Julio Ibarra is a pathologist par excellence. He is passionate about the education of breast cancer issues for all women. He is a key member of the Breastlink multidisciplinary team, bringing great depth and insight to the field of pathology.

Understanding the information included in your pathology report is critical for your understanding of the disease process and treatment decisions. The pathology report includes a number of details that are used by the oncologist, the surgeon and the radiation therapist to make decisions regarding treatment.

In this article I will dissect a pathology report and provide you with definitions of the different terms used in pathology, so that you have the tools necessary to be an integral part of the decision-making team.

Demographics

This establishes the identity of the biopsy by providing the patient's name, date of birth/age, sex, and usually the name of the doctor who ordered the study, usually a surgeon. It also includes the date of the biopsy/surgery. All this information allows you to confirm that the report belongs to you and corresponds to the tissue that was obtained from your body.

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Clinical Information

This is the information that the surgeon or the oncologist has provided to the pathologist when the biopsy/excision is submitted to the laboretory. It is important to the pathologist for several reasons. First, it indicates whether there is history of another biopsy from the same breast. If this is the case, the pathologist will usually want to review the old material and compare it to the new ones. This may help in trying to distinguish a recurrence from a brand-new tumor. It also helps the pathologist know if we are searching for a large or small tumor, for a slow-growing or fast-growing tumor, etc.

Specimen submitted. In this section, the surgeon indicates the tissue that is being submitted for evaluation by the pathologist. For safe record keeping and to increase the integrity of every specimen submitted, we prefer to have each specimen in a different container with a different label indicating what the specimen represents. A core biopsy, for example, will have one part per tumor sampled, even if multiple biopsy fragments were obtained from the same tumor. On the other hand, in surgical cases we often receive multiple parts. For example, a patient who has a sentinel lymph node biopsy, a partial mastectomy (segmentectomy, quadrantectomy, etc) and additional margins may have multiple parts to the case. The list would look something like this:

A) Sentinel lymph node #1
B) Sentinel lymph node #2
C) Partial mastectomy
D) Additional medial margin
E) Additional superior margin
F) Additional posterior margin

If all these specimens were sent to the laboratory in one large container, the probabilities of missing some of the small parts would increase. We prefer to keep them separately identified. This also allows for a clear diagnosis list, indicating the specifics of each part. For example, if the main specimen indicates that there is tumor at the medial margin but the additional medial margin indicates that the new margin is now free of tumor, the surgeon knows that the entire tumor has now been removed. This will also be summarized in the synoptic report or template.

Description of procedure. This is a section that not every laboratory includes. We use it only for needle biopsy, core or fine needle (FNA) cases. We use it because it helps us include in the body of the report the information provided by the radiologist regarding the specific lesion being biopsied. The radiologist usually provides mammography and ultrasound information regarding the samples being submitted. For example, the radiologist may say that the lesion or tumor being biopsied is round, smooth and solid and measure 1.0 cm in diameter. The radiologist will also indicate that he or she obtained four core biopsies from that tumor. When we review the material submitted, we match the number of biopsies obtained with the number we see in the container. This is another checkpoint to indicate that we have, in fact, received everything that the radiologist sent. When we review the tumor sections the following day, we match the radiologic information with the pathologic findings. For example, in the case of a round, smooth, solid lesion, we will expect to see a tumor made out of cells and supporting tissue (stroma) and not a cyst (a cavity with fluid); we also expect to see a lesion that is well defined and easily outlined from the surrounding "normal" breast tissue. In other words, we are looking for something similar to a grape in a bowl of jelly.

Gross Description

This is also known as macroscopic description and it is the description of what the pathologist sees, feels and smells when he or she receives the sample in the laboratory. It includes the measurement of the tissue removed and the measurement of the tumor inside of the tissue. It often includes also the orientation of the margins by different colors of ink. The tumor will be described as it relates to consistency, color and proximity to the edges of the tissue removed. For duct carcinoma in situ, the determination of tumor or margins will be done at the microscopic level since the majority are non-palpable and non-visible.

Microscopic Description

This section describes the pattern of the tumor. We can determine if the tumor is benign or malignant, and if malignant, whether it is non-invasive (in situ) or invasive (infiltrating). We can determine whether the tumor is of ductal or lobular type, as well as the histologic grade of the tumor which indicates the level of aggressiveness of the cells. The features indicated in the microscopic description will be summarized in the diagnosis.

Diagnosis

The diagnosis can be a line diagnosis or a summary or synoptic diagnosis. We prefer to use the synoptic template because it helps to make sure that we include every important piece of information that the oncologist, surgeon or radiation therapist will need for treatment decisions.

Anatomic site:		Breast, side, Quadrant, o'clock, etc.
Size of specimen:		___ X ___ X ___ cm. (In centimeters)
Size of tumor:		___ X ___ X ___ cm.
Histologic type:		Invasive ________ carcinoma,
Histologic grade:		Specific grade (__/9 MBR Scale of 3-9/9)
		__/3 -Tubules
		__/3 -Nuclear grade
		__/3 -Mitosis
Necrosis (Other than CIS):		Present or not present
In situ carcinoma:		Present or not, uni or multifocal.
	Type of CIS:	Histologic type and pattern of growth.
	Nuclear grade:	Low, intermediate or high.
	Necrosis:	Present or not.
	Percentage:	___%
	EIC:	Present or not
Margins of resection:		Negative or positive (invasive or in situ)
	Closest margin:	__ mm from margin (in millimeters)
Lymphatic invasion:		Present or absent.
Skin involvement:		N/A or Present/absent
Nipple involvement:		N/A or present/absent
Microcalcification:		Present or absent and where (i.e.: in DCIS)
Background:		Proliferative breast disease, atypical ductal hyperplasia, atypical lobular hyperplasia, etc.
Prognostic markers:		See addendum report.
Lymph nodes:		Positive or negative and count (___/___)
TNM classification:		T__, N__, M__ (See explanation last page).

Our synoptic template for duct carcinoma in situ (Non invasive) is the following:

anatomic site:		Breast, side, Quadrant, o'clock, etc.
(Ca++, mass, distortion)		For _______________ (reason, if known)
size of specimen:		__ X __ X __ cm. (In centimeters)
histologic type:		Ductal carcinoma in situ
Type of CIS:		Histologic type and pattern of growth.
	Nuclear grade/CIS:	Low, intermediate or high nuclear grade
	Necrosis:	Yes or no
size of lesion:		In centimeters (see below)*
microcalcifications:		Present or not and where (i.e.: in DCIS)
margins of resection:		Positive or negative
	Distance to edge:	<1mm, 1-9mm, >9mm
lymph nodes:		None available, or __ benign lymph nodes (__/__)
TNM classification:		Tis, N__, M__ (see last page).

Diagnosis and Comment

The anatomic location, surgical procedure and reason for surgery are self-explanatory and serve the purpose of confirming that the tissue received was, in fact, the correct one.

The size of the tumor is extremely important and one of the most difficult items. When tumors are palpable and visible by the pathologist, a size will be recorded in the gross description, and often that is the size recorded in the report. When the tumors are small, however, particularly under 10 mm in size, it is difficult to make sure of their size grossly because they may be surrounded by fibrosis (scar-type tissue) and would give the impression that they are bigger than they really are. In these instances it is important to measure the tumor under the microscope and confirm the size. Size of tumor is an extremely important prognostic indicator. In Dr Tabar's series in Sweden, he has found that patients with tumors that measure 10 mm or less have a survival rate of over 94% at 20 years after surgery. In his series, the size is prognostic irrespective of the histologic grade of the tumor.

The histologic type refers to the pattern of growth of the invasive carcinoma. Even though there are many names for different types of invasive (infiltrating) carcinomas, there are two main types:

Ductal (85% of breast cancers) (See image 2)
Lobular (15% of breast cancers) (See image 3).

Ductal carcinomas grow in a pattern where the tumor cells make an attempt to replicate the tubules normally found in the breast. Lobular carcinomas of the classic type (the most common of the lobular types) grow with tumor cells aligning themselves in a single file pattern, and the surrounding tissue has increased fibrous stroma or collagen. Infiltrating lobular carcinomas have a tendency for multifocality. That is, they grow forming many simultaneous tumor nodules that tend to fuse into each as they grow. Both of these tumors need to be graded and usually the prognosis is linked to the grade and not so much to the histologic type of growth.

Histologic grade refers to the aggressiveness of the tumor cells as we see them under the microscope. We have three grades: low, intermediate and high (well differentiated, moderately differentiated and poorly differentiated). The system we use to grade was created many years ago and has been modified several times. The last modification was done in England. This is commonly known as Modified Scarff-Bloom Richardson (MBR). Other grading systems include Black' nuclear grading and the Nottingham prognostic index. The MBR uses three histologic features: formation of tubules, size and staining quality of the nucleus and finally the number of dividing cells (mitosis) at the of the tumor. Each one of these parameters has 1-3 points; one point for the low grade or well differentiated, 2 points for the middle or intermediate grade, and 3 points for the high grade or poorly differentiated tumors. After assigning points to each parameter, these are added up. The total score is then interpreted as follows: 3-5 points: low grade or well differentiated; 6-7 points intermediate grade; and 8-9 points high grade or poorly differentiated. Prognosis has been associated to histologic grade of tumors. Patients with low grade tumors tend to have a lesser rate of local or systemic recurrence than those with higher grade tumors. (See images 4 through 7).

The presence of duct carcinoma in situ (DCIS) within the invasive carcinoma has some significance for local recurrence. Those patients with large amounts of DCIS within and around the invasive component have traditionally shown a higher rate of local recurrence. This is believed to be due to incomplete excision of the non-invasive tumor part. DCIS can be difficult to extract due to the nature of this condition. It grows along the milk ducts which resemble the branches of a tree and therefore can grow in different directions and branch out, making it difficult for the pathologist to determine margin status. With DCIS we prefer to have a margin of 10 mm minimum before we start to feel secure that the entire DCIS lesion has been removed. This information is based on scientific studies that have determined the rate of local recurrence for DCIS when the margins vary from 1 mm or less to 10 mm or more. (See imeges 8 through 11).

Margins of resection for invasive carcinoma, of course, have prognostic significance. A patient who has a tumor at the margin is at a higher risk of recurrence because the tumor has not been entirely removed. In reality this would represent regrowth rather than recurrence. With invasive carcinoma, we require that the margin has no tumor transected but not need the 10 mm we require for DCIS. Decision for radiation therapy and use of different modalities of this type of therapy will be based in part on the status of the margin of resection.

Lymphatic or lymphovascular invasion refers to the presence of nests of tumor cells from invasive carcinoma within lymphatic or vascular spaces. Lymphatic are those vessels in the body which drain the lymph fluid from the intercellular space and lead to lymph nodes. The implication of observing lymphatic invasion is that those tumor cells are on their way to a lymph node. There is scientific evidence that demonstrates the fact that patients with lymphatic/lymphovascular invasion (LVI) have a higher incidence of recurrence of the breast cancer, even if the regional lymph nodes do not demonstrate metastasis at the time of the pathologic examination. (See image 12).

Skin involvement can be seen in two forms. Direct invasion of the skin by tumor cells may indicate that the tumor may create an area of breakdown of the skin (ulceration). This creates a perfect medium for bacteria to grow and help deteriorate the condition of the skin locally. The second form involves the lymphatic vessels in the dermis (the soft tissue immediately under the skin surface). This phenomenon is often associated with skin redness and a warm feeling of the surface which resembles an infectious or inflammatory process, and therefore this condition is known clinically as inflammatory carcinoma. Dermal lymphatic invasion is a prognostic indicator for systemic disease. It is a condition that can be treated surgically but often needs systemic treatment (chemotherapy).

Nipple involvement refers to the presence of tumor within the nipple. This can be in the form of an extension of the non-invasive form (DCIS) into the milk ducts that reaches the nipple. This is seen in a small percentage of patients with DCIS. Involvement can also be by invasive carcinoma and the significance is essentially the same as with invasion of the skin in other areas of the breast.

The presence of microcalcifications (concretions made of minerals that are seen mammographically and most frequently contain salts) is not necessarily a prognostic marker but more a helpful indicator for the radiologist. DCIS, for example, often presents itself as a nonpalpable lesion and is found by mammography due to the presence of "microcalcifications". When these lesions need to be removed, the radiologist works in concert with the surgeon to bracket the entire area of calcification with metal wires. Once the wires are placed, the surgeon knows how much and from where to remove breast tissue. The surgeon is working "blindly" in these cases and is guided by the radiologist. The pathologist then observes the calcium in the sections and compares it with the calcifications in the mammograms, and determines whether the calcifications are the same. This is not always simple to do, and often requires the radiologist and the pathologist to work together. DCIS is not always calcified. The pathologist will determine and mention in the report is the DCIS is calcified and to what extent. Calcifications can also occur in the stroma (soft tissue surrounding invasive tumor cells). These have no prognostic significance but also require correlation with the mammograms.

Background refers to the breast tissue that is not tumor. The presence of risk markers (atypical lobular hyperplasia-ALH, lobular carcinoma in situ-LCIS, lobular neoplasia-LN, radial scars, micropapillomas or other proliferative lesions) will be mentioned by the pathologist in the report. Of course, the presence of a risk marker in a patient who already has an invasive carcinoma has no additional value. The identification of these risk markers has tremendous implications for treatment when they are the sole finding in a biopsy. For example, the finding of lobular neoplasia indicates that the patient has an increased risk for the development of an invasive carcinoma in either breast over her lifetime. A discussion of risk can be found in other areas of this site.

Prognostic markers refers to the secondary markers we perform on breast cancers. The most frequently utilized by most oncologists are estrogen and progesterone receptors and Her2neu oncogene. Estrogen and progesterone determine if the tumor cells have receptors on their surface for the hormones estrogen and progesterone. If they do, these tumor cells respond to treatment with drugs such as Tamoxifen, Raloxifen, etc. (See image 13).

Her2neu is an oncoprotein which belongs to the family of the growth hormone receptors. The overexpression of the protein can be identified by observing heavy staining against this protein on the membrane surface of the tumor cells by immunohistochemistry. Also, the amplification of the gene can be determined by examining the gene by fluorescent techniques. When the gene is amplified, more than the usual number of copies of the gene will be observed under fluorescent microscopy. Usually there is good correlation between amplification of the gene and overexpression of the protein. Patients with overexpression/amplification of this oncoprotein respond well to treatment with Trastuzumab (Herceptin) therapy. This is discussed in more detail in the oncology treatment section.

Lymph nodes are the single most important prognostic factor known in breast cancer to predict systemic recurrence. Patients with positive lymph nodes unfortunately have a higher incidence of recurrence of disease. The number of nodes is also prognostic in that, as the number of positive nodes increases, the probability of recurrence also increases. In the past, surgeons obtained lymph nodes from the low and high axilla (levels one and two) and sometimes from the supraclavicular location. The number of nodes varied from patient to patient from anywhere between around 10 to 30.

A few years ago, the technique of sentinel lymph node biopsy was introduced. By this technique, the surgeon obtains the lymph node(s) that are most likely to harbor metastases. These are the first draining lymph nodes which are identified by either injecting a dye into the breast (around the tumor or around the areola) and then looking in the axillary basin, or by injecting a radioactive material which will end up in the lymph nodes. The surgeon will identify them with a radioactive material counter. Sentinel lymph nodes are processed differently by the pathologist. These nodes are sections serially every 2 mm and entirely submitted for microscopic examination (SLN diagram). Sometimes we do a scrape and smear or a touch imprint of the node at the time of the operation to see if we identify metastases. If we do, the surgeon will remove additional lymph nodes from the axilla. (See image 14).

Finally, the synoptic report includes the TNM classification. This is based on the American Joint Committe on Cancer (AJCC) guidelines and includes the clinical and pathologic information that allows your doctors to stage the disease process within your body. The "T" indicates the tumor size, the "N" indicates the status of the lymph nodes and the "M" indicates the presence or absence of distant metastasis.

TNM simplified breakdown:
Tis: Ductal carcinoma in situ (DCIS)
Tmic: Invasive tumor smaller than 0.1 cm
T1a: Invasive tumor 0.1 to 0.5 cm in size
T1b: Invasive tumor 0.6 - 1.0 cm
T1c: Invasive tumor 1.1 - 2.0 cm
T2: Invasive tumor over 2 cm but not larger than 5 cm
T3: Invasive tumor larger than 5.0 cm
T4: Invasive tumor of any size with extension to chest wall, skin, inflammatory carcinoma

NX: Unknown lymph node status
N0: Negative lymph nodes
N1: 1 - 3 positive axillary lymph nodes
N2: 4 - 9 positive axillary lymph nodes
N3: 10 or more positive lymph nodes

MX: Unknown metastatic status
M0: No distant metastasis
M1: Distant metastasis

For duct carcinoma in situ (DCIS) the synoptic summary includes similar findings to those described for the invasive carcinoma synoptic template. Two items need special discussion: the type of DCIS including nuclear grade and the size of the tumor.

DCIS can have different architectural types of growth. These include solid, comedocarcinoma, cribriform, micropapillary and encysted papillary. The pattern of growth does not provide prognostic significance. The nuclear grade of the DCIS does provide prognostic significance. The grades include low, intermediate and high nuclear grades. Low grade nuclei represent nuclei which have the size of no more than 1.5 times the size of a normal red blood cell. High grade nuclei are those that are 2.5 times or larger than a normal red blood cell. Low nuclear grade and high nuclear grade DCIS can grow in any of the patterns described above. In addition to the nuclear grade, there are two additional items involved in the prognosis of DCIS. These are the size of the tumor and the presence or absence of necrosis. There is abundant literature that indicates that the higher the grade, the presence of necrosis and the proximity to the margin of resection are strong prognostic indicators for local recurrence. These literature reviews have been criticized by some observers because they were not obtained from randomized trials. We should keep in mind, however, that all this information was obtained prospectively from archival material and is considered valid information.

The size of DCIS is difficult to assess. We use the sequential sectioning technique by which we serially cut the breast excision at similar thickness intervals and then submit for microscopic review either the entire biopsy or selected sections in sequential order. This allows us to count the number of slices that have DCIS by examining the microscopic slides. For example, a biopsy that measures 10 cm in greatest dimension is sectioned at 0.5 cm intervals. We end up with 20 slices of tissue. We find out that five of the slices contain DCIS when we examine them under the microscope (remember DCIS is almost always not visible without a microscope and not palpable). We conclude that the size of the DCIS is 2.5 cm because five slices at 0.5 cm each = 2.5 cm.

Every woman who finds herself involved in making treatment decisions about her cancer care needs to ensure that she feels confident about her pathology report. This can be seen as important as the "engineers report" off which significant decisions are made.

For further information, or to have your pathology report reviewed in a second opinion, contact Breastlink.

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Demographics Clinical Information Gross Description Microscopic Description Diagnosis Diagnosis and Comment