressively larger foci, culmina ting in neoplastic
elevations above the flat mucosa (polyps). The smallest identifiable
neoplastic epithelium appears on the surface and in the superficial
third of an underlying crypt, a zone normally incapable of replication.
Some factor or factors promote a new replicative zone in this region
with the formation of proliferating, less differentiated cells, the
basic neoplastic or dysplastic epithelium. From t h is point, it appears
that buds penetrate downward into the lamina propria and additional
II
luminal crypts are also involved.
The buds may secondarily undergo
further budding to form localized expansions or the epithelium may pile
up lumenward, e x panding the intercryptal lamina propria, resulting in
two dimensional elongated projections or villi.
The results will be
adenomas of varying histologic patterns from tubular to villo·us or any
mixtures.
No matter what the pattern, however, the epithelium is the
same.
What we do not understand is what signals encourage one pattern
of growth as opposed to another.
These mucosal abnormalities can be
studied best utilizing the en face dissection techniques of Hamilton
and his friends in which a square of mucosa is dissected from the
muscularis propria, flat te ned, and embedded face down for sectioning
parallel to the surface.
Using such techniques, the tiny surface foci
and single crypt adenomas are readily \ seen against the background of
normal crypts.
·,
This disease is also accompanied by a risk of colonic carcinoma which
approximates 100%.
Thus, it serves as .an excellent model fo.r studying
the adenoma-carcinoma sequence in the large bowel.
What we know of
this sequence and the interrelation between adenoma and carcinoma in
the colon is swnmarized as follows with a few beginning definitions:
Neoplastic Polyps of the Colon
A.
Definitions:
l.
Benign Neoplastic or Adenomatous Epithelium
A change in cytologic characteristics of mild to moderate
anaplasia, short of that degree of anaplasia which would be
considered carcinomatous, a magical visual perception.
A
synonym for this type of epithelium which is currently
achieving favor is "dysplasia of low or moderate degree".
2.
Adenoma or Benign Epithelial Neoplasm
Any collection of adenomatous epithelium, no matter how
small.
The tiniest recognizable adenoma might be no larger
than the upper part of a single crypt. The larger ones will
be polyps of some pattern or another.
Adenomas may be
predominantly tubular, villous, or mixed.
3.
4.
Villou·s - Having Thin Surface Projections
a.
Gross villi (3-dimensional): finger-like
projections.
b.
Gross villi (2-dimensional): thin projections covered by epithelium. This corresponds either to gross villi of gross folds
or corrugations.
Tubular: The 2-dimensional pattern characterized by
many cross-sections of round, epithelially-lined
structures with central lumens (crypts, tubul.es).
i
5.
Tubulovillous:
A pattern comp osed of both 3 and 4.
The Adenoma-Carcinoma Sequence I n the Colon
l.
By definition, adenomatous and carcinomatous epithelium
are both neoplastic p roliferations. Adenomas of all
patterns (tubula r , villous or mixed) contai n the same
epithlium).
2.
Adenomatous epithelium has a cyto logic s pect rum from t .h at
which closely caricatures normal colonic epithelium, through
an endless series of gradually inc rea sing anaplasia& or
grades of dyspl as ia , somewhere on the far end of which is
carcinomatous
epithelium .
The
surgical pathologist is
constantly faced with the question of where i n that anap lastic array does carcinomatous epithel ium appear.
It is also
obv ious that on occasion, epithelium whi ch might otherwise be
considered adenomatous, is found within an invasive carcinoma.
Therefore, it becomes apparent that there is no clearly
defined point in the anaplasti c spect rum which separates
adenomatous from carcinomatous epithelium.
3.
Adenomas frequently contain foci of severe anaplasia or high
grade dysplasia or carcinoma.
The adenomas most at risk are
the larger ones and thos e with a prominent villous component.
' size seems to be the most i mp ortant risk factor. The carcinomas will first appear as intramucosa l foci and later as
invasive lesions. Invas ion is defined as penetration beneath
the muscularis mucosae.
4.
If typical invasive colonic carcinomas are careful ly sampled,
adenomatous epithelium wil l ofte n be found at the ma rgins.
This is most likely i n smaller carcinomas, but the c hance
increases with the number of marginal sections sampled. even
in larger cancers.
5.
Carcinomatous foci (high g rade dysplasia) confin ed to the
mu cosa of adenoma s are not clinical carcinomas .
They will
not metastas ize because the colonic mucosa does not contain
lymphatics.
This has led some investigators to r ecommend
that the term "carcinoma in situ" or "intramucdsal ca r c inoma"
be d ropped so as to avoid unne cessary anxiety on the part of
endoscopis t s and prevent unnecessary cancer operations for
clin ically benign, although cytolog ica lly malignant lesions.
Colons which contain an ad enoma o r ade nomas with highly
anaplas tic or dysplastic (carcinomatous) epithelium are more
at risk to develop invas ive carcinomas than colons wh ich
contain adenomas with more bland ep i thel ium.
Therefore, i t seems logical that the endoscopist should be
made aware of any seve rely anaplastic or dysplastic epithelium so tha t the patient can be more closely followed than
might o therwise be the case. If a surgical pathologist works
closely with his clinical colleagues and knows that. they
understand the sign ifican ce of these terms, there is no
•I
•
reason why they may not be used.
7.
It bas been shown in one very large series that removal of
all grossly visible adenomatous tissue during sigmoidoscopic
exams
dramatically
cuts
the
incidence of rec tos igmoid
1
carcinoma.
'
8.
These features, coupled with considerable epidemiologic data suggest that adenomatous epithelium is
the precursor of usual or ordinary colonic carcinoma.
A recent multifactorial theory of colonic carcinogenesis, taking a ll of
these factors into considera t ion, may be summarized as follows:
t.he
first factor is a genetic predis position to colonic neoplasia so that
the first step in carcinogenesis is the existence of a genetically
primed colonic epithelium.
This is acted upon by the second factor,
most common in western societies, which causes the epithelium to become
adenomatou s . A third factor then causes this adenoma to grow to form a
large adenoma, since large adenomas are the ones at risk.
Finally, a
fourth factor ca u ses the adenoma to become carcinomatous.
Although
this theory is not totally proved, it is probably the best to date.
Keep tuned to this station for further developments.
References
1.
Bussey, H., J. R.:
Familial polyposis coli.
Path Ann: 14(1):61,
1979.
2.
En face histopathologic technic for
Hamilton, S. R., et al:
exam1 n1ng colonic mucosa of resection specimens. Am J Clin Pathol
78:514- 517, 1982.
3.
Etiology of adenoma-carcinoma
Hill, M. J., et al:
large bowel. Lancet, 1978 (1):245-247.
4.
Sherlock, P., and Winawer, S. J.:
Editorial: are there markers
for the risk of colorectal cancer? New· Engl J Med 311:118-119,
sequence in
1984.
Case 15
Diagnosis:
Colon; ulcerative coli t is with dysplasia.
The following is a brief summary of the colitic-dysplasia-carcinoma
seque nce, bo th for ulcerative colitis and Crohn' s disease.
More detailed information is available, especially in reference 1 below,
copies of which can be obtained from the National Foundation For Ileitis and Colitis, Inc., 295 Madison Avenue, New York , New York 10017.
Carcinoma of the colon is a recognized complication of ulcerative
colitis.
A number of studies have indicated that those coliti cs most
at risk have had disease for 10 years or more and have total colitis,
that is, disease extending from the cecum through t.be rectum.
Some
studies indicate that the risk of carcinoma increases about 2% per year
after the first decade of disease, while in other studies, the risk is
much less.
Initia lly, it was thought that c h ildhood-onset colitis
carried a greater risk tban adult-onset disease, but childhood coli tis
is more likely to be tota l than adult colitis, and the extent of the
disease, rather than the1 age of the patient, is the critical fac t or.
The activity of the d i sease, once considered an important determinant,
is no longer significant.
Those with mild or intermittently active
disease a nd those with almost continuously act ive disease have much the
same risk .
As a r esult of this data, two options are available t o the patients
with colitis.
For those with total colitis and 10 years of disease,
prophylactic colectomy may be considered.
Howeve r , many such patients
are rel a tively young, a nd they have lived with their d isea se and
adjusted to it for years; for many the prospect of a colectomy with the
resultant permanent ileostomy is n ot acceptable.
The newer procedure
of total proctocolectomy and ileoproctostomy may become a sati sfactory
option for these pati ents.
Another option is th at the patients can be followed in an at tempt to
determine more definitively when they are at great risk o f developing
carcinoma.
However, there must be some end-point determinant which
indicates that ca rcinoma is imminent or nearly so, and that colectomy
is necessary.
This end-point is called "high grade dyspl a sia" of the
colonic epithelium.
The colitic carcinoma must arise from some form of an in situ lesion.
If that lesion can b e identified in biopsies, and if the association
with concurrent o r subsequent carcinoma is solid, tbe.n the finding of
such an in situ lesion can serve as the necessary mar ker of h igh risk.
Morson and Pang in 1967 publicized a series of neoplastic or dysplastic
alterations i n the colitics which seemed t o satisfy the necessary
assoc iations. This epithelial change resembled epithelium seen in many
colonic adenomas, especially the larger ones, which were given names
such as "severe atypia" or "carcinoma - i n-situ" . In the coli tics, they
tended to occur i n flat mucosa or plaque-like elevations and were
c ha r acte.r ized by len gthening and d i stortion of the crypts, often a
villiform surface, de creased muc i n , increased n uclear to cytoplasmic
ratios, cellular and nuclea r crowding wi th stratifica tion of the nuclei
so that many nuclei we re near the luminal surface, variable nuclear
pleomorphism, a hig h mitotic rate, and, in the most extreme forms, the
presence of secondary lumens in epithelial clusters.
Furthermore, it
a ppeared that the finding of such changes, especially in multiple leve l
biopsies and/or in sequential biopsies, indicated a high proba bility,
up to 40 or 50%, that t h e colon al ready contained an invasive c arci noma
somewhere.
Additional data, altho ugh sketchy, suggest that lesser
degrees of these epithelial abnormalities may be associated with a
lower, but definite, risk of concu rrent ca r cinoma.
Finally, some
studies using these dysplastic cha nges as an end point have suggested
that the concur rent carcinomas, once found, may be predominantly low
stage les ions if surveillance is frequent and careful.
Presumably,
suc h low stage lesions are likely t o be c urable.
As a result, it is now recommended that sc ree ning of colitics , main l y
by colonoscopy and f astidious multiple lev el biopsy , begi n sometime
;
before the 10 year point, possibly at 7 or 8 years, in order t o detect
the ea rlies t dysplastic changes.
l
A major defect in this detection scheme has been a need for clearly
establ ished d iagnostic criteria for dysplasia.
The coli tic colon is
subject to periodic bouts of activ~ty with epithelial damage and resultant regeneration which may assume quite bizarre cytologic proportions.
To the unwary or inexperienced pathologist, such repairat i ve
epithelia may be diagnosed as dysplasia, and needless colectomy may be
performed. Thus, over the past 4 years, a sroup of 12 p athologists and
an epidemiol ogist have been engaged in a study to define all the
epithelial changes wh ich occur in colitis with con centration on true
dysplasias and separation of them from regeneration.
The res ults of
this study and an atlas comprise the paper in Human Pathology.
The study separated the epithelial changes into t hose which were not
dysplastic and those which clearly were. Most important, however, was
the recognition of epithelial alterations which were on the borderline
or which we re inde finite for dysplasia.
As a result, a series of
recoiMlenda tions for f u rther management were prepared for each of the
categories of e p ithelium based upon c urrent knowledge, but with full
recogni tion that such recommendations must be tested prospectively over
a period of years. These catego ries are summarized as follows:
BIOPSY CLASS
SUGGESTED
MANAGEMENT
Negative For Dysplasia
1.
Normal mucosa
2.
Inactive (quiescent ) d isease
" 3.
Active disease with obvious
regenerat ion .
Continue the program
of regular follow-up.
Indefinite For Dyspla sia
1.
Probably inflammatory-induced
change s
2.
Unknown epithelial c hanges
which may or may not be
dysplasti c .
3.
Probably dysplasti c c hange .
Sho rt interval fo llowup.
Positive For Dysplasia
1.
Low grade.
Short interval followup . Cons ider colectomy
es pecial ly with mass
lesion.
2.
High grade.
Advise colectomy after
confirmation to avoid
false positive interpretation.
r-
CROHN' S DISEASE
Similar dysplastic changes have n ow been detected in colons and small
intestines of patients with long-standing Crohn's disease.
However,
they have not yet been shown to be useful in cancer and pre-cancer
detection in this setting for several reasons.
First, the risk of
carcinoma complicating Crohn' s disease is much less than it is for
ulcerative colitis, although the risk is still greater than in the
general population.
Second, Crohn's disease more commonly affects
small intestine than colon, and endoscopic surveillance thus become s
useless.
Peculiarly, there are two populations of patients reported in the
literature to have carcinoma complicatin g Crohn' s disease.
The first
is a younger group with known long-standing disease a nd carcinoma i n
either small bowel or colon.
The second group, however, are older
patients with total duration of symptoms of a few months, and only
colonic carcinomas.
This latter group is like a group of colonic
carcinoma patients in all respects except for the microscopic findings
of features resembling Crohn' s disease around the invasive carcinoma.
We now know that Crohn's-like reactions with transmural lymphoid
aggregates, neuromuscular hyperplasia, ulcers, and even an occasional
granuloma may be found adjacent to any mass lesion in the bowel,
including carcinoma and lymphoma.
Presumably then, this latter group
of older patients do . not have Crohn's dis e a s e at all, but simply have
colonic cancers with Crohn's-like reactions at their margins.
1.
Riddell, R. H., et al:
Dysplasia in inflammatory bowel disease:
standardized classification with provisional clinical applica tions. Hum P a thol 14:931-968, 1983.
2.
Morson, B. C. a nd Pang, L. S. C.:
Rectal biopsy as an aid to
cancer control in ulcerative colitis. Gut 8:423, 1967.
3.
Simpson, S, et al:
The histologic appearance of dysplasia (pre carcinomatous change) in Crohn' s dise a se of the small and large
intestine. Gastroenterology 81:492, 1981.
4.
Shorter, R . G. :
Risks of intestin al cancer in Crohn' s disea se.
Dis Colon Rectum 26:686-689, 1983.
Case 16
Diagnosis:
Stomach; mucosal polyps with mixed features ot hype rplastic type and adenoma type (inflamed adenomas).
Superimposed high-grade dyspla sia.
1"7
The samples are from several different polyps, all from the same
stomach. · They vary in the relative amount of epithelium and stroma.
In general, the epithelium is of a pit or surface gastric type which
extends from the surface into the stroma wher e it lines complex,
apparently branching tubules.
The epithelium has variable degrees of
dysplasia , (~om mild which closely caricatures normal to more severe,
in which there is diminution in mucus production, stratification of
nuclei, some reaching the luminal face, some nuclear pleomorphism, and
mitoses.
In some areas, distinct intestinal type goblet cells can be
seen scattered among the pit epithelium.
Some of the polyps also
contain areas of high-grade dys.p lasia with such profound loss of
architecture that the designation 11 intramucosal carcinoma 11 is valid.
The lamina propria i .s quite variable.
In some of the polyps, there is
relatively little lamina propria; the bulk of the polyp is epithelial.
However, in others, the lamina propria is inflamed an.d hypervascular
with the surface of the polyp being coarsely papillary.
These later
features are seen in hyperplastic polyps.
Therefore, these polyps
share features o f adenomas and hyperplastic polyps.
It is probably
best to consider them as examples of inflamed or traumatized adenomas.
(
The classification of gastri c mu cosal polyps is complex,
following is a reasonably satisfactory and useful system.
I.
but
the
Neoplast ic
A.
Adenomas.
These are intraepithelial
plasias with grades from low through
dysplasias occur in the stomach:
neoplasias or dyshigh.
Two types of
1.
The intestinal type occurs against a background of
intestinal metaplasia and has metaplastic features
itself, such as the format ion of goblet cells containing
acid mucins .
2.
The pit or foveolar type produces only neutral
mucins.
The background mucosa may have intest-inal
metaplasia.
We may not be able to identify the lowest
grades of pit dysplasia, because there are no firm
criteria.
(In other words, we don't know how.)
At present, we do not know if these two types differ epidemiologically or clinically or by location. Both types may
evolve into carcinomatous epithelium.
Pecu.liarly, although
high-grade dysplastic or carcinomatous epithelium is common
in gastric adenomas, metastasizing carcinomas rarely occur.
B.
II.
Rare carcinomas are polypoid .
These are likely to be superficially invasive (low stage) in spite of large size, accounting for unusually good prognosis.
There are three types of hamartomatous polyps.
A.
Peutz-Jegbers.
Gastric P-J polyps are less common than
the small intestinal ones. They tend to be antral,
lobulated and composed mainly of elongated, tortuous, or
even cystic pits with little participation by the
glands.
Branching muscularis mucosae, so prominent in
the- small intestinal and colonic P-J polyps, is much
1ess impressive in the gastric ones.
III.
B.
Juvenile.
These rounded inflamed polyps with superficial (pit) cysts occur in the stomach in diffuse
gastrointestinal
juvenile polyposis.
They resemble
their colonic counterpart.
However, since they also
look a lot like gastric hyperplastic polyps, it is
almost impossible to diagnose a solitary gastric juvenile polyp.
C.
Fundic Gland Polyps.
These are fairly common, tiny,
often multiple, dome-shaped lesions seen mostly in the
upper body and fundus.
They are composed of nodules of
glands and/or pits.
Initially they were descr:ibed as
being part of the gastric manifestations of ade noma to sis coli, but recent reports indicate that they may
occur i n the absence of that syndrome, especially in
middle aged women.
When associated with the syndrome,
they may disappear after colectomy, but they also may
disappear spontaneously or they may persist.
Who knows? Inflammatory?
These are common, mainly antral
polyps with p r edominant pit hyperplasia. They may or may n ot
be related. The reason for their being is not clear.
A.
Focal Foveolar Hyperplasia.
These tiny sessile antral
bumps are probably the most common of all gastric
polyps . They are characterized by a cluster of elongated, slightly tortuous, sometimes dilated or serrated
pits on top of normal glands.
In some, the lamina
propria may be a bit edematous and inflamed.
These
polyps r~semble the common colonic hyperplastic polyps,
but it is not known if their cellular turnover dynamics
are the same.
B.
Hyperplastic Polyps. These may be the most common large
(over 5 mm) polyps, but this is debatable.
They have
also been called "regenerative" and "hyperplasiogenous".
They share the same name with the common tiny colonic
polyps, but they are entirely different.
Hyperplastic
gastric polyps tend to be inflamed with variably fine
or coarse surface projections and excessive pit hyperplasia with apparent branching and many deep cysts .
These polyps evolve through entirely unknown mechanisms.
Possibly a focal folveolar hyperplasia is the initial
step.
It has been suggested that these polyps are
inflammatory induced, yet they don't occur in stomachs
with ulcers, nor in any specific inflammatory condition we know of.
Actually, some or even all, may be
pit adenomas with low grade dysplastic epithelium that
we are c ur rently unable to identify by light microscopy .
IV.
Tough, or Even Impossible To Classify.
Some gastric polyps
don't clearly fit into any of the above categories . Usually,
these have features of both adenomas or carcinomas and hyperplastic polyps.
Some of these occur in gastroenterostomy
stomas .
References
1.
Gastric polyps: Their
Laxen F, Sipponen P, Ihamaki T, et al:
endoscopical
characteristics
and relation to
morphological and
Acta
Pathol
Microbiol
Immunol
Scand (A)
gastric carcinoma.
90 : 221, 1982.
2.
Ueno K, Oshiba S, Yamagata S, et al: Histoclinical classification
and follow-up study of gastric polyp. Tohuku J Exp Med 118(Suppl):
23, 1976 .
3.
Koch H. K, et al:
Polyps and polypoid foveolar hyperplasia in
gastric biopsy specimens and the ir precancerous prevalence. Front
Gastrointest Res 4:183, 1979.
4.
Laxen F:
Gastric polyps
13:154, 1981.
5.
Elster K: Histologic classification of gastric polyps.
Pathol 63:78, 1976.
6.
Muller-Lissner SA, Wiebecke B:
Investigations on hyperplasiogenous gastric polyps by partial reconstruction. Pathol Res Pract
174:368, 1982.
7.
Ranzi T, et al: Gastric and duodenal polyps in familial polyposis
coli. Gut 22:363, 1981.
8.
Utsunomiya J, et al: Gastric
col~.
Cancer 34:745, 1974.
9.
Watanabe H, Enjoji M, Yao T , et al:
Gastric lesons in familial
adenomatosis coli. Hum Pathol 9:269, 1978.
10.
Tatsuta M, Okuda S, Tamura H, et al: Gastric hamartomatous polyps
in the absence of famlial polyposis coli.
Cancer 45: 818, 1980.
11.
Lida M, et al:
Spontaneous disappearance of fundic gland polyposis:
Report of three cases.
Gastroenterology 79:725, 1980.
12 .
Kamiya T, et al: Long-term follow-up study on gastric adenoma and
Cancer 50:2496,
its relation to gastric protruded carcinoma.
1982.
13.
Appelman, H.D.: Localized and extensive expansions of the gastric
mucosa: mucosal polyps and giant folds. Chapter 3 in Pathology of
the Esophagus,
Stomach and Duodenum, Appelman, H.D., Ed.,
Churchill Livingstone, N.Y., 1984.
and
gastric
lesions
carcinoma.
in familial
Ann Clin Res
Curr Top
adenomatosis
Case 17
Diagnosis:
Anus; cloacogenic carcinoma (proximal epidermoid or
squamous carcinoma).
From the clinical description, it appears that this lesion was centered
proximally in the anus or distal rectum or at the junction which is the
equivalent of the embryonic cloacogeni c zone.
This is obviously a
deeply invasive carcinoma that forms lumpy projections, a very characteristic pattern of invasive growth for carcinomas arising in this
region.
The cells are polygonal and tightly compacted. In occasional
foci, the cells become larger with more abundant cytoplasm and clearly
identifiable intercellular bridges. However, clear- cut keratinization
is rare.
In occasional areas, there are spaces among the cells which
resemble lumens, and, with mucin stains, there is a hint that they are
lined by a glycocalyx.
This is the type of tumor which has been designated as a cloacogenic
transitional carcinoma, but equally frequent is the designation of
squamous or epidermoid carcinoma.
Theoretically, there are four
malignancies which arise in the anus.
The most common is represented
by this case, namely a proximally arising carcinoma with a mixture of
transitional and squamous features which is assumed to develop in the
embryonic cloacogenic zone.
This zone is found in the anal crypts between the papillae, but sometimes this epithelium also covers the
papillae and abuts t .h e distal rectal mucosa. Tumors arising in this
region have a variety of patterns, including the present one, some
which are more heavily squamous, and others which resemble lumpy basal
cell carcinomas of the skin and have been given the designation of
"basaloid".
The second variety of carcinoma arises in the distal squamous lined
anal mucosa known as the "pectin".
These often appear to develop in
foci of Bowen's disease, much like what is seen in the vulva, and they
actually may be comparable to vulvar cancers. Possibly 10-20% o f anal
carcinomas develop in this way.
A th ird variety . of carcinoma arises in association with anal fisures
and fistula and' tends to be a well differentiated, mucus producing
adenocarcinoma.
Initially, these were thought to develop from anal
ducts, those duct - like structures which come off the base of the
cloacogenic zone.
A fourth variety is a melanoma which
presumably in the pectinate region.
arises
from
the
melanocytes,
There have been, surprisingly enough, quite a number of studies pertaining to these malignancies of the anus which have been published
within the last few years.
All these indicate, not surprisingly, that
the survival of patients with these tumors is stage relat ed, and that,
from a clinical standpoint, there is probably little difference between
those which arise in the proximal anus and those which arise more
distally.
Reference
1.
A good general reference on neop lasms of the anus is: Helwig, E.
B.: Neoplasms of the anus. Chapter 1 1 in Pathology of the Colon,
Small Intestine, a nd Anus, Norris, H. T. (Ed). Churchi ll Livingstone, New York, 1983.
2.
Frost, D . B., et al:
Epidermoid can cer of the anorectum.
53:1285 - 1293, 1984 (TheM D Anderson Experience).
3.
Boman , B. M., et al:
Ca rcinoma of the anal canal: a clinical and
pathologic study of 188 cases. Cance r 5 4:114-125, 1984. (The Mayo
Clinic Experience).
4.
Jones , E. A., and Morson, B. C . : Muc inous adenocarcinoma in ano rectal fistula e. Histopathology 8:279-292, 1984.
Cancer
Case 18
Diagnosis:
Anus; atypical squamous proliferation, either wel l
differentiated
superficial ly
i nvasive
carci noma or
bizarre pseudoepitheliomatous hyperplasia.
A classical
"voting" lesion .
This is a hype r p l asti c inflamed squamous p rolife r ation which is gener~ lly flat or,
at best, slightly knobby on the surface and has an
i rregular lower bo~:der.
It is compos ed of a squamous cell population
which is dist i nctly different from the adjacent epithelium in that the
cells a re more glassy appearing a n d tend to have more cytoplasm. There
is a reasonably well defined basal layer in places, but this is lost in
other areas.
Mitotic figures are ge nerally conf i ne d to the basilar
epithelium or the epithelium at the edges of the deep nests . Transmigration of leukocytes is common, as is apoptosis.
Occasional small
cellular whorls or eddies can be seen.
Perhaps the most satisfa ctory way of deal i ng with lesions of this type
is simply to designate them as ca r cinomas. If nothing fu rther happens
to the patient, then that does not detra ct from the diagnosis, and, if
metastases develop , then that solidifies the di agnosis. However, there
are certa in peculiarities about this lesion which make that d i agnosis
difficult.
First, it is extremely we ll d i fferentiated wi th a very
irregular lower border and a flat surface.
Thus, i t doe s no t clearly
fit into the category of verrucous carcinoma, because it is not verrucous and because the lower border is so irregular. Second, it arose in
a patient who had a "fibroepi thelial polyp" removed from the anus two
months earlier.
This raises the question as to whethe r the original
lesion was indeed such a polyp and whether the current les ion i s
arising i n the previous operative site.
Such lesions occurring on the skin would likely be considered examples
of pseudoepitheliomatous hyperplasia.
This lesion appears to arise
either i n the perianal skin or very close to it, so that it may be more
a skin lesion t han a mu cosa l lesion. A s u rvey of a numb er of patholog ists who confront lesions of this type in var i ous sites resulted in a
spl it vote between well differentiated carci noma and p se ud oepithelio-
matous hyperplasia.
I t is entirely unsatisfactory to handle a case at
a seminar and leave the diagnosis in doubt. The question b ecomes more
complex when it includes patient management.
For i n stance, should a
further resection be pe rformed, o r should nothing else be done?
Thi s
question will be left for the a ud ience to ponder.
There are no referen ces which c learly relate to this problem .
Case 19
Diagnosis:
Ileum; inflammatory fibroid polyp.
This patient is quite characteristic of those with i nflammatory fibroid
polyps of the ileum in terms of age and presentation with an intussu sception . This mass is composed of a mixture of spindled cells, inflammatory cells, varia ble amounts of colla gen, and blood vessels.
It
abuts against the muscular is mucosae, and the mucosa a nd muscularis
mucosae are oblitera ted where the t umor is ulcerated.
Th is tumor is
peculiar in that the r e is a fair degree of perivascular orientation to
the stromal and inflammatory cells.
Inflammatory fibroid polyps, or, at least, gut masses designated as
such, have been described in all section s o f the gastrointestinal
tract.
However, the two most common sites are the distal stomach and
the distal ileum.
I n the stomach, they are usually s mal l , sessile
nodules' with strikingly ci r c umscribed lower borders and i nfilt r at io n of
the base of the mucos a.
They are rarely symptoma tic .
The gastric
lesions ten d to have a very prominent perivascular cellular orientation.
In contrast, the lesions of the terminal ileum tend t o be
larger, presen t symptomatically as intussusceptions, i nvade the muscularis propria, but have a sharp superficial margin beneath the mucosa.
The perivascular orientation is un commo n in the ileal tumors.
Peculiarly, th e colo nic tumor s tend to look more l ike the gastric, while
the esophagea l look more like t he ileal . As a result of these discrepancies, it is not clear if the lesions in different sites are really
t he same.
No one knows whttt i nf lammatory fibroid polyps are doing there.
The
name s ugges ts that they ar e the result of inflammatory insults, but the
insults have neve r been defined.
A re cent report of familial IFPs may
shed some l i gh t on their histogenesis. Possibly, t hese are some form
o f stromal ma lfo rmation or hama rtoma.
The present case is unusual in the fact t h at the perivascular orienta tion makes this ileal tumor look mo re like a ga stric. However, i ts
relation to the mucosa is less gastric a nd more in testi nal.
INFLAMMATORY FIBROID POLYPS
STOMACH
ILEUM
Age:
Mid 6th decade
Mid 6th decade
Sex:
M sl. > female
M sl > female
....
Site:
Prepyloric
Terminal
Size:
75% 3 em or less
> 2 em (me d 4+)
Sx:
None. Occ. outlet.
obstr. if over
2.5 em.
Int.est. obstr.
(Intussusception)
Lower border:
Submucosa, sharp
MP or subserosa,
infiltrating
Upper border:
Mucosa, infilt..
Submuc. sharp
Micro:
Perivascular
Loose
? Atrophic gastritis
Associations:
None
? Pern. anemia
References
1.
Anthony, P, P. et al: Multiple and recurrent inflammatory fibroid
polyps in three generations of a Devon family: a new syndrome.
Gut 25:854-862, 1984.
2.
Shimer, G. R. , and Helwig, E. B.: Inflammatory fibroid polyps of
the intestine.
Am J Clin Pathol 81:708-714, 1984. (This is a n
outstanding recent reference which pretty much summarizes all the
previous information and raises the points about the different
types of polyps in different sites.)
3.
As
a
result
of
number
2,
no further references
are necessary.
Case 20
Diagnosis:
Liver; hepatoma with a large clear cell component (clear
cell hepatoma, in part).
This is a large hepatic mass found incidently at the time of cholecystectomy.
The tumor is composed of cells with dark cytoplasm a nd
cells with light cytoplasm in roughly equal proportions.
The light
cells are arranged in cords and nests and solid sheets.
They contain
abundant glycogen and presumably lipid droplets as well.
The dark
cells are arranged in cords and nests, often in a vaguely fibrolamellar
pattern, and these cells look much like liver cells. They form lumens,
presumably di lated canaliculi, and occasional bilirubin precipitates
can be found in these holes.
Thus, this is clearly a liver cell
carcinoma.
Clear cells have not been studied in great depth in hepatomas; nevertheless the current data would suggest that perhaps 10% of hepatomas
have many clear cells, they may occur more in hepatomas in noncirrhotics, there does not appear to be any relation to hepatitis B,
and the cells contain glycogen, lipid or both.
The significance of
clear cells in a hepatoma is not clear. Some studies suggest that they
are meaningless, while others suggest that they are markers of a better
prognosis.
If the latter is true 1 then large populations of clear
cells in a hepatoma would have much the same significance as the
f ibrolamellar pattern.
,..._I
References
1.
Buchanan, T. F., Jr . and Huvos, A. G.:
Clear-cell carcinoma of
the liver: a clinicopathologic study of 13 patients. Am J Clin
Pathol 61:529-538, 1974.
2.
Kishi, K., et al: Hepatocellular carcinoma: a clinical and pathologic analysis of 57 hepatectomy cases. Cancer 51:542- 548 , 1983.
3.
Lai, C. L., et al:
cellular carcinoma.
4.
Sasaki, K, et al:
Hepatic clear cell
hypoglycemia and hypercholesterolemia.
S.
Wu, P. C., et al:
Clear cell carcinoma of liver: an ultrastructural study. Cancer 52:504-507, 1983.
6.
Yeung, R. T. T. 1 et al:
Hypoglycemia associated with lipid
accumulation in primary hepatocellular carcinoma. Cancer 32:1482-
1489. 1973.
1510178401
Histologic prognostic indicators in hepato Cancer 44:1677-1683, 1979.
associated with
Cancer 47 :820-822, 1981
carc~noma
Diagnoses:
1. Breast; malignant fibrous histiocytoma (giant cell sub-type),
unless other sections contain invasive carcinoma.
2.
Myometrium; bizarre leiomyoma
3.
Esophagus; pseudosarcomatous squamous cell c arcinoma (polypoid
carcinoma, spindled carcinoma, carcinosarcoma, or any other name
you prefer).
4.
Renal pelvis; spindled transitional cell ca r cinoma.
5.
Vagina; post-operative spindle cell nodule (pseudosa rcoma).
6.
Femur; dediffere ntiated chondrosarcoma i n a patient with multiple
enchondromatosis.
7.
Soft tissue of leg; myxoid chondrosarcoma.
8.
Ple ura; diffuse malignant mesothelioma (sarcomatoid and
desmoplastic mixture, for the purists).
9.
Lung; malignant lymphoma, some small cell category.
10.
Small intestine; malignant lymphoma, B-cell immunoblastic sarcoma
sub-type.
11.
Paratesticular tissues; adenocarcinoma from somewhere with
ectopic hormone production.
12.
Endometrium; papillary adenoma or adenofibroma, of mixed
endometrioid, mu cinous and possibly even serous type. Possibly
some foci of borderline (low malignant potential) epithelium.
13.
Parathyroid; carcinoma.
14.
Colon; adenomatosis coli (a model for the adenoma - carcinoma
sequence).
15.
Colon;
16.
Stomach; mucosal polyps with mixed features of hyperplastic type
and adenoma type (inflamed adenomas). Superimposed high grade
dysplasia.
17.
Anus; cloacogenic carcinoma (proximal epidermoid or squamous
carcinoma).
18.
Anus; atypical squamous proliferation, either well-differentiated
superficially invasive carcinoma or bizarre pseudoepitheliomatous
hyperplasia. A classical "voting" lesion.
19.
Ileum; inflammatory fibroid polyp.
20.
Live r ; hepatoma with a large clear cell component (clear cell
hepatoma in part).
ul~erative
colitis with dysplasia.