Paget's disease of the breast overview

Revision as of 17:33, 14 March 2019 by Preeti Singh (talk | contribs)
Jump to navigation Jump to search

Paget's disease of the breast Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Paget's disease of the breast from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Staging

History and Symptoms

Physical Examination

Biopsy

Ultrasonography

MRI

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Paget's disease of the breast overview On the Web

Most recent articles

cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Paget's disease of the breast overview

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Paget's disease of the breast overview

CDC on Paget's disease of the breast overview

Paget's disease of the breast overview in the news

Blogs on Paget's disease of the breast overview

Directions to Hospitals Treating Paget's disease of the breast

Risk calculators and risk factors for Paget's disease of the breast overview

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Suveenkrishna Pothuru, M.B,B.S. [2]

Overview

Paget's disease is an eczematous skin change of the nipple that is usually associated with an underlying breast malignancy. Paget's disease of the breast was first discovered by James Paget, a British surgeon and physiologist, in 1874.The characteristic erythema and eczematous changes of the nipple seen with Paget’s disease of the breast were first described by Velpeau in 1856. The correlation between intraductal cancer and Paget’s disease of the breast was by Jacobeus in 1904.The background for the epidermotropic theory, that ducts containing carcinoma cells were apparently connected to overlying nipples containing Paget’s cells, was demonstrated by Muir and Inglis in 1939 and 1946 respectively. The first case of Paget's disease in a male was described by Elbogen in 1908.. Paget's disease of the breast occurs in 1 – 4% of all female breast carcinoma cases. Paget's disease of the breast occurs in 0.5–5% of all breast cancer cases and is invariably associated with underlying malignancy either overt or occult. WHO revealed that there are 800,000 up to 1 million new cases of breast cancer each year. An underlying breast carcinoma is found in >90% of patients with Paget's disease. The majority of these cases are invasive disease although 40 – 45% are associated with ductal carcinoma in situ. Paget's disease of the breast is more prevalent in postmenopausal women, usually after the sixth decade of life, but it has also been reported in adolescent and elderly patients. Females are more commonly affected with Paget's disease of the breast than males. Male breast cancer accounts for less than 1% of all breast cancer and Paget's disease represents 1-3% of all breast malignancies. Mammary Paget's disease is almost always associated with an underlying breast cancer in 92–100% of cases. Approximately 50% of this patients present with an associated palpable mass in the breast. On microscopic histopathological analysis, epidermal Paget cells which are malignant glandular epithelial cells organized in groups with nest-like patterns or gland-like structures and are preferably located in the epidermal basal layer are characteristic findings of Paget's disease of the breast. Common risk factors in the development of Paget's disease of the breast are female more than male, incidence is higher with increase in age and people of African or Ashkenazi Jewish descent. Personal or family history of breast cancer Environmental exposure to radiation, high temperature and electromagnetic fields. Genetic mutations like BRCA1, BRCA2 4-14% of male breast cancer, klinefelter's syndrome in males. Mutations in RAD51B, PALB2, CYP17, CHEK2, BRIP1, RAD51C and androgen receptors. BRIP1 and RAD51C have not been seen in male patients. Endocrine-related states with hyperestrogenism such as obesity, exogenous estrogen, testicular dystrophic lesions in males. Symptoms of Paget's disease of the breast include itching, redness, thickened skin, and ulceration of the nipple. Common physical examination findings of Paget's disease of the breast include eczematous appearance of the nipple associated with yellowish or bloody discharge. Due to close similarity with many skin lesions, the diagnosis of Mammary Paget’s Diseas may be delayed or many cases can be misdiagnosed. Immunohistochemical staining for cytokeratin, epithelial membrane antigen (EMA) and c-erb-B2 oncoprotein is useful for the differential diagnosis. Toker cells found in the epidermis of the nipple, close to the opening of lactiferous ducts, along the basal layer of the epidermis, are morphologicaland immunohistochemical similar to mammary Paget's cells. In contrast to Paget's cells which are strongly associated with both Ki-67 and Her-2/c-erbB-2 and these markers are mostly used to distinguish Paget's cells from Toker cells. In case of atypical Toker cells a combination of CD138 and p53 is very helpful in distinguishing these atypical cells from Paget's cells. Paget's disease of the breast must be differentiated from atopic dermatitis, eczema, psoriasis, malignant melanoma, Bowen's disease, basal cell carcinoma, benign intraductal papilloma, nevoid hyperkeratosis of the nipple and areola (NHNA), squamous metaplasia of lactiferous ducts (SMOLD)/ Zuska's disease and pagetoid dyskeratosis. The prognosis for people with Paget's disease of the breast is primarily determined by the underlying tumor. Unfavorable prognosis is seen in cases with palpable breast tumor, enlarged lymph nodesand in patients younger than 60 years of age. Prognosis is worse in males than in females. Mean survival was found to be 80.0 months for males and 108.2 months for females. Five-year survival rate has been reported to be 20-30% in males, compared to 30-40% in females. This has been hypothesized to be due to the small size of mammary gland in males. Biopsy may be helpful in the diagnosis of Paget's disease of the breast. Mammogram may be performed to detect the breast cancer associated with Paget's disease of the breast. Mastectomy is the mainstay of treatment for Paget's disease of the breast. Adjunctive radiation may be required.



Historical Perspective

Paget's disease of the breast was first discovered by James Paget, a British surgeon and physiologist, in 1874.The characteristic erythema and eczematous changes of the nipple seen with Paget’s disease of the breast were first described by Velpeau in 1856. The correlation between intraductal cancer and Paget’s disease of the breast was by Jacobeus in 1904.The background for the epidermotropic theory, that ducts containing carcinoma cells were apparently connected to overlying nipples containing Paget’s cells, was demonstrated by Muir and Inglis in 1939 and 1946 respectively. The first case of Paget's disease in a male was described by Elbogen in 1908.

Classification

There is no classification system established for Paget's disease of the breast.

Pathophysiology

On gross pathology, eczematoid, erythematous, moist or crusted lesion, with or without fine scaling, infiltration of the nipple, and inversion of the nipple are characteristic findings of Paget's disease of the breast. Eczema changes of the nipple-areolar complex are said to occur due to invasion of the overlying epidermis by malignant (Paget) cells.The commonly accepted hypothesis is that most cases of Paget's disease of the breast originate from in situ or invasive ductal carcinoma of the underlying breast tissue. On microscopic histopathological analysis, epidermal Paget cells which are malignant glandular epithelial cells organized in groups with nest-like patterns or gland-like structures and are preferably located in the epidermal basal layer characteristic of Paget's disease of the breast.On gross pathology nipple and areola show eczematoid, erythematous, moist or crusted lesions, with or without fine scaling, infiltration of the nipple, and inversion of the nipple are characteristic findings of Paget's disease of the breast.Immunohistochemistry is very useful in Paget's disease of the breast for differential diagnoses and histogenesis. The overexpression of the low molecular weight cytokeratins, notably CK7, and lack of expression of high molecular weight cytokeratins, such as CK10, CK14 and CK20 are observed in 98-100% of Paget's disease of the Breast.

Causes

Mutations predisposing patients to Paget's disease of the breast have not yet been described in the literature.It is currently hypothesized that intraepidermal cells of Paget's disease may be intrinsically genetically different than those of the underlying breast carcinoma.This has been seen by specific chromosomal alterations identified by loss of heterozygosity and mitochondrial DNA displacement loop sequence analysis.The most widely accepted theory is that the disease results from an underlying intra-ductal breast carcinoma. The cancer cells are hypothesized to travel through lactiferous ducts to the nipple and its surrounding skin. Another theory is that the disease can develop independently in the nipple as an in-situ carcinoma.

Differential Diagnosis

Due to close similarity with many skin lesions, the diagnosis of Mammary Paget’s Diseas may be delayed or many cases can be misdiagnosed. Immunohistochemical staining for cytokeratin, epithelial membrane antigen(EMA) and c-erb-B2 oncoprotein is useful for the differential diagnosis. Toker cells found in the epidermis of the nipple, close to the opening of lactiferous ducts, along the basal layer of the epidermis, are morphologicaland immunohistochemical similar to mammary Paget's cells. In contrast to Paget's cells which are strongly associated with both Ki-67 and Her-2/c-erbB-2 and these markers are mostly used to distinguish Paget's cells from Toker cells. In case of atypical Toker cells a combination of CD138 and p53 is very helpful in distinguishing these atypical cells from Paget's cells. Paget's disease of the breast must be differentiated from atopic dermatitis, eczema, psoriasis, malignant melanoma, Bowen's disease, basal cell carcinoma, benign intraductal papilloma, nevoid hyperkeratosis of the nipple and areola (NHNA), squamous metaplasia of lactiferous ducts (SMOLD)/ Zuska's disease and pagetoid dyskeratosis.

Epidemiology and Demographics

Paget's disease of the breast occurs in 0.5–5% of all breast cancer cases and is invariably associated with underlying malignancy either overt or occult. WHO revealed that there are 800,000 up to 1 million new cases of breast cancer each year. An underlying breast carcinoma is found in >90% of patients with Paget's disease. The majority of these cases are invasive disease although 40 – 45% are associated with ductal carcinoma in situ. Paget's disease of the breast is more prevalent in postmenopausal women, usually after the sixth decade of life, but it has also been reported in adolescent and elderly patients. Females are more commonly affected with Paget's disease of the breast than males. Male breast cancer accounts for less than 1% of all breast cancer and Paget's disease represents 1-3% of all breast malignancies.

Risk Factors

Common risk factors in the development of Paget's disease of the breast are female more than male, incidence is higher with increase in age and people of African or Ashkenazi Jewish descent. Personal or family history of breast cancer Environmental exposure to radiation, high temperature and electromagnetic fields. Genetic mutations like BRCA1, BRCA2 4-14% of male breast cancer, klinefelter's syndrome in males. Mutations in RAD51B, PALB2, CYP17, CHEK2, BRIP1, RAD51C and androgen receptors. BRIP1 and RAD51C have not been seen in male patients. Endocrine-related states with hyperestrogenism such as obesity, exogenous estrogen, testicular dystrophic lesions in males.

Screening

According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for Paget's disease of the breast.[1]

Natural History, Complications and Prognosis

The prognosis for people with Paget's disease of the breast is primarily determined by the underlying tumor. Unfavorable prognosis is seen in cases with palpable breast tumor, enlarged lymph nodesand in patients younger than 60 years of age. Prognosis is worse in males than in females. Mean survival was found to be 80.0 months for males and 108.2 months for females. Five-year survival rate has been reported to be 20-30% in males, compared to 30-40% in females. This has been hypothesized to be due to the small size of mammary gland in males.

Diagnosis

Staging

There is no established system for the staging of Paget's disease of the breast. REDIRECT Breast cancer staging

History and Symptoms

Symptoms of Paget's disease of the breast include itching, redness, thickened skin, and ulceration of the nipple.

Physical Examination

Common physical examination findings of Paget's disease of the breast include eczematous appearance of the nipple associated with yellowish or bloody discharge.

Biopsy

Biopsy may be helpful in the diagnosis of Paget's disease of the breast. Findings on biopsy diagnostic of Paget's disease of the breast include presence of Paget cells, which are arranged in solid groups.[2]

Ultrasonography

Ultrasonography of the breast may be performed to detect the breast cancer associated with Paget's disease of the breast.

MRI

MRI may be performed to detect the breast cancer associated with Paget's disease of the breast.

Other Imaging Findings

Mammogram may be performed to detect the breast cancer associated with Paget's disease of the breast.

Other Diagnostic Studies

No additional tests are recommended for the diagnosis of Paget's disease of the breast.

Treatment

Medical Therapy

The predominant therapy for Paget's disease of the breast is surgical resection. Adjunctive radiation may be required.

Surgery

Mastectomy is the mainstay of treatment for Paget's disease of the breast. Patients who do not have a palpable lump are treated with removal of the nipple and areola, followed by whole-breast radiation therapy, whereas patients with associated ductal carcinoma in situ or invasive breast cancer are treated with complete resection of the underlying disease with excision of the nipple-areola complex and radiation therapy of the remaining breast tissue. When lymph nodes are involved, more extensive axillary lymph node surgery may be needed.

References

  1. Paget's disease of the breast. U.S. Preventive Services Task Force.http://www.uspreventiveservicestaskforce.org/BrowseRec/Search?s=breast+cancer
  2. Lopes Filho, Lauro Lourival; Lopes, Ione Maria Ribeiro Soares; Lopes, Lauro Rodolpho Soares; Enokihara, Milvia M. S. S.; Michalany, Alexandre Osores; Matsunaga, Nobuo (2015). "Mammary and extramammary Paget's disease". Anais Brasileiros de Dermatologia. 90 (2): 225–231. doi:10.1590/abd1806-4841.20153189. ISSN 1806-4841.


Template:WikiDoc Sources