This document discusses various types of polyps that can occur in the gastrointestinal tract, including hamartomatous, hyperplastic, inflammatory, and neoplastic polyps. It provides details on several polyposis syndromes where multiple polyps are present, such as Peutz-Jeghers syndrome, Cowden syndrome, familial adenomatous polyposis, and hereditary non-polyposis colorectal cancer. The document compares the clinical features, pathogenesis, morphology, and cancer risks associated with different polyp types and syndromes.
Non–small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Histologically, NSCLC is divided into adenocarcinoma, squamous cell carcinoma (SCC) (see the image below), and large cell carcinoma. Small cell lung cancer (SCLC), previously known as oat cell carcinoma, is considered distinct from other lung cancers, which are called non–small cell lung cancers (NSCLCs) because of their clinical and biologic characteristics.
Presentation about lipoma and liposarcoma, origin, cause, description, diagnosis, treatment with pictures that help the better understanding of the topic.
Non–small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Histologically, NSCLC is divided into adenocarcinoma, squamous cell carcinoma (SCC) (see the image below), and large cell carcinoma. Small cell lung cancer (SCLC), previously known as oat cell carcinoma, is considered distinct from other lung cancers, which are called non–small cell lung cancers (NSCLCs) because of their clinical and biologic characteristics.
Presentation about lipoma and liposarcoma, origin, cause, description, diagnosis, treatment with pictures that help the better understanding of the topic.
Presentation about the the second most common type of ovarian tumors which have a very unique property of being similar to the testicular germ cell tumors.
Thyroid Pathologies- Introduction, Benign diseases and Carcinoma ThyroidSelvaraj Balasubramani
Dear Viewers,
Greetings from " Surgical Educator"
I have uploade a PPT presentation consist of Introduction, Benign diseases and Carcinoma Thyroid. By watching the accompanying video and reading the PPT, you will become competent in diagnosing and treating any thyroid pathologies.
you can watch my surgery teaching videos in the following links
youtube.com/c/surgicaleducator
surgicaleducator.blogspot.com
Thank you.
Brief description on the benign tumors of liver that includes hemangioma, focal nodular hyperplasia, regenerative nodular hyperplasia, dysplastic foci, dysplastic nodules and focal fatty change.
Testicular tumors are rare.
1 – 2 % of all malignant tumors.
Most common malignancy in men in the 15 to 35 year age group.
Benign lesions represent a greater percentage of cases in children than in adults.
Most curable solid neoplasm
there is the introduction part of the torso trauma,
check out my next ppts for further more about torso trauma.
contents are in following order...
introduction
mechanism of injury
junctional zones of torso
tension pneumothorax
cardiac temponade
massive hemothorax
etc.
check out all slides
Like the playlist in YouTube, in this presentation I have combined three of my presentation into one for the benefit of medical students and surgical trainees. The first presentation regading introduction to breast pathologies, second regarding benign breast lesions and the third one is regarding Carcinoma Breast. Hope you will enjoy this.
Presentation about the the second most common type of ovarian tumors which have a very unique property of being similar to the testicular germ cell tumors.
Thyroid Pathologies- Introduction, Benign diseases and Carcinoma ThyroidSelvaraj Balasubramani
Dear Viewers,
Greetings from " Surgical Educator"
I have uploade a PPT presentation consist of Introduction, Benign diseases and Carcinoma Thyroid. By watching the accompanying video and reading the PPT, you will become competent in diagnosing and treating any thyroid pathologies.
you can watch my surgery teaching videos in the following links
youtube.com/c/surgicaleducator
surgicaleducator.blogspot.com
Thank you.
Brief description on the benign tumors of liver that includes hemangioma, focal nodular hyperplasia, regenerative nodular hyperplasia, dysplastic foci, dysplastic nodules and focal fatty change.
Testicular tumors are rare.
1 – 2 % of all malignant tumors.
Most common malignancy in men in the 15 to 35 year age group.
Benign lesions represent a greater percentage of cases in children than in adults.
Most curable solid neoplasm
there is the introduction part of the torso trauma,
check out my next ppts for further more about torso trauma.
contents are in following order...
introduction
mechanism of injury
junctional zones of torso
tension pneumothorax
cardiac temponade
massive hemothorax
etc.
check out all slides
Like the playlist in YouTube, in this presentation I have combined three of my presentation into one for the benefit of medical students and surgical trainees. The first presentation regading introduction to breast pathologies, second regarding benign breast lesions and the third one is regarding Carcinoma Breast. Hope you will enjoy this.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
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2. What are the possibilities?
A 59-year-old woman presented with: h/o
20-year history of papules on the dorsa of the hands and
feet
Benign tumor of the breast at age 16
Bone cyst of the femur at age 21
Breast cancer at age 45
At age 46, she developed hyperthyroidism
Breast cancer in the contralateral breast at age 52
Five years later, bilateral partial nephrectomies were
performed for renal cell carcinoma
3. What is the abnormality?
What is your suspicion?
4. What is the abnormality?
What is your diagnosis?
5. What is the abnormality?
What is your diagnosis?
6. Some questions
• What is the important criterion in the
definition of adenoma in GIT?
• What is a Hamartoma?
• What do you understand by the term
familial?
• How do you define a polyp?
• How a polyp is different from adenoma?
• What do you understand by the terms:
– Sessile
– Pedunculated
13. Histologic features - SRU
• Mucosal prolapse and include lamina propria
• Fibromuscular hyperplasia
• Mixed inflammatory infiltrates
• Erosion and epithelial hyperplasia
15. HAMARTOMATOUS POLYPS
• Occurrence:
– Sporadically or
– As components of Syndromes
• Rare
• Importance:
– Intestinal and extra-intestinal manifestations
– May be present in other family members
21. Peutz-Jeghers Syndrome
• AD
• Age of presentation: ~11yrs
• Multiple polyps and mucocutaneous
hyperpigmentation
• Increased risk for several malignancies
– colon, pancreas, breast, lung, ovaries, uterus,
and testicles, sex cord tumors
23. Peutz-Jeghers Syndrome
Pathogenesis:
• LOH of tumor suppressor gene
LKB1/STK11
– LKB1/STK11 is a kinase that regulates cell
polarization, growth, and metabolism
• Polyps in PJ syndrome:
– Are not premalignant
– Adenocarcinomas arise independently
24. Peutz-Jeghers Syndrome
• Barium enema
radiograph showing
multiple polyps
(mostly pedunculated)
and at least one large
mass at the hepatic
flexure coated with
contrast in a patient
with Peutz–Jeghers
syndrome.
26. Morphology
• Hamartomatous polyp
• Arborizing network of
connective tissue,
smooth muscle, lamina
propria
• Glands lined by
normal-appearing
intestinal epithelium
27. DD - Polyps of
PJ syndrome from Juvenile polyps
• The arborization and presence of smooth
muscle intermixed with lamina propria are
helpful in distinguishing polyps of Peutz-
Jeghers syndrome from juvenile polyps
28. Peutz-Jeghers Syndrome
Diagnosis:
– Multiple polyps in the small intestine
– Mucocutaneous hyperpigmentation &
– Positive family history
– Detection of LKB1/STK11 mutations
Surveillance:
– There is increased risk of cancer
– Routine surveillance of the GI tract, pelvis,
and gonads is recommended
29. Peutz-Jeghers Syndrome
Because of the increased risk of cancer,
routine surveillance of the GI tract, pelvis,
and gonads is typically recommended
30. Cowden Syndrome
• AD
• Hamartomatous polyps
• Loss-of-function mutations in PTEN
• Characterized by:
– Macrocephaly
– Intestinal hamartomatous polyps
– Benign skin tumors
• Increased risk of GI malignancy
• Other cancers:
– Breast carcinoma
– Follicular carcinoma of the thyroid and
– Endometrial carcinoma
32. HYPERPLASTIC POLYPS
• Sixth and seventh decades
• Result from decreased epithelial cell
turnover and delayed shedding of surface
epithelial cells
• No malignant potential
• Importance: they must be distinguished
from sessile serrated adenomas,
histologically similar lesions that have
malignant potential
34. Hyperplastic polyp
• A: Polyp surface with
irregular tufting of
epithelial cells
• B: Tufting results from
epithelial overcrowding
• C: Epithelial crowding
produces a serrated
architecture when
glands are cut in cross-
section
36. NEOPLASTIC POLYPS
Colonic adenomas:
• Characterized by the presence of epithelial dysplasia
• Importance: precursors to colorectal adenocarcinomas
• Small, pedunculated polyps / large sessile lesions
• Clinical Features:
– Most adenomas are clinically silent
– Large polyps may produce occult bleeding and anemia
– Villous adenomas that cause hypoproteinemic
hypokalemia
37. Adenoma - Morphology
Gross:
•Size: 0.3 to 10 cm in diameter
•Pedunculated or Sessile
•Velvetty surface
Histology:
•Dysplasia (Hyperchromatic nuclei,
stratification, large nucleoli, reduced number
of goblet cells)
38. • Adenomas can be classified as:
(Architectural)
– Tubular
– Villous or
– Tubulovillous
39. Tubular adenomas
• Small
• Pedunculated polyps
• Histology: composed of small rounded,
or tubular, glands
53. Villous adenomas with adenocarcinoma
Note: Villous architecture alone does not increase cancer
risk when polyp size is considered
54. Sessile serrated adenomas
• Overlap histologically with hyperplastic polyps
• More commonly found in the right colon
• High malignant potential
• They lack features of dysplasia
• Histology:
– Serrated architecture throughout the full length of the
glands
– Lateral growth and crypt dilation
– DD: Hyperplastic polyp: Serrated architecture is
typically confined to the surface
58. Adenomas - Risk of malignancy
• Most colorectal adenomas are benign
• Risk factors for malignancy:
– Number of adenomas
– Size is the most important characteristic that
correlates with risk of malignancy
• Adenomas <1 cm in diameter – BENIGN
• Adenomas > 4 cm in diameter – May contain Malignancy
– High-grade dysplasia increases the risk in that
polyp
62. FAMILIAL ADENOMATOUS POLYPOSISFAMILIAL ADENOMATOUS POLYPOSIS
• AD
• Manifests in teenage
• Numerous colonic polyps
– At least 100 polyps are necessary for a
diagnosis of classic FAP
• Polyps are morphologically similar to
sporadic adenomas
64. Importance: if untreated
– Colorectal adenocarcinoma - 100%
– Often before age 30yrs
Note: Prophylactic colectomy is the standard
therapy for individuals carrying APC
mutations
65. Colectomy and Malignancy
• Colectomy prevents colorectal cancer
• Risk for neoplasia at other sites remains
unchanged
– Eg: Adenomas may develop elsewhere in the
GI tract, particularly adjacent to the ampulla of
Vater and in the stomach
66. Variants of FAP
• Specific APC mutations have been
associated with the development of other
manifestations of FAP
– Gardner syndrome
– Turcot syndrome
69. HEREDITARY NON-POLYPOSIS
COLORECTAL CANCER - HNPCC
• Synonym: Lynch syndrome
• Familial clustering of cancers at several sites:
– Colorectum (at younger ages)
– Stomach
– Small bowel
– Hepatobiliary tract
– Endometrium
– Ovary
– Ureters
– Brain and
– Skin
70. HEREDITARY NON-POLYPOSIS
COLORECTAL CANCER - HNPCC
Genetic defect:
•Defective DNA mismatch repair genes
•There are five such mismatch repair genes
– Majority of HNPCC cases involve MSH2 and MLH1
Cowden&apos;s syndromeOlympia Kovich MD, and David Cohen MD MPH Dermatology Online Journal 10 (3): 3
From the Ronald O. Perelman Department of Dermatology, New York University
Dermatology online Journal
&lt;https://escholarship.org/uc/item/6bp1n1k3Cowden&gt;
PJ syndrome.
Gardner syndrome:
Polyposis coli
Osteomas
People with Turcot syndrome have multiple adenomatous colon polyps (polyps in the colon made up of cells that form mucous), an increased risk of colorectal cancer, and an increased risk of brain cancer (Medulloblastoma).
The two most common types of brain tumors in Turcot syndrome are:
Glioblastoma. This type of brain tumor is a very aggressive form of astrocytoma that is commonly found in families who have features of HNPCC.
Medulloblastoma. This type of brain tumor begins in granular cells in the cerebellum (back of the brain). Medulloblastoma most often occurs in children and is commonly found in families who have features of FAP.
These are referred to as sessile, a term borrowed from botanists who use it to describe flowers and leaves that grow directly from the stem without a stalk. As sessile polyps enlarge, several processes, including proliferation of cells adjacent to the mass and the effects of traction on the luminal protrusion, may combine to create a stalk. Polyps with stalks are termed pedunculated. In general, intestinal polyps can be classified as non-neoplastic or neoplastic in nature.
FIGURE 17-41 Solitary rectal ulcer syndrome. A, The dilated glands, proliferative epithelium, superficial erosions, and inflammatory infiltrate are typical of an inflamatory polyp. However, the smooth muscle hyperplasia within the lamina propria suggests that mucosal prolapse has also occurred. B, Epithelial hyperplasia. C, Granulation tissue-like capillary proliferation within the lamina propria caused by repeated erosion and re-epithelialization.
Hamatoma: Hamartomas are tumor-like growths composed of mature tissues that are normally present at the site in which they develop.
Although hamartomatous polyposis syndromes are rare, they are important to recognize because of associated intestinal and extra-intestinal manifestations and the possibility that other family members are affected.
FIGURE 17-42 Juvenile polyposis. A, Juvenile polyp. Note the surface erosion and cystically dilated crypts. B, Inspissated mucous, neutrophils, and inflammatory debris can accumulate within dilated crypts.
Although the morphogenesis of juvenile polyps is incompletely understood, some have suggested that mucosal hyperplasia is the initiating event. This hypothesis is consistent with the discovery that mutations in pathways that regulate cellular growth cause autosomal dominant juvenile polyposis. The most common mutation identified is of SMAD4, which encodes a cytoplasmic intermediate in the TGF-β signaling pathway. BMPR1A, a kinase that is a member of the TGF-β superfamily, may be mutated in other cases (see Table 17-9 ). However, these mutations account for fewer than half of patients, suggesting that changes in other genes can also cause juvenile polyposis. Dysplasia occurs in a small proportion of juvenile polyps, and the juvenile polyposis syndrome is associated with an increased risk of colonic adenocarcinoma.
Peutz-Jeghers Syndrome, An Overview
Introduction
In the 1920s and 1930s two physicians on opposite sides of the Atlantic ocean published and reviewed case reports about individuals with distinctive mucosal and skin pigment lesions and concurrently had intestinal polyps.[1] Often these individuals were members of the same family. The complex of skin and mucosal pigment abnormalities and associated intestinal polyps would later bare their names, the Peutz-Jeghers Syndrome.
Dr. Harold Jeghers of the United States and Dr. Johannes Peutz of Holland [2] and subsequent investigators of the Peutz-Jeghers Syndrome recognized that these mucocutaneous pigment lesions and concurrent gastrointestinal polyps &quot;must be due to the presence of a single pleiotropic gene, responsible for both characteristics, the polyps and the spots.&quot;[3] With the passage of time and continued observations, medical investigators realized that individuals with these clinical findings were at increased risk for neoplasias and a life shortened by cancer.
Discovery
The syndrome now characterized at the molecular level; had its beginnings in case reports as early as the 1890s.[4,5] One early report by Dr. Peutz dating back to the winter of 1920 described a 15 year old boy with anorexia, nausea, abdominal pain, weight loss and distinctive pigmentation on his face. Dr. Peutz recalled treating this patient&apos;s brother the previous summer. Other family members were found to have abnormalities associated with the syndrome. Four siblings had pigment lesions of the mucosa and three members had intestinal polyposis, while two had nasal polyposis.[3]
Dr. Jeghers&apos; contribution to the understanding of this syndrome came through his studies of prior published cases and his subsequent publication of followup evaluations. His use of a personal medical library, served him in retrieving prior case reports which he used in his review and analysis. Although Dr. Jeghers&apos; studies in the 1940s lacked the statistical rigor of current analyses of the medical literature, his use of the literature in tracking prior cases was unusual for its time. He identified a case report from a 1895 publication, describing 12 year old identical twin sisters having dark pigmented lips, gums and hard palate.[4] He subsequently obtained followup history of these two individuals. His use of a personal library demonstrated the value of researching medical literature.
Clinical Findings
The early case reports of the 1920s and 1930s described intussusceptions, a form of intestinal blockage, and gastrointestinal bleeding as complications of this syndrome. As case reports and case studies accumulated throughout the 1950s and 1970s, the association of malignancies as part of the Peutz-Jeghers Syndrome evolved. The intestinal polyps associated with the Peutz-Jeghers Syndrome, described as hamartomatous in nature and their occurrence in unusual sites such as the jejunum, mark the individual as being at increased risk for developing a cancer. Although initially characterized as a syndrome associated with gastrointestinal polyps and other gastrointestinal neoplasms, clinicians have come to realize that tumors of the extra-intestinal organ systems could also develop.
Conclusion
Much has been learned over the past decades about the Peutz-Jeghers Syndrome. The benign nature of the skin and mucosal findings belie the more sinister nature of the syndrome&apos;s malignant predisposition. In recent times the Peutz-Jeghers Syndrome has become the focus of molecular genetic studies.
The ease with which international collaboration regarding medical matters occurs today is a far cry from that existing in the era of Drs. Jeghers and Peutz. The understanding of the Peutz-Jeghers Syndrome which evolved over decades would today most probably occur in months. Peutz-Jeghers Syndrome is thoroughly described in medical publications and is recognized as occurring in the world&apos;s population.
1. Keller JJ, Offerhaus GJ, Giardiello FM, Menko FH. Jan Peutz, Harold Jeghers and a remarkable combination of polyposis and pigmentation of the skin and mucous membranes. Fam. Cancer 2002 1:181-185.
2. Peutz, JL. Very remarkable case of familial polyposis of mucous membrane of intestinal tract and nasopharynx accompanied by peculiar pigmentations of skin and mucous membrane. (Dutch). Nederl. Maandschr. Geneesk. 1921 10:134-146.
3. Jeghers H, McKusick VA, Katz, KH. Generalized intestinal polyposis and melanin spots of the oral mucosa, lips and digits. N Engl J Med. 1949 Dec 22;241(25):993, illust; passim. Large file (4 MB)
4. Connor JT.Aesculapian Society of London.Lancet 1895 2:1169.
5. Hutchinson, J. : Pigmentation of lips and mouth. Arch. Surg. 1896 7:290-1.
PJ-Syndrome: This rare autosomal dominant syndrome presents at a median age of 11 years with multiple GI hamartomatous polyps and mucocutaneous hyperpigmentation. The latter takes the form of dark blue to brown macules around the mouth, eyes, nostrils, buccal mucosa, palmar surfaces of the hands, genitalia, and perianal region. These lesions are similar to freckles but are distinguished by their presence in the buccal mucosa. Peutz-Jeghers polyps can initiate intussusception, which is occasionally fatal. Of greater importance, Peutz-Jeghers syndrome is associated with an increased risk of several malignancies, including cancers of the colon, pancreas, breast, lung, ovaries, uterus, and testicles, as well as other unusual neoplasms, such as sex cord tumors.
Pathogenesis.
Germline heterozygous loss-of-function mutations in the gene LKB1/STK11 are present in approximately half of individuals with familial Peutz-Jeghers syndrome as well as a subset of patients with sporadic PeutzJeghers syndrome. LKB1/STK11 is a kinase that regulates cell polarization, growth, and metabolism. The function of the second “normal” copy of LKB1/STK11 is often lost through somatic mutation in cancers occurring in Peutz-Jeghers syndrome, consistent with the view that LKB1/STK11 is a tumor suppressor gene and providing an explanation for the high risk of neoplasia in affected patients. The GI adenocarcinomas arise independently of the hamartomatous polyps, indicating that the hamartomas are not preneoplastic precursor lesions.
Pathogenesis.
Germline heterozygous loss-of-function mutations in the gene LKB1/STK11 are present in approximately half of individuals with familial Peutz-Jeghers syndrome as well as a subset of patients with sporadic PeutzJeghers syndrome. LKB1/STK11 is a kinase that regulates cell polarization, growth, and metabolism. The function of the second “normal” copy of LKB1/STK11 is often lost through somatic mutation in cancers occurring in Peutz-Jeghers syndrome, consistent with the view that LKB1/STK11 is a tumor suppressor gene and providing an explanation for the high risk of neoplasia in affected patients. The GI adenocarcinomas arise independently of the hamartomatous polyps, indicating that the hamartomas are not preneoplastic precursor lesions.
Morphology. The polyps of Peutz-Jeghers syndrome are most common in the small intestine, although they may occur in the stomach and colon, and, with much lower frequency, in the bladder and lungs. Grossly, the polyps are large and pedunculated with a lobulated contour. Histologic examination demonstrates a characteristic arborizing network of connective tissue, smooth muscle, lamina propria, and glands lined by normal-appearing intestinal epithelium ( Fig. 17-43 ). The arborization and presence of smooth muscle intermixed with lamina propria are helpful in distinguishing polyps of Peutz-Jeghers syndrome from juvenile polyps.
FIGURE 17-43 Peutz-Jeghers polyp. A, Polyp surface (top) overlies stroma composed of smooth muscle bundles cutting through the lamina propria. B, Complex glandular architecture and the presence of smooth muscle are features that distinguish Peutz-Jeghers polyps from juvenile polyps. Compare to Figure 17-42 .
Papules on the nose
Filiform papule on the right nasolabial fold
FIGURE 17-45 Colonic adenomas. A, Pedunculated adenoma (endoscopic view). B, Adenoma with a velvety surface. C, Low-magnification photomicrograph of a pedunculated tubular adenoma
FIGURE 17-47 Adenoma with intramucosal carcinoma. A, Cribriform glands interface directly with the lamina propria without an intervening basement membrane. B, Invasive adenocarcinoma (left) beneath a villous adenoma (right). Note the desmoplastic response to the invasive components.
Sessile serrated adenomas overlap histologically with hyperplastic polyps, but are more commonly found in the right colon.[110] Despite their malignant potential, sessile serrated adenomas lack typical cytologic features of dysplasia that are present in other adenomas ( Fig. 17-46C ). Histologic criteria include serrated architecture throughout the full length of the glands, including the crypt base, associated with lateral growth and crypt dilation ( Fig. 17-46D ). In contrast, serrated architecture is typically confined to the surface of hyperplastic polyps.
FIGURE 17-46 Histologic appearance of colonic adenomas. A, Tubular adenoma with a smooth surface and rounded glands. Active inflammation is occasionally present in adenomas, in this case, crypt dilation and rupture can be seen at the bottom of the field. B, Villous adenoma with long, slender projections that are reminiscent of small intestinal villi. C, Dysplastic epithelial cells (top) with an increased nuclear-to-cytoplasmic ratio, hyperchromatic and elongated nuclei, and nuclear pseudostratification. Compare to the nondysplastic epithelium below. D, Sessile serrated adenoma lined by goblet cells without typical cytologic features of dysplasia. This lesion is distinguished from a hyperplastic polyp by extension of the neoplastic process to the crypts, resulting in lateral growth. Compare to the hyperplastic polyp in Figure 17-44A
Although most colorectal adenomas are benign lesions, a small proportion may harbor invasive cancer at the time of detection. Size is the most important characteristic that correlates with risk of malignancy. For example, while cancer is extremely rare in adenomas less than 1 cm in diameter, some studies suggest that nearly 40% of lesions larger than 4 cm in diameter contain foci of cancer. In addition to size, high-grade dysplasia is a risk factor for cancer in an individual polyp (but not other polyps in the same patient).
FIGURE 17-48 Familial adenomatous polyposis. A, Hundreds of small polyps are present throughout this colon with a dominant polyp (right). B, Three tubular adenomas are present in this single microscopic field.
FAP is associated with a variety of extra-intestinal manifestations including congenital hypertrophy of the retinal pigment epithelium, which can generally be detected at birth and can be an adjunct to early screening. Specific APC mutations have been associated with the development of other manifestations of FAP and explain variants such as Gardner syndrome and Turcot syndrome. In addition to intestinal polyps, Gardner syndrome families have osteomas of mandible, skull, and long bones, epidermal cysts, desmoid tumors, thyroid tumors, and dental abnormalities, including unerupted and supernumerary teeth. Turcot syndrome is rarer and characterized by intestinal adenomas and tumors of the central nervous system. Two thirds of patients with Turcot syndrome have APC gene mutations and develop medulloblastomas. The remaining one third have mutations in one of several genes involved in DNA repair and develop glioblastomas.
Some FAP patients without APC loss have mutations of the base-excision repair gene MUTYH.[112] The role of these genes in tumor development is discussed below. In addition, certain APC and MUTYH mutations are associated with attenuated forms of FAP, which are characterized by delayed polyp development, the presence of fewer than 100 adenomas, and the delayed appearance of colon cancer, often to ages of 50 or above.[113]
Polyposis coli
Osteomas
People with Turcot syndrome have multiple adenomatous colon polyps (polyps in the colon made up of cells that form mucous), an increased risk of colorectal cancer, and an increased risk of brain cancer (Medulloblastoma).
The two most common types of brain tumors in Turcot syndrome are:
Glioblastoma. This type of brain tumor is a very aggressive form of astrocytoma that is commonly found in families who have features of HNPCC.
Medulloblastoma. This type of brain tumor begins in granular cells in the cerebellum (back of the brain). Medulloblastoma most often occurs in children and is commonly found in families who have features of FAP.