Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (260 page)

Cancer of the breast is a malignancy arising from the breast epithelium (carcinoma) and/or stroma (sarcoma).

Clinical Presentation

Breast cancer is the most common malignancy in women and a leading cause of cancer death. Risk factors include increased age and female gender, race, preexisting benign breast disease, family history of breast or ovarian cancer, exposure to ionizing radiation, and environmental factors.

   Laboratory Findings

The diagnosis of breast cancer is made on mammographic and/or ultrasound findings followed by biopsy and histologic evaluation. Patients with a familial history of breast cancer may be screened for BRCA1 and BRCA2; however, <10% of all breast cancers are associated with genetic mutations (see Chapter
10
).

The histologic types of breast carcinoma include infiltrating ductal carcinoma (see eBook Figure 8-1C), infiltrating lobular (see eBook Figure 8-2D) carcinoma, and mixed ductal/lobular carcinoma. In addition, there are sarcomas and mixed tumors, phyllodes tumor (see eBook Figure 8-3C).

Molecular subtypes include luminal subtypes A and B (the majority of ER-positive breast cancers), and HER2-enriched (often negative for ER and PR), basal subtypes (triple negative) (see eBook Figures 8-1 to 8-3).

At the time of diagnosis, immunohistochemical staining is performed on the tumor to determine estrogen (ER) and progesterone (PR) receptor expression for prognosis and human epidermal growth factor 2 (HER2) receptors to determine if the patient will respond to Herceptin. Grading is based on architecture, nuclear morphology, and the number of mitoses using a system such as the Scarff-Bloom-Richardson grading system. Staging is based on the TNM system from the American Joint Committee on Cancer and the International Union for Cancer Control.

CANCER OF THE CERVIX

   Definition

Squamous cell carcinoma of the cervix is one of the most frequent neoplasms that affect a woman’s reproductive system
¹
(see eBook Figure 8-4A). Cervical squamous cell carcinoma is the result of infection with various strains of the human papilloma virus (HPV), especially (but not exclusively) the oncogenic types 16 and 18. Persistent viral infection transforms the epithelial cells that undergo a progression of changes in the cervix particularly at the squamocolumnar junction, which can be identified on Pap testing and on biopsy. The progression from acute infection to dysplasia to invasive carcinoma may take 3–7 years. Regular screening for high-risk HPV and by Pap testing has decreased the incidence of this cancer worldwide. HPV vaccination should decrease the incidence further in coming years. Adenocarcinoma of the cervix is also caused by HPV transformation of the endocervical cells but is less common than SCC and is not easily detected by Pap testing (see eBook Figure 8-4B).

   Clinical Presentation

Cervical carcinoma is usually seen in women in their 40s and 50s but may occur as early as the mid-20s if there is a history of early sexual activity and multiple partners. It is more likely in patients who have never been screened or who have not had a Pap test in the previous 5 years. Patients may be asymptomatic or present with abnormal or postcoital bleeding or vaginal discharge that may be watery, mucoid, or purulent and malodorous. The presence of pelvic or lower back pain suggests advanced disease. Suspicion should be high in the presence of an abnormal Pap test.

   Laboratory Findings

Pap testing may be performed by conventional smear or liquid methodology (SurePath Liquid-Based Pap Test and ThinPrep Pap Test). Cytology is reported in the Bethesda system as negative, atypical squamous cells (ASCUS), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), squamous cell carcinoma, and atypical glandular cells (AGUS) (see eBook Figure 8-5A–E). A statement on the adequacy of the cellularity for testing is also made.
²

ACOG recommends screening for cervical cancer with cytology (smear or liquid based) and high-risk HPV DNA testing as follows
³
:

   No screening for women younger than 21 years.

   Cytology alone should be performed for women aged 21–29 years.

   HPV and cytology cotesting performed every 5 years for women aged 30–65 years.

   For women with three negative cytology tests or two negative cotesting screens, no further screening is necessary after age 65 years.

   Women with a history of treated CIN 2, CIN 3, or adenocarcinoma in situ should continue routine age-based screening for at least 20 years.