College of American Pathologists
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  Metaplastic Breast Carcinoma


CLINICAL SUMMARY: A 32-year-old previously healthy woman noted a reddish, scaling area of skin over her left breast that enlarged over 3 months. For the past month, she noted the presence of tender nodules beneath the skin of her abdomen. On physical examination she had an irregular 5 cm area of red-orange, rough, firm skin over the lower outer quadrant of her left breast; overlying an ill-defined mass. Laboratory studies showed total serum protein 5.4 g/dL (normal 6.3-8.2 g/dL), albumin 3.2 g/dL (normal 3.5-5.2 g/dL), alkaline phosphatase 88 U/L (normal 45-150 U/L), total bilirubin 1.1 mg/dL (normal 0-1.5 mg/dL), AST 1023 U/L (normal 15-50 U/L), and ALT 1112 U/L (normal 6-50 U/L). Her prothrombin time was 12 seconds with INR 1.0 and partial thromboplastin time 29 seconds (normal 25-35 seconds). A CBC showed Hgb 12.0 g/dL, Hct 35.8%, MCV 86 fL, WBC count 6740/ mm3, and platelet count 199,200/mm.3 A breast biopsy was performed. When informed of the diagnosis she declined treatment. She developed worsening chest and abdominal pain over the next 2 weeks. Three weeks following the biopsy she experienced the sudden onset of acute chest pain with severe dyspnea, and a chest CT scan showed the findings [AU-01 (J)]. Although she survived this episode, her affect became increasingly blunted, her mood sad, her speech slowed, and she began sleeping up to 20 hours per day. A month later she entered hospice care. She received opiates for pain management. She developed the sudden onset of acute chest pain with severe dyspnea two weeks following the beginning of hospice care and died an hour later. An autopsy consent was obtained from her mother (the deceased had been married but divorced, and her only child was an 11-year-old daughter). The autopsy consent excluded examination of the brain but allowed retention of organs for diagnosis and teaching. Following the autopsy the deceased’s mother asked for counseling in regard to the results of the autopsy.

AUTOPSY FINDINGS: The gross appearance of the left breast is shown in AU-01 (A). Sections of the left breast are shown in AU-01 (B, C). Microscopic sections of skin and breast are shown in AU-01 (D-F). On opening the thoracic cavity there was 500 mL on the left and 600 mL on the right of cloudy, yellow fluid in the pleural spaces. The heart weighed 340 grams and had minimal coronary atherosclerosis with no occlusion. On opening the abdomen there was 1400 mL of slightly cloudy, yellow fluid within the peritoneal cavity. The liver weighed 1650 grams and had the appearance shown in AU-01 (G, H). The spleen weighed 400 grams. A thrombus was present in the right femoral vein.

Questions and Discussion: (correct response is underlined)

1. What is most likely to account for the gross and microscopic appearances of the skin overlying the breast? Respondents
No. %
Lymphatic involvement by carcinoma 150 100.0
Chronic myelogenous leukemia - -
Intraductal papillomas - -
Staphylococcus aureus infection - -
Thrombophlebitis - -

2. Which of the following is the most likely diagnosis for her breast mass? Respondents
No. %
Metaplastic carcinoma 128 85.3
Inflammatory carcinoma 22 14.7
Intraductal carcinoma - -
Medullary carcinoma - -
Metastatic carcinoma - -

The underlying cause of death in this case is breast carcinoma. This carcinoma has a prominent “inflammatory” component from involvement of dermal lymphatic channels by the carcinoma. “Inflammatory” carcinoma is not a specific histologic type of breast carcinoma, but merely a descriptive term. Lymphatic invasion results in induration and erythema of the skin that suggests inflammation. The grossly thickened, roughened, and red to orange appearance may resemble eczema, and is sometimes described by Francophiles as a “peau d’orange” (orange peel) appearance. Carcinomas underlying this inflammatory component tend to be highly infiltrative and may not form a discrete mass, as shown in AU-01 (B).1,2

Though leukemic infiltrates may produce vascular occlusion, the cells in this case are typical for carcinoma, and this patient’s WBC count was not in the very high range seen with chronic myelogenous leukemia or other leukemias associated with leukostasis. Intraductal papillomas are benign lesions that may be seen within breast lactiferous sinuses and large ducts, often beneath the nipple, and are not intravascular. Mastitis is most often a complication of lactation and S. aureus is the most common infectious organism, but the inflammation typically involves the underlying breast ducts and includes pronounced inflammatory infiltrates, not carcinoma.

Thrombophlebitis of the breast (Mondor disease) can produce focal swelling and pain, but thrombi are not seen in this patient’s breast.1

The histologic features of the breast mass as shown in AU-01 (C, D) suggest squamous differentiation, with large cells having distinct cell borders, prominent pink cytoplasm, and a growth pattern in nests or whorls. Such a pattern can be seen with “metaplastic carcinoma” of the breast. Less than 1% of breast cancers have metaplastic components. Metaplastic breast cancers contain epithelial and/or mesenchymal components. The epithelial component most often consists of ductal carcinoma but may also include squamoid, medullary, mucinous, or apocrine patterns. The mesenchymal components can include fibrosarcomatous, cartilaginous, muscular, osseous, or vascular differentiation, but sometimes consists solely of poorly differentiated spindle cells.1,3,4

Though intraductal carcinoma may be extensive, there is no defined mass, and the lack of an invasive component precludes lymphatic involvement. A medullary carcinoma typically appears as a large, well-circumscribed mass that microscopically consists of large, pleomorphic cells in a prominent lymphoplasmacytic infiltrate. The findings in this case, particularly with the dermal lymphatic invasion, are most consistent with a breast primary and not metastases from elsewhere.1

3. Which one of the following processes is shown in the liver? Respondents
No. %
Budd-Chiari syndrome 136 91.3
Veno-occlusive disease 13 8.7
Banti syndrome - -
Caroli disease - -
Peliosis hepatis - -

The liver has a large thrombus occluding the hepatic venous outflow, consistent with Budd-Chiari syndrome. Note the presence of metastatic tumor nodules as well. Findings with Budd-Chiari syndrome may include abdominal pain, hepatic enlargement, and ascites. The blockage of the hepatic veins leads to shunting around the obstruction into collateral veins involving the skin of the abdomen (caput medusae), esophagus (varices), pelvis (hemorrhoids), and spleen (splenomegaly). There may be areas of hepatic necrosis if severe or prolonged venous obstruction occurs. Causes of Budd-Chiari syndrome can include myeloproliferative disorders (particularly polycythemia vera), coagulopathies, paroxysmal nocturnal hemoglobinuria, hepatocellular carcinomas, and intra-abdominal carcinomas. Some cases are idiopathic. In this case, a coagulopathy due to Trousseau syndrome from the underlying breast carcinoma is the likely cause.5,6

Banti syndrome is subclinical extra-hepatic portal vein obstruction leading to esophageal varices and ascites. Caroli disease is a form of altered biliary tract architecture with portal tract fibrosis, often congenital, leading to segmental dilation of larger ducts. Peliosis hepatis refers to hepatic sinusoidal dilation forming blood lakes, and most cases are related to steroid use. Hepatic veno-occlusive disease refers to obstruction of small hepatic vein branches from toxic injury to sinusoidal endothelium, usually associated with chemotherapy given along with bone marrow transplantation or with ingested alkaloids (Jamaican bush tea).5

4. Which of the following is the most likely immediate cause of death? Respondents
No. %
Pulmonary thromboembolism 147 98.7
Metastases 2 1.3
Ascites - -
Opiate overdose - -
Sepsis - -

The chest CT scan prior to death [AU-01 (J)] documents an area of decreased attenuation (i.e., darker) in the pulmonary arterial trunk, and a pulmonary thromboembolus was confirmed at autopsy. The patient had at least two documented episodes of chest pain with dyspnea consistent with recurrent thromboembolism, and the pelvic vein thrombus found at autopsy suggests the source for the thromboemboli. The coagulopathy associated with cancers, Trousseau syndrome, often results in phlebothrombosis with risk for thromboembolism. The risk for venous thromboembolism associated with malignancy increases with chemotherapy, surgery, and placement of central venous catheters.  Hormonal therapy, such as tamoxifen given for treatment of breast cancer, may also increase the risk.7

The ascites she had was not of sufficient size to compromise pulmonary function. Though she had metastases which likely resulted in pain, she did not have a sudden event from them leading to death. The opiates given in hospice for pain management may have been given at high doses, but do not produce sudden dyspnea, and are more likely to cause respiratory depression. In general, too little pain medication is given for cancer patients, not too much. In one study, persons treated with high doses of morphine survived longer than those treated with low doses or not at all.8 Though pneumonia with sepsis is common in bedridden patients, there is no evidence for it in this case.

5. Analysis for mutations in which of the following genes would likely be of greatest value for the female relatives of this patient? Respondents
No. %
BRCA-1 147 98.7
BCL-2 1 0.7
K-RAS 1 0.7
N-MYC - -
p53 - -

The patient’s young age suggests that there is a greater likelihood for a hereditary basis for her breast cancer. Though only about 3% of all breast cancers are associated with BRCA-1 and BRCA-2 mutations, about 25% of familial breast cancers have these mutations. The median age at diagnosis is about 20 years earlier than for women with sporadic breast cancers. The other listed genes are associated with a variety of malignancies. Of those listed, BRCA-1 and p53 are most likely to be seen with sporadic breast cancers.1

Genetic testing of her 11-year-old daughter is not recommended at this time according to recommendations of the American Academy of Pediatrics and others. If the BRCA-1 gene were present, there would be no additional therapeutic intervention prior to her legal adulthood. At that time, the child would be free to choose whether or not to undergo genetic testing. Even adults can find it difficult to understand the meaning of such information that gives long-term probabilities, but no short-term certainties.9,10

The genetic testing and participation of children in research protocols is an active area of bioethical debate involving informed consent of parents, mandated neonatal screening issues and the need and capabilities of child “assent” to studies and testing. Assent is a fairly recent addition to the pediatric ethics requirements, and involves full disclosure of risks and benefits to the child and the child’s agreement to participate, and then getting the parents’ consent as well. It is usually thought to be appropriate starting as young as age 7, though with language modified appropriately to the level of comprehension of the child. For teenagers, assent is clearly ethically mandatory. Guidelines regarding genetic carrier testing of minors generally include the following: (1) carrier testing should not be performed in children, and (2) testing should be deferred until the child can give proper informed consent to be tested. Carrier status is really only relevant for decisions concerning marriage and childbearing, and so such decisions are usually safely deferred until age 18.9,10

Debate remains regarding issues concerning communication of incidentally discovered carrier status, follow-up to insure that children are properly informed about genetic risks when they are older, and when exceptions should be made to rules withholding or deferring genetic testing of minors. Here the issue often hinges on balancing potentially harmful information with little immediate medical value against keeping secrets. That is, someone already knows the information and sometimes the only thing worse than finding out bad news is finding out that someone you knew and trusted kept bad news from you.11

6. Which of the following complications affected her ability to perform activities of daily living just prior to death? Respondents
No. %
Depressive disorder 147 98.7
Anxiety disorder 1 0.7
Psychotic disorder 1 0.7
Personality disorder - -

The history following her diagnosis of breast cancer suggests depression. Lowered mood, difficulty in thinking, loss of interest, loss of energy, and excessive sleep can be features suggesting depression. Feelings of sadness and general emotional distress are a common reaction to a diagnosis of cancer. Patients with a greater amount of social support available tend to cope better. About a fourth of breast cancer patients are diagnosed with a clinical depression, similar to the overall average incidence for depression in patients with all forms of cancer. Of the patients that do develop a clinical depression, there is direct overlap of some symptoms of depression and cancer treatments (e.g., fatigue, general somatic complaints such as appetite and sleep disturbance). Pain management techniques and behavioral techniques targeting nausea and coping strategies for painful procedures are also effective. For patients with more severe levels of depression, antidepressant medication may be used.12

Anxiety disorders are the most common form of mental disturbance in the United States. Anxiety occurs in association with many physical illnesses, drug therapies, and psychiatric disorders. Anxiety is defined by the presence of unpleasant and unwarranted feelings of apprehension sometimes accompanied by physiologic symptoms. There are many forms of anxiety disorder, but the most common is generalized anxiety disorder characterized by excessive anxiety and worry on most days, for at least 6 months, about a number of issues, and difficulty controlling the worry. Personality disorders are coping styles that are inflexible and maladaptive; they are chronic and lifelong. Psychosis associated with malignancy may result from marked hypercalcemia as a paraneoplastic effect from elaboration of parathormone-related peptide by the neoplastic cells.13

7. Which of the following is the most appropriate role of hospice care for patients such as this? Respondents
No. %
Pain management 147 98.0
Decrease medical costs 2 1.3
Treatment of psychiatric disorders 1 0.7
Chemotherapy - -

For adult patients with cancer, the concept of end-of-life care, including hospice care, is well accepted. Some may think hospice is a place, but it is a treatment philosophy. It may mean going to a hospice facility (and those are often very nice places), but more than half of hospice patients now stay at home and receive hospice care delivered in their home by visiting nurses and an occasional house call by the medical director. What distinguishes hospice care is usually the inclusion of things like pastoral counseling, art and music therapy, and aggressive pain control for improvement in the quality of life, especially the generous use of opioids when called for and the correct management of their side-efects.14,15

The average stay in hospice is two weeks, and in many communities even less time than that. Yet the insurance coverage for hospice care may extend for up to 6 months. The tragedy is so many patients don't want to admit they are dying until the very end, and many doctors don't want to give a prognosis of less than 6 months and be wrong, and so tend to wait too long as well. Thus, many patients never fully take advantage of the benefits of hospice. When should the patient be referred to hospice? Soon after a bad diagnosis, the patient may still be reassured that there is some hope of remission, and that even if there is no remission there is still hope for some meaningful life to be lived for a period of time. Explain that hospice will help them with the latter goal. Keep preparing the patient so that when the day comes, it isn’t taken as the worst news they ever got, but just a part of a well-planned, and even rehearsed, series of events in the progression of the disease. The goal should be to give the patient as much time in hospice as possible, not to predict the time of death as accurately as possible. The latter is what causes all those two-week stays. If the disease largely limits the patient to life at home, and no longer going out, it is definitely time for hospice. If the disease limits them to bed, then it is long past time. (There are more exact guidelines available from

8. Who should explain the autopsy findings to the decedent’s mother? Respondents
No. %
Pathologist 92 61.3
Oncologist 51 34.0
Genetic counselor 7 4.7
Hospital administrator - -
Nurse - -
Pastoral care provider - -

The member of the health care team best suited to explain autopsy findings is the pathologist. Though autopsy reports may be sent to physicians who cared for the patient in life, and the pathologist may talk to those physicians regarding the autopsy findings, clinicians did not perform the autopsy and may not be able to relate the findings clearly, or may misinterpret the findings. The pathologist can carry the discussion of the findings as far as (s)he feels comfortable and competent.17 More specific interpretations that relate to treatment or to potential consequences for family members may need to be delivered by clinicians or health care workers such as clinical geneticists who have more specific knowledge in a particular field of medicine. At times, a joint conference with the pathologists, family, and other members of the health care team may be appropriate. As a professional courtesy, the pathologist should probably not discuss the case with the family without the knowledge of the treating clinician.

The autopsy consent in this case had restrictions. An autopsy consent form must include language that makes it clear to those signing the form that limitations may be placed upon the procedure. The consent form must make it clear that organs and tissues may be retained, and give the person granting consent the option of limiting any retention of tissues. Any restrictions must be clearly documented and communicated so that the pathologist performing the autopsy understands the restrictions. The autopsy consent in this case was obtained from the next-of-kin, which is defined by statute. The order of obtaining consent for autopsy from relatives is typically established by statute for each state.  A common order of next-of-kin for obtaining consent is as follows:

  • surviving spouse
  • child, if 18 years or older, otherwise the legal guardian of the child
  • parent
  • sibling
  • uncle or aunt
  • nephew or niece
  • cousin
  • others charged by law with the duty of burial

Variations for next-of-kin status, medical power of attorney (which may cease at death), rights of partnered couples or “common law” spouses, and rights of same-sex couples depend upon state and local statutes and their interpretation.

For CAP laboratory accreditation, consenting procedures must be defined precisely and must conform to state and local statutes (ANP.31070).

Key Teaching Points:

  • Less than 1% of breast cancers have metaplastic components that can include epithelial and/or mesenchymal components.
    • Epithelial components include ductal, squamoid, medullary, mucinous, or apocrine patterns.
    • Mesenchymal components may show fibrosarcomatous, cartilaginous, muscular, osseous, or vascular differentiation, but sometimes consist solely of poorly differentiated spindle cells.
  • Trousseau syndrome with hypercoagulable state may lead to pulmonary thromboembolism and, less commonly, hepatic venous outflow obstruction consistent with Budd-Chiari syndrome.
  • Though only about 3% of all breast cancers are associated with BRCA-1 and/or BRCA-2 mutations, about 25% of familial breast cancers have these mutations, and a younger age at onset of breast cancer increases this likelihood.
  • About one fourth of all cancer patients, including those with breast cancer, are diagnosed with clinical depression.
  • End-of-life hospice care can be useful for pain management in cancer patients.


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Edward C. Klatt, MD
Autopsy Committee

Elena Reyes PhD
Jeffrey Spike PhD