Breast Mass

Roy O’Neil
Pathlet 2012

These pathlets are edutainment. This site collects no information about visitors, and cannot substitute for your own doctor's care. There are many questions without clear right-or-wrong answers.


Mother With Her Children
Hippolyte Paul Delaroche
August 2012, Denver. Late one snowy day in Denver, a 57-year-old Caucasian, vagabond woman, Ms. Jane Nomad, presents to your emergency department with a firm, painless mass in her left breast. Due to the down turn in the economy, health insurance has not been a top priority. She has not seen a physician in 6 years.  She reports that she has been feeling fine, but her new boyfriend insisted that she seek medical attention because he cares.

Social history: Ms. Nomad smoked two packs of cigarette a week, for the last thirty years. Drinks alcohol, a six-pack every couple of days and used a variety of illicit drugs since leaving home 40 years ago.  She has had five, successful vaginally delivered, pregnancies, consisting of three boys and two girls, all with different fathers. She believes her left breast has not stopped lactating since her last pregnancy at age 41. She recalls no family or surgical history.

Physical exam reveals an obese 5’2” woman weighing 165 lbs. She is alert and oriented times three. Oral temperature is 98.2 F, pulse 88, respirations 20. Her breath and heart sounds are normal. Visual inspection of the left breast: reveals some asymmetry as compared to the right, the skin shows no erythema or ulceration. The patient’s left nipple is inverted slightly medial when compared to her right.   You palpate a ill-defined mass in the left breast, upper outer quadrant that is approximately two centimeters, in diameter and moderately tender to your touch. Her left bra cup appears lightly stained with blood.

What do you do next?

Labs:

      CBC

      Chem. panel

      Drug screen

      Blood cultures

      Coagulation studies, including protein C and S

Radiology

      CAT scan

      Mammogram left breast

      MRI whole body

      Chest x-ray

Specialist consults:

      Dr. Glowing personality, the local radiologist

      Dr. Sharp Knife, the local surgeon

      Dr. Path-Guy, the local expert pathologist

      Dr. Gotta Bug, the local infectious disease specialist

      Dr. Up’s Downs, the local endocrinologist

      Dr. Ready Catch, the local OB-GYN

      Dr. Onc Drugs, the local oncologist

The radiologist ("Dr. Glowing Personality") issues the following report:

Mammogram left Breast: Ill-defined spiculated density, irregular borders, with spiculated irregular microcalcifications, and two additional similar, but, smaller clusters of microcalcification surrounding the main lesion.

Dr. Knife also received this report, evaluated the patient, performed the biopsy and sendy the specimen to pathology.

Dr. Path-Guy, receives multiple 0.2 X 0.2 X 2.8 cm cores of gray white to tan tissue. The specimen is submitted entirely for processing. The next day the H&E slides come out, you (her physician from that fine medical school KCUMB) are sitting with Dr. Path-Guy and see the flowing pictures. Dr. Path-Guy points out, in a few areas of the slide (not shown in the composite photograph) foci of DCIS with comedo necrosis and microcalcification.

Here's a composite photo. Make the call.
      Inflammatory carcinoma of the breast

      Lobular carcinoma of the breast

      Invasive carcinoma of the breast

      Metastatic malignant melanoma

      Atypical ductal hyperplasia

      Ductal carcinoma in situ

      Lobular hyperplasia

      Atypical lobular hyperplasia

      Paget’s disease

      Intraductal papilloma

      Atypical intraductal papilloma

We hope this was easy. Instead of a single layer of ductal cells, the ducts contain a mass of anaplastic cells with large nuclei and scanty cytoplasm. There's no suggestion of the double cell population of atypical hyperplasia. You can make the call of ductal carcinoma with confidence. Dr. Path-Guy says, “now that you have made an accurate diagnosis of Ductal carcinoma in-situ, according to CAP how would you grade it”? A table and definitions from the Collage of American Pathologist cancer checklist is provided for you below.

The architectural pattern has been reported traditionally for DCIS.  However, nuclear grade and the presence of necrosis are more predictive of clinical outcome.

The nuclear grade of DCIS is determined using 6 morphologic features (Table 2).4,30


Feature

Grade I
(Low)

Grade II (Intermediate)

Grade III
(High)

Pleomorphism

Monotonous (monomorphic)

Intermediate

Markedly pleomorphic

Size

1.5X to 2X the size of a normal RBC or a normal duct epithelial cell nucleus

Intermediate

>2X the size of a normal RBC or a normal duct epithelial cell nucleus

Chromatin

Usually diffuse, finely dispersed chromatin

Intermediate

Usually vesicular with irregular chromatin distribution

Nucleoli

Only occasional

Prominent, often multiple

Mitoses

Only occasional

Intermediate

May be frequent

Orientation

Polarized toward luminal spaces

Intermediate

Usually not polarized toward the luminal space

An RBC or small lymphocyte can be used microscopically to gauge the size of a neoplastic or normal cell.

The presence of necrosis is correlated with the finding of mammographic calcifications (i.e., most areas of necrosis will calcify).  DCIS that presents as mammographic calcifications often recurs as calcifications.  Necrosis can be classified as follows:

Necrosis, should be carefully distinguished from secretory material, which can also be associated with calcifications, cytoplasmic blebs, and histiocytes, but does not include nuclear debris. 

What shall we call this?

Again, we hope this wasn't difficult. To further characterize the DCIS, and provide prognostic information to Dr. Drugs, (the local oncologist) what immunohistochemical stains would you order?

Let's order up some special stains for this lady so that Dr. Drugs, the oncologist, can have prognostic information. You choose.

p63
   (myoepithelial nuclei)
     
phospho-p53
   (experimental)
     
HER2/neu
   (guide Rx)
     
HMB45
   (melanoma)
     
CK 5/6
   (myoepithelium)
     
Progesterone receptor
   (glia)
     
CD10
   (some leukemias)
     
Estrogen receptor
   (glia)
     
cd138
   (lymphoma / myeloma)
     
c-kit
   (lymphoma / GI stromal / seminoma)
     
Smooth muscle actin
   (myoepithelium)
     
Calponin
   (breast myoepithelium)
     
CD99
   (Ewing's, more)
     

Final diagnosis: Ductal carcinoma in-situ, high-grade with focal comedo type necrosis, solid and cribriform sub-type, and intermediate grade nuclei.

 

Positive for estrogen and progesterone, negative for HER2/neu

What special genetic testing might you do so Ms. Nomad can inform her two daughters about risks they may face?

You contact Dr. Knife, the local surgeon ( who performed the biopsy. He sets her up for a mastectomy. Dr. Drugs (the local oncologist) agrees to follow up with her after the surgery. Ms. Nomad is ever grateful to her boyfriend for insisting she seek medical attention.

Discussion:

Carcinoma of the breast is responsible for over 40,000 deaths annually among women, second only to lung cancer. This woman presents with nipple discharge that appears bloody as indicated in this case by her blood stained bra. The risk of malignancy with discharge increases with age. The average age of diagnosis for Caucasian women is 61 and increases with several risk factors including but not limited to: obesity for postmenopausal women (due to synthesis of estrogen in fat deposits), long duration of breast feeding and affected first-degree relatives. A woman with a mutation in the BRCA1 gene has a 40%-90% of developing breast cancer by age 70.

Detecting breast cancer early is key to a good prognosis. Women should check themselves regularly with self-breast exams. Physicians should remind patients and teach them the appropriate way to perform self-breast exams if necessary and /or provide literature to their patients. The daughter of the woman in this case could undergo genetic testing and take further steps to lessen her risk of developing breast cancer later in life. Among many options, Prophylactic mastectomy provides the highest reduction is breast cancer risk (89.5-100%). This brings up an interesting discussion; with the advancement of cancer detection, how far is one willing to go for prevention?


Roy O'Neil, KCUMB '15

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