FIRST AID HEADQUARTERS, DEPARTMENTS OF THE ARMY, THE NAVY, AND THE AIR FORCE DECEMBER 2002

FIRST AID 

HEADQUARTERS, DEPARTMENTS OF 

THE ARMY, THE NAVY, AND THE AIR FORCE

DECEMBER 2002 

DISTRIBUTION RESTRICTION:Approved for public release; 

distribution is unlimited. 

    Click Link For Download

INGLE'S ENDODONTICS - 6th Ed. (2008)

INGLE'S ENDODONTICS - 6th Ed. (2008)

Front Matter

Title Page

Ingle's

ENDODONTICS 6

John I. Ingle DDS, MSD

Lecturer

Loma Linda University

School of Dentistry

Loma Linda, California

Leif K. Bakland DDS

Professor and Chair

Department of Endodontics

School of Dentistry

Loma Linda University

Loma Linda, California

J. Craig Baumgartner MS, DDS, PHD

Professor and Chairman

Department of Endodontology

Oregon Health & Sciences University

Portland, Oregon

2008

BC Decker Inc

Hamilton

Click Link For Download

Genitourinary Imaging 2nd edition

Genitourinary Imaging 2nd edition

Click Link For Download

Human Osteology and Skeletal Radiology Authors Evan Matshes M.D.

Human Osteology

and Skeletal Radiology

Authors

Evan Matshes M.D.

Associate Member
Department of Anatomy and Cell Biology
College of Medicine
University of Saskatchewan
Brent Burbridge M.D., F.R.C.P. (C)
Professor and Head
Department of Medical Imaging
University of Saskatchewan College of Medicine
Belinda Sher D.M.D.
Dentist
Calgary, Alberta
Adel Mohamed M.D.
Associate Professor
Department of Anatomy and Cell Biology
College of Medicine
University of Saskatchewan
Bernhard H. Juurlink Ph.D.
Professor and Head
Department of Anatomy and Cell Biology
College of Medicine
University of Saskatchewan
An Atlas and Guide

Click Link For Download

Davidson’sPrinciples and Practice of Medicine 22nd Edition

Davidson’sPrinciples and Practice of
Medicine
22nd Edition
Edited by
Brian R. WalkerBSc MD FRCPE FRSE

Professor of Endocrinology,
University of Edinburgh;
Honorary Consultant Physician,
Royal Infirmary of Edinburgh, UK
Nicki R. ColledgeBSc FRCPE
Consultant Physician in Medicine for the Elderly,
Liberton Hospital, Edinburgh,
and Royal Infirmary of Edinburgh;
Honorary Senior Lecturer,
University of Edinburgh, UK
Stuart H. RalstonMD FRCP FMedSci FRSE
Arthritis Research UK Professor of Rheumatology,
University of Edinburgh;
Honorary Consultant Rheumatologist,
Western General Hospital,
Edinburgh, UK
Ian D. PenmanBSc MD FRCPE
Consultant Gastroenterologist,
Royal Infirmary of Edinburgh;
Honorary Senior Lecturer,
University of Edinburgh, UK
Illustrations by
Robert Britton

Click Link For Download

C A S E R E V I E W Obstetric and Gynecologic Ultrasound THIRD EDITION

C A S E  R E V I E W

Obstetric and

Gynecologic

Ultrasound

THIRD EDITION

CA S E R E V IE W S E R IE S

DOWNLOAD

ECGs for Nurses Second Edition Philip Jevon

ECGs for Nurses

Second Edition

Philip Jevon

RGN, BSc (Hon), PGCE, ENB 124

Resuscitation Officer/Clinical Skills Lead

Honorary Clinical Lecturer

Manor Hospital

Walsall

UK

DOWNLOAD

Cellulite Pathophysiology andTreatment

Cellulite

Pathophysiology 

andTreatment

edited by

Mitchel P. Goldman

University of California

San Diego, California, U.S.A.

and

La Jolla Spa MD

La Jolla, California, U.S.A.

Pier Antonio Bacci

University of Siena

Siena, Italy

and

Cosmetic Pathologies Center

Arezzo, Italy

Gustavo Leibaschoff

University of Buenos Aires School of Medicine

and

International Union of Lipoplasty

Buenos Aires, Argentina

Doris Hexsel

School of Medicine

University of Passo Fundo

Passo Fundo, Rio Grande do Sul, Brazil

Fabrizio Angelini

Endocrinology Service Research Clinic Institute Ecomedica Empoli

Florence, Italy

and

University of Parma

Parma, Italy

Cellulite

Pathophysiology 

andTreatment

Published in 2006 by

  Click Link For Download

Acne Symposium at the World Congress of Dermatology

Acne

Symposium at the World Congress of Dermatology

Paris, July, 2002

24 figures, 16 in color, and 18 tables, 2003

Editors

Ch.C. Zouboulis,Berlin

M.I. Herane,Santiago de Chile

D.Thiboutot,Hershey, Pa.

Click Here For Download

Pocket Atlas of Echocardiography Thomas Boehmeke, M.D. Cardiology Practice Gladbeck, Germany

Pocket Atlas of Echocardiography

Thomas Boehmeke, M.D.

Cardiology Practice

Gladbeck, Germany

                                         
   




















  Click Link For Download

Exercise Leadership in Cardiac Rehabilitation An evidence-based approach

Exercise Leadership in                                         

Cardiac Rehabilitation 

An evidence-based approach

Edited by Morag K. Thow Dip PE, BSc, PhD, MCSP

Lecturer in Physiotherapy, Glasgow Caledonian University

Glasgow, UK

Click Link For Download

Textbook of Oral and Maxillofacial Surgery

Textbook of Oral 

and Maxillofacial Surgery

 Click Link For Download

DENTAL ANATOMY AND OCCLUSION

DENTAL
ANATOMY


AND


OCCLUSION

Click Link For Download

Caesarean section. Part 1

Post by Health updates.

Caesarean section. Part 2

Post by Health updates.

CARRANZA’S CLINICAL PERIODONTOLOGY

CARRANZA’S CLINICAL PERIODONTOLOGY 
 ISBN: 978-1-4377-0416-7

Click Link For Download

                                                                    

Fundamentalsof Fixed Prosthodontics ThirdEdition

Fundamentalsof

Fixed

Prosthodontics

ThirdEdition

HerbertT.Shillingburg,Jr ,DD S

SumiyaHobo,DDS,MSD,Ph D

LowellD.Whitsett,DD S

RichardJacobi,DD S

SusanE.Brackett,DDS,MS

quinlc/zenee

Click Link For Download

Case 1: Mitral stenosis

Case 1: Mitral stenosis

INSTRUCTION

This patient developed dyspnoea and orthopnoea during pregnancy, please examine her.
This 55-year old patient has atrial fibrillation, please perform the relevant clinical examination.
SALIENT FEATURES

History

· Symptoms of left-sided heart failure: exertional dyspnoea, orthopnoea, paroxysmal dyspnoea.
· Less frequent symptoms: haemoptysis, hoarseness of voice, symptoms of right-sided failure (these
symptoms are somewhat more specific for mitral stenosis).
· Obtain a history of rheumatic fever in childhood.


Examination

· Pulse regular or irregularly irregular (due to atrial fibrillation). · Jugular venous pressure (JVP) may be
raised. · Malar flush.
· Tapping apex beat in the 5th intercostal space just medial to midclavicular line. · Left parasternal heave
(indicating right ventricular enlargement). · Loud first heart sound.
· Opening snap (often difficult to hear; a high-pitched sound that can vary from 0.04 to 0.10 s after the
second sound, and is best heard at the apex with the patient in the lateral decubitus position).
· Rumbling, low-pitched, mid-diastolic murmur - best heard in the left lateral position on expiration. In
sinus rhythm there may be presystolic accentuation of the murmur. If you are not sure about the
murmur, tell the examiner that you want the patient to perform sit-ups or hop on one foot to increase
the heart rate. This will increase the flow across the mitral valve and the murmur is better heard.
· Pulmonary component of second sound (P2) is loud.
Remember. The signs of pulmonary hypertension include loud P2, right ventricular lift, elevated neck
veins, ascites and oedema. This is an ominous sign of the disease progression because pulmonary
hypertension increases the risk associated with surgery (Bt Heart J 1975; 37: 74-8).

Note
· In patients with valvular lesions the candidate would be expected to comment on rhythm, the
presence of heart failure and signs of pulmonary hypertension.
· In atrial septal defect, large flow murmurs across the tricuspid valve can cause mid-diastolic
murmurs. The presence of wide, fixed splitting of second sound,
absence of loud first heart sound, and an opening snap and incomplete right bundle branch block should
indicate the correct diagnosis. However, about 4% of patients with atrial septal defect have mitral
stenosis, a combination called Lutembacher's syndrome.

DIAGNOSIS
This patient has mitral stenosis (lesion) which is almost always due to rheumatic heart disease
(aetiology), and has atrial fibrillation, pulmonary hypertension and congestive cardiac failure (functional
status).

QUESTIONS

What is the commonest cause of mitral stenosis?
Rheumatic heart disease.

What is the mechanism of tapping apex beat?
It is due to an accentuated first heart sound.

What does the opening snap indicate?
The opening snap is caused by the opening of the stenosed mitral valve and indicates that the leaflets are
pliable. The opening snap is usually accompanied by a loud first heart sound. It is absent when the valve
is diffusely calcified. When only the tips of the leaflets are calcified, the opening snap persists.

What is the mechanism of a loud first heart sound?
The loud first heart sound occurs when the valve leaflets are mobile. The valve is open during diastole
and is suddenly slammed shut by ventficular contraction in systole.

What is the mechanism of presystolic accentuation of the murmur?

In sinus rhythm it is due to the atrial systole which increases flow across the stenotic valve from the left
atrium to the left ventricle; this causes accentuation of the loudness of the murmur. This may also be
seen in atrial fibrillation and is explained by the turbulent flow caused by the mitral valve starting to close
with the onset of ventricular systole. This occurs before the first heart sound and gives the impression of
falling in late diastole; it is, however, due to the start of ventricular systole.

What are the complications?

· Left atrial enlargement and atrial fibrillation.
· Systemic embolization, usually of the cerebral hemispheres.
· Pulmonary hypertension.
· Tricuspid regurgitation.
· Right heart failure.

How does one determine clinically the severity of the stenosis?

· The narrower the distance between the second sound and the opening snap, the greater the severity.
The converse is not true. (Note. This time interval between the second sound and opening snap is
said to be inversely related to the left atrial pressure.)
in tight mitral stenosis the murmur may be less prominent or inaudible and the findings may be
primarily those of pulmonary hypertension.

ADVANCED-LEVEL QUESTIONS

What are the investigations you would perform?

ECG
Broad bifid P wave (P mitrale); atrial fbrillation in advanced disease.
Chest radiography
· Congested upper lobe veins.
· Double silhouette due to enlarged left atrium.
· Straightening of the left border of the heart due to prominent pulmonary conus and filling of the
pulmonary bay by the enlarged left atrium.
· Kerley B lines (horizontal lines in the regions of the costophrenic angles).
· Uncommonly the left bronchus may be horizontal due to an enlarged left atrium.
· Mottling due to secondary pulmonary haemosiderosis.

Echocardiography

2D and Doppler echocardiography is the diagnostic tool of choice for assessing the severity of mitral
stenosis and for judging the applicability of balloon mitral valvotomy (N Engl J Med 1997; 337: 3241).
· It is able to identify restricted diastolic opening of the mitral valve leaflets due to 'doming' of the anterior
leaflet and immobility of the posterior leaflet.
· It also allows assessment of the mitral valve apparatus and left atrial enlargement. · Echocardiography
usually permits an accurate planimetric calculation of the valve area (Am J Cardiol 1979; 43: 560-8).
· It can also be used to assess the severity of stenosis by measuring the decay of the transvalvular
gradient or the 'pressure half-time', an empirical measurement (BrHeartJ 1978; 40: 13140).
· The mean transmitral gradient can be accurately and reproducibly measured from continuous wave

Doppler signal across the mitral valve with the modified Bernoulli equation.
· The mitral valve area can be non-invasively derived from Doppler echocardio-graphy with either the
diastolic half-time method or the continuity equation. The continuity equation should be used when
the area derived from the half-time does not correlate with the mean transmittal gradient.
· Doppler also allows estimation of pulmonary artery systolic pressure from the TR velocity signal and
assessment of the severity of concomitant MR or AR.
· Trans-oesophageal echocardiography is not required unless a question about diagnosis remains
after transthoracic echocardiography.

Cardiac catheterization

· Shows raised right heart pressures and an end-diastolic gradient from pulmonary artery wedge
pressure (or left atrium if trans-septal puncture has been done) to the left ventricle.
· Left and right heart cardiac catheterization is indicated when percutaneous mitral balloon valvotomy
is being considered.
· Cardiac catheterization is also indicated when there is a discrepancy between Doppler-derived
haemodynamics and the clinical status of a symptomatic patient.
· Coronary angiography may be required in selected patients who need intervention.
· Exercise haemodynamics should be performed when the symptoms are out of proportion to the
calculated mitral valve gradient area.
What is the normal cross-sectional area of the mitral valve?
It ranges from 4 to 6 em2; turbulent flow occurs when this area is less than 2 cm2.

What is the area in 'tight' mitral stenosis?

It is usually less than 1 cm2 and consequently the gradient across the valve is >10 mmHg.

How would you manage the patient?

· Asymptomatic patient in sinus rhythm: prophylaxis against infective endocarditis only.
· Mild symptoms: diuretics to reduce left atrial pressure and therefore symptoms.
· Atrial fibrillation: (1) rate control (digitalis, beta-blocker or calcium channel blocker); (2)
anticoagulants (Eur Heart J 1988; 9: 291-4).
· Moderate to severe symptoms or pulmonary hypertension is beginning to develop: mechanical relief
of valve stenosis including (1) balloon valvotomy (N Engl J Med 1994; 331: 961-7; Br Heart J 1988;
60: 299-308) - percutaneous mitral balloon valvuloplasty is usually the procedure of choice when
there is a non-calcified pliable valve; (2) surgery.

What are the indications for surgery?

· Patients with severe symptoms of pulmonary congestion and significant mitral stenosis.
· Patients with pulmonary hypertension or haemoptysis, even if minimally symptomatic.
· Recurrent thromboembolic events despite therapeutic anticoagulation.

Which surgical procedures are used to treat mitral stenosis?

Closed commissurotomy
· Closed mitral valvotomy - involves the use of mechanical dilators, inserted through the apex of the
left ventricle. It is complicated by mitral regurgitation, systemic embolization and restenosis.
· Balloon valvuloplasty (a form of closed commissurotomy) - percutaneous trans-septal balloon mitral
valvotomy (or valvuloplasty). Remember, percutaneous balloon dilatation of the mitral valve is a
useful option in patients who are unable to undergo cardiac surgery, as in late pregnancy or when too
ill (severe respiratory disease, non-mitral cardiac disease, multiorgan failure).

Open commissurotomy
Requires cardiopulmonary bypass and allows surgical repair of the valve under direct vision, resulting in
more effective and safer valvotomy than the closed procedure.
Valve replacement
Entails risks including thromboembolism, endocarditis and primary valve failure.

What factors determine the success of balloon valvuloplasty?

· Good mobility ofthe valves.
· Little calcification
· Minimal subvalvular disease.
· Mild mitral regurgitation.

In which trimester do patients with mitral stenosis usually become symptomatic?

Patients usually become symptomatic in the second trimester of pregnancy, when blood volume
increases significantly and increases pulmonary pressures. As the blood volume diminishes late in the
third trimester, the symptoms might slightly improve.
Mention some rarer causes of mitral stenosis.
· Calcification of mitral annulus and leatlets.
· Rheumatoid arthritis.
· Systemic lupus erythematosus.
· Malignant carcinoid.
· Congenital stenosis.

Which conditions simulate mitral stenosis?

· Left atrial myxoma.
· Ball valve thrombus in the left atrium.
· Cor triatriatum (a rare congenital heart condition where a thin membrane across the left atrium
obstructs pulmonary venous flow).

Have you heard of Ortner's syndrome?

It refers to the hoarseness of voice caused by left vocal cord paralysis associated with enlarged left
atrium in mitral stenosis.

References:
N. Ortner(1865-1935), Professor of Medicine, Vienna, described the syndrome in 1897. He believed in
laboratory research and its application to bedside clinical work and said that the clinician's motto ought to
be '0bers laboratorium dauernd zur Klinik' (translated: 'always via the laboratory to the clinic').
P.J. Kerley (1900-1978), British radiologist.
Paul Wood was a cardiologist at the Hammersmith and National Heart Hospitals. His clinical skills are
legendary and he had a profound influence on British cardiology.
Elliott Cutler, in 1923 in Boston, was the first to attempt surgical treatment of mitral stenosis by inserting a
knife through the apex of the left ventricle and blindly cutting the valve at right angles to its natural orifice.
Henry Souttar, in 1925, relieved mitral stenosis with a finger inserted through the atrial appendage.
In 1948, four surgeons working independently performed successful valvotomies: Horace Smithy, Charles
Bailey, Dwight Harken and Russell Brock.
In 1984, Kanji Inoue from Japan and in 1985, James E Lock, contemporary Professor of Pediatric
Cardiology, Harvard Medical School, and colleagues introduced balloon valvuloplasty for mitral stenosis.

Pathology CASE 10

CASE 10

INTRODUCTION

A 21-year-old nulliparous woman complains of lower abdominal "heaviness." She takes an oral contraceptive and is in a monogamous relationship. On examination, she has a normal-sized, nontender uterus, and a 9-cm right adnexal mass is palpated. Her pregnancy test is negative. On sonography, the mass appears cystic and solid.

· What is the most likely diagnosis?

· What are some of the histologic findings expected in this mass?

ANSWERS TO CASE 10: Ovarian Teratoma

Summary: A 21-year-old nulliparous woman has a 9-cm right adnexal mass that on sonography appears cystic and solid.

· Most likely diagnosis: Benign cystic teratoma of the ovary.

· Expected histologic findings in this mass: Any tissue may be found, but the most common are sebum, skin, hair, teeth, thyroid, and neurologic tissues.

CLINICAL CORRELATION

Introduction

This young woman has an ovarian mass that on ultrasound has cystic and solid components, a classic presentation of a benign cystic teratoma (dermoid cyst) of the ovary. Although benign cystic teratomas are often asymptomatic, larger dermoids (as in this case) can present with pelvic pain, pressure, fullness, or dyspareunia. The patient's pregnancy test was reported as negative; however, in rare cases, degenerating ectopic pregnancies can be missed with urine human chorionic gonadotropin (hCG) assays because of the low sensitivity of urine pregnancy tests in the presence of very low (<25 mIU/mL) serum hCG levels. The fact that the patient is engaged in a monogamous relationship should decrease the risks of her contracting gonorrhea or Chlamydia, hence decreasing the possibility of pelvic inflammatory disease and tuboovarian abscess (TOA). The patient also gives a history of oral contraceptive (OC) use, which also serves to decrease the risk of pelvic inflammatory disease and/or TOA. Oral contraceptives also greatly decrease the likelihood of the mass being a physiologic ovarian mass (follicular cyst, hemorrhagic corpus luteum cyst, etc.). The ultrasound shows a complex (both cystic and solid) ovarian mass, which also is not consistent with an abscess or a physiologic ovarian or paraovarian cyst.

Although some disagreement exists over the timing and indications for surgery in complex masses under 6 cm or simple cysts of any size, a 9-cm complex ovarian mass almost always needs to be explored surgically. This is due primarily to the small but not insignificant risk of malignancy. Upon confirmation of benign intraoperative findings, efforts should be directed at salvaging all normal tissue from the affected ovary and removing only that tissue which has undergone neoplastic degeneration.

Approach to Ovarian Neoplasm

Definitions

Tuboovarian abscess: An abscess formed within the adnexal space consisting of ovary, fallopian tube, and matted bowel caused by untreated or inadequately treated pelvic inflammatory disease.

Endometrioma: A large (6- to 8-cm) loculated collection of endometrial tissue that can develop in the pelvis in females with endometriosis. As this tissue degenerates, it turns brownish in color and is known as a chocolate cyst.

Struma ovarii: A benign teratoma in which functional thyroid tissue is the predominant histologic finding. Approximately 2 to 3 percent of teratomas are classified as struma ovarii. Thyrotoxicosis is clinically apparent in 5 percent of these cases.

Ovarian torsion: A condition in which the ovary twists on its attachment to the infundibulopelvic ligament, thus interrupting ovarian blood supply. This usually is seen in conjunction with pathologic enlargement of the ovary and can be dynamic (intermittent) in nature or complete; the latter results in infarction and necrosis of the affected ovary.

Table 10-1. DIFFERENTIAL DIAGNOSES OF A PELVIC MASS

Full bladder

Intrauterine or extrauterine pregnancy

Functional ovarian cysts (follicular or corpus luteum)

Tuboovarian abscess

Diverticular abscess

Appendiceal abscess

Matted bowel and/or omentum

Paratubal or paraovarian cyst

Stool in sigmoid colon

Leiomyomas (submucosal, subserosal, pedunculated, or intraligamentous)

Pelvic kidney

Mullerian abnormality (e.g., bicornuate uterus)

Benign or malignant ovarian tumors

Discussion

Although they may present in any decade of life, benign cystic teratomas are the most common ovarian neoplasm found in females under age 35 (excluding physiologic follicular and corpus luteum cysts) and are also the most common ovarian neoplasm found in pregnancy. Approximately 10 to 15 percent of all cases involve both ovaries. Table 10-1 lists the differential diagnoses of a pelvic mass, and Table 10-2 lists the categories of ovarian neoplasms.

Table 10-2. OVARIAN NEOPLASMS
Benign epithelial ovarian tumors
	Serous cystadenoma
	Mucinous cystadenoma
	Brenner tumor
Malignant epithelial ovarian tumors
	Serous cystadenocartcinoma
	Mucinous cystadenocarcinoma
	Endometroid adenocarcinoma
	Transitional cell carcinoma
Malignant germ cell tumors
	Dysgerminoma
	Endodermal sinus tumor
	Embryonal carcinoma
	Polyembryonal carcinoma
	Choriocarcinoma
	Teratoma (immature)
Benign germ cell tumors
	Benign cystic teratoma (dermoid)
Sex cord-stromal tumors
	Thecoma
	Sertoli-Leydig cell tumor
	Granulosa-theca cell tumor

Benign cystic teratomas arise from a single germ cell in the ovary and have a normal female karyotype (46,XX). Because of the pleuripotent nature of germ cells, teratomas can differentiate into tissues derived from all three embryologic cell lines (endoderm, ectoderm, and mesoderm). Thus, a "mature" teratoma often contains skin, fat, sebaceous glands, sweat glands, hair, smooth and striated muscle, cartilage, bone, teeth, neural tissue, and gastrointestinal tissue (see Figure 10-1). Functional thyroid tissue is found in approximately 12 percent of benign cystic teratomas, and rarely this tissue will proliferate into the predominant cellular element in the teratoma. This unique teratoma hence is referred to as struma ovarii and will secrete enough functional thyroid hormone to cause acute thyrotoxicosis in approximately 5 percent of cases.

Benign cystic teratomas are usually asymptomatic and are found most commonly during routine gynecologic screening or incidentally during unassociated surgical or radiographic procedures. Larger teratomas give rise to acute adnexal torsion in approximately 11 percent of cases. The increased risk of torsion with teratomas compared with other causes of ovarian enlargement is thought to be due to fat content, allowing the teratoma to "float" in the abdominal cavity instead of lodging against other structures. Other significant complications include secondary infection and acute hemorrhage with the potential for septic and/or hypovolemic shock. Rupture or perforation is seen in less than 5 percent of cases and occurs more frequently in association with pregnancy. When acute rupture occurs, spillage of the contents of the teratoma into the abdominal cavity often precipitates a surgical emergency, whereas more chronic leakage of contents can produce a severe chemical peritonitis that also requires surgical intervention. Malignant degeneration occurs in less than 2 percent of all recognized teratomas.

Other germ cell tumors include dysgerminomas, endodermal sinus tumors, and choriocarcinomas. These neoplasms usually occur in females under age 30 years. Dysgerminomas are rapidly growing and very radiosensitive and chemosensitive. Endodermal sinus tumors often secrete alpha-fetoprotein, whereas choriocarcinomas secrete human chorionic gonadotropin.

Epithelial tumors of the ovary most commonly affect females over age 30 years, particularly postmenopausal women. Malignant serous cystadenocarcinomas are the most common, usually presenting with ascites. Treatment includes surgical excision followed by combination chemotherapy. Mucinous tumors may become very large, sometimes exceeding 30 pounds in weight; their rupture can lead to chronic bouts of bowel obstruction (pseudomyxoma peritonei).

Stromal tumors of the ovary are often functional, secreting estrogen (granulosa-theca cell tumors) or androgens (Sertoli-Leydig cell tumors). These neoplasms can present as precocious puberty, postmenopausal bleeding, or hirsutism. They are usually solid tumors that are slow growing and rarely metastasize early. Surgery is the best treatment for these tumors.

Figure 10-1. Gross photograph of an ovarian teratoma. Note the hair. (Courtesy of Dr. Aaron Han, Reading, PA.)0

COMPREHENSION QUESTIONS

[10.1] A 58-year-old woman is noted to have bilateral adnexal masses on physical examination. Which of the following is most suggestive of these adnexal masses being malignant?

A. CT imaging revealing that they are primarily cystic

B. Elevation of the serum alkyline phosphatase level

C. Family history of lung cancer

D. The presence of ascites

E. The presence of low-grade fever

[10.2] A 25-year-old woman is noted to have a solid and cystic right ovarian mass measuring 10 cm on ultrasound. Which of the following is the most likely histologic subtype?

A. Serous

B. Mucinous

C. Brenner

D. Teratoma

E. Fibroma

[10.3] A 4-year-old girl is noted to have breast enlargement and vaginal bleeding. On physical examination, she is noted to have a 9-cm pelvic mass. Which of the following is the most likely etiology?

A. Cystic teratoma

B. Dysgerminoma

C. Endodermal sinus tumor

D. Granulosa cell tumor

E. Mucinous tumor

[10.4] A 44-year-old woman undergoes an exploratory lapartomy for suspected ovarian cancer. Upon removal of the right ovary, a frozen section reveals "signet ring" cells. Which of the following is the most likely etiology?

A. Dysgerminoma

B. Metastatic

C. Mucinous

D. Serous

E. Teratoma

ANSWERS

[10.1] D. The presence of ascites and ovarian masses is strongly associated with ovarian cancer. Other features of malignancy include solid ovarian masses, bilaterality, and lymphadenopathy.

[10.2] D. The benign cystic teratoma or dermoid cyst is the most common type of ovarian tumor in females younger than age 30 years. Dermoid cysts usually have solid and cystic components.

[10.3] D. This young girl has signs of precocious puberty. Thus, the adnexal mass is likely to be an estrogen-secreting granulosa-theca cell tumor. These low-grade malignancies are slow-growing so-called stromal cell tumors. The androgen-secreting tumors are usually Sertoli-Leydig cell tumors and may cause virilism.

[10.4] B. Signet ring cells suggest a Krukenberg tumor, usually metastatic from the gastrointestinal tract (stomach, colon) or breast. The mucin that fills the cell pushes the nucleus to the periphery of the cell, leading to the appearance of a signet ring.

PATHOLOGY PEARLS

· Benign cystic teratomas are the most common nonphysiologic ovarian tumor in females under age 35.

· Ten to 15 percent of all teratomas are bilateral.

· Ovarian torsion occurs frequently with teratomas.

· The most common ovarian cancers are epithelial in origin and usually occur in postmenopausal women. Surgical excision followed by combination chemotherapy is the best treatment.

· Ovarian cancer is associated with ascites.

· Granulosa-theca cell tumors often secrete estrogen, and Sertoli-Leydig cell tumors often secrete androgens.

· Metastatic tumors to the ovary may have a "signet ring" appearance on microscopy and are called Krukenberg tumors.

REFERENCES

Crum CP. The female genital tract: The gastrointestinal tract. In: Kumar V, Assas AK, Fausto N, eds. Robbins and Cotran pathologic basis of disease, 7th ed. Philadelphia: Elsevier Saunders, 2004:1092-1104.

Novak E, Hillard PA, Berek J. Novak's gynecology, 13th ed. Philadelphia: Lippincott Williams & Wilkins, 2002.

Stenchever MA, Droegmueller W, Herbst HR, Mishell D. Comprehensive gynecology, 4th ed. Philadelphia: Mosby, 2002.

0.515625

Copyright © 2006 by the McGraw-Hill Companies, Inc. All rights reserved.

Pathology CASE 9

CASE 9

INTRODUCTION

A 54-year-old woman notes a 6-month history of progressive vaginal discharge with an odor. She also has noted vaginal spotting after intercourse. She had gone through menopause 2 years earlier and took an oral contraceptive for 10 years. She has smoked one pack of cigarettes per day for 20 years. She denies a cough or dyspnea. She complains of right back pain and right leg swelling. The speculum examination shows a 4-cm irregular fungating mass arising from the cervix.

· What is the most likely diagnosis?

· What is the next step?

· What is the likely pathophysiology for this condition?

ANSWERS TO CASE 9: Cervical Cancer

Summary: A 54-year-old postmenopausal woman has a 6-month history of an odiferous vaginal discharge and postcoital spotting. She has smoked one pack of cigarettes per day for 20 years. She complains also of right back pain and right leg swelling. The speculum examination shows a 4-cm irregular fungating mass arising from the cervix.

· Most likely diagnosis: Cervical cancer.

· Next step: Biopsy of the lesion to confirm the diagnosis, followed by staging to assess the extent of the disease.

· Likely pathophysiology: Human papillomavirus.

CLINICAL CORRELATION

Introduction

This patient most likely has cervical cancer. Indications leading the clinician to the diagnosis in this case include the patient's risk factors and presenting symptoms. Her risk factors for cervical cancer include age, a history of oral contraceptive use, and a history of smoking. The presenting symptoms of malodorous vaginal discharge and postcoital bleeding are characteristic of cervical cancer. The history should guide the clinician to examine the cervix. In this case, a grossly visible lesion was seen on the cervix during speculum examination. The next step in management is to biopsy the lesion for a definitive diagnosis.

Approach to Cervical Dysplasia and Cancer

Definitions

Cervical intraepithelial neoplasia (CIN): Dysplastic growth and development of the epithelial cells of the cervix. Lesions may be defined by mild, moderate, or severe, or CIN I, CIN II, or CIN III (see Figure 9-1).

Human papillomavirus (HPV): A double-stranded DNA virus associated with condyloma, cervical intraepithelial lesions, and cervical cancer. Cellular changes seen in HPV infection include an expanded parabasal cell layer and koilocytes but normal maturation and mitoses. There are over 70 types of HPV, which have varying oncogenic capacities. High-risk HPV types are those most often associated with high-grade lesions and invasive cancer. These types include 16,18, 31, 39, 45, 56, 58, and 68.

Koilocyte: A viral expression of E4 protein that disrupts cytoplasmic keratin matrix in squamous cells and causes pleomorphism, hyperchromasia, perinuclear halos, and nuclear changes, including enlarged nuclei with abnormal edges, multinucleation, and variations in nuclear size.

Figure 9-1. Cervical epithelium showing normal, CIN I, CIN II, and CIN III.0

Discussion

Cervical cancer is the third most common cancer of the female lower reproductive system. More than 80 percent of cervical dysplasias and more than 90 percent of cervical cancers are associated with HPV infection. Because HPV is transmitted through sexual contact, many of the risk factors for cervical cancer involve behaviors that increase the risk of all sexually transmitted diseases. These risk factors include early intercourse, many sexual partners, high-risk sexual partners, infection with other sexually transmitted diseases, and immunosuppression by HIV infection. Relative risk factors may include oral contraceptive use, tobacco use, and immunodeficiency. Other possible risk factors are under investigation.

Cervical dysplasia is found most often in females in their twenties, whereas cervical cancers usually become evident in the fifth decade of life. The classic presentation of cervical malignancies includes abnormal bleeding and leukorrhea. The bleeding can range from blood streaking in a discharge or spotting to heavy bright red blood. Foul-smelling purulent leukorrhea is often present. Other symptoms, such as pelvic or leg pain, urinary or fecal material in the vagina, weight loss, and generalized weakness, are suggestive of advanced disease.

The squamocolumnar junction is where the squamous ectocervix abuts the columnar endocervix. Just distal to this junction there is an area of squamous metaplasia that is influenced by factors such menarche, pregnancy, local hormonal influences, infection, and trauma. As columnar epithelium is replaced by squamous cells, a new squamocolumnar junction is formed. The area between the old junction and the new junction is called the transformation zone. It is in this transformation zone that most cervical cancers arise.

Cervical cancer begins with infection of cervical epithelium by human papillomavirus. Most infections resolve spontaneously without progression to cancer. This suggests that viral infection alone is not responsible for cervical cancer and that other, undefined factors are involved in the pathogenesis. Additionally, there are many types of HPV that vary in oncogenic potential, with subtypes 16 and 18 being found most commonly in cervical caner.

Progression to dysplasia will occur if the viral genome is integrated into the nucleus of the cell under the influence of other factors that contribute to a favorable environment. Distinct cellular changes will occur, representing malignant transformation to low-grade cervical intraepithelial neoplasia (CIN I). A typical lesion will appear slightly raised or thickened with koilocytes in the upper and middle epithelial layers. Koilocytes are cells that have undergone cellular changes because of the presence of a virus. These cells are pleomorphic, hyperchromic, and multinucleated and have perinuclear halos. There are few if any mitotic figures and no atypical mitotic figures in CIN I, usually involving the lower third of the epithelium.

These low-grade CIN I lesions may regress spontaneously without treatment but may progress to higher-grade lesions. When atypical cells spread to between the lower 1/3 and 2/3 of the epithelium or the majority of the cells of the keratinizing layers, the lesion is defined as CIN II. These lesions demonstrate some areas of maturation but have areas of immature atypical koilocytic cells with a decreased nuclear to cytoplasmic ratio and increased numbers of mitotic figures (see Figure 9-2). Progression to CIN III involves the upper 1/3 of the epithelium by atypical cells with loss of maturation, an increase in hyperchromasia, and more mitotic figures with atypical mitoses. As the lesion progresses to squamous carcinoma in situ, the dysplastic cells may lose their cell walls and form syncytial-like groups. Many small round nuclei with scant cytoplasm can be seen. The majority of cells are atypical and are more hyperchromatic with coarse chromatin, a higher degree of pleomorphism, and increased atypical mitoses. Carcinoma in situ becomes invasive squamous cell carcinoma when atypical cells invade the basement membrane. Invasive carcinoma has wide variations of irregularly shaped cells and may have keratin pearls. There may also be evidence of necrosis, hemorrhage, and inflammatory cells.

The progression from CIN to cervical cancer is a slow process that usually occurs over several years. This allows many opportunities for screening before advanced-stage disease is evident. Most cases of cervical dysplasia are asymptomatic, and the diagnosis is made when a Pap smear reveals abnormal cytology. Good screening of asymptomatic patients, including a thorough history and physical, and routine Pap smears have led to a decreased incidence of cervical cancer. The role of the Pap smear is paramount in early detection of cervical dysplasia to afford timely treatment and avoid progression to invasive cervical cancer. Even after the development of cervical cancer, a Pap smear has an important role in detection because diagnosis early in the disease process may offer a better prognosis. Treatment of early cervical cancer offers a 95 percent cure rate, whereas more advanced stages often lead to death in more than a third of cases. This underscores the importance of diligent efforts by the physician in counseling patients to receive an annual Pap smear.

Figure 9-2. Microscopy of cervical dysplasia. (Courtesy of Dr. Margaret Uthman, Houston, TX.)0

COMPREHENSION QUESTIONS

[9.1] A 24-year-old woman is noted to have atypical cells on a Pap smear. Which of the following features most likely would indicate the need for further investigation of cervical biopsy?

A. HPV viral subtype revealing that type 16 is present

B. Presence of diabetes mellitus

C. Presence of endocervical cells

D. Presence of vulvar condylomata

E. Three lifetime sexual partners

[9.2] A 32-year-old woman is noted to have a 2-cm fungating lesion of the cervix. Which of the following is the best next step?

A. Application of tricyclic acetic acid (TCA)

B. Biopsy of the lesion

C. Pap smear of the cervix

D. Repeat examination after 6 months

[9.3] A hysterectomy specimen is performed, and the cervix is examined by the pathologist. The pathologist determines that the patient has CIN I. Which of the following is the most likely histologic finding?

A. Cells with enlarged nuclei and loss of polarity involving the upper third of the epithelium

B. Cells with enlarged nuclei involving the middle third of the epithelium

C. Cells with enlarged nuclei and loss of polarity involving the lower third of the epithelium

D. Cells with large nuclei and mitotic figures below the basement membrane but not more than 3 mm

ANSWERS

[9.1] A. In the Besthesda system of Papanicolau cytology reporting, findings can include atypical squamous cells of uncertain significance (ASCUS), low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, and invasive cancer. ASCUS does not necessarily translate into a serious condition, and some practitioners will repeat the Pap smear in 3 to 6 months. However, if a high-risk viral subtype such as 16 or 18 is detected, colposcopic examination with directed cervical biopsies is recommended to assess the extent of disease.

[9.2] B. The Pap smear is for cytologic analysis of a normal-appearing cervix and is used as a screening test. An abnormal cervix (i.e., lesion) should be biopsied.

[9.3] C. CIN I entails mild dysplasia that involves the lower third of the epithelium. Because the basal cells (those closest to the basement membrane) are the actively dividing cells, they are the ones affected by HPV.

PATHOLOGY PEARLS

· Cervical intraepithelial neopalsia is a precursor to cervical cancer.

· The vast majority of cases of cervical dyspasia and cancer are associated with human papillomavirus, particularly subtypes 16 and 18.

· The best method for analyzing a visible cervical lesion is biopsy, not a Pap smear.

· The Pap smear has decreased the incidence of cervical cancer in the United States dramatically.

· The Bethesda classification for pap smears reports atypical squamous cells of uncertain significance (ASCUS), low grade squamous intraepithelial lesion (LSIL), high grade squamous intraepithelial lesion (HSIL), and invasive cancer.

· LSIL includes human papilloma viral changes and CIN I.

· HSIL includes CIN II and CIN III and carcinoma in situ.

REFERENCES

Crum CP The female genital tract. In: Kumar V, Assas AK, Fausto N, eds. Robbins and Cotran pathologic basis of disease, 7 ed. Philadelphia: Elsevier Saunders, 2004:1072-1079.

DeCherney A, Lauren N. Current obstetric & gynecologic diagnosis and treatment, 9th ed. Chicago: Mcgraw-Hill, 2003.

Stenchever M, et al. Comprehensive gynecology, 4th ed. St. Louis: Mosby, 2001.

0.265625

Copyright © 2006 by the McGraw-Hill Companies, Inc. All rights reserved.