Pseudoangiomatous stromal hyperplasia (PASH) of the breast with foci of morphologic malignancy: a case of PASH with malignant transformation?

Pseudoangiomatous stromal hyperplasia (PASH) is a benign proliferation of the hormonally responsive, specialized mammary stroma characterized by slit-like pseudovascular spaces lined by bland spindle cells. It is usually an incidental microscopic finding but in some cases it may present as a slowly growing mass. A malignant counterpart for this lesion has not been reported. We describe a case of PASH with foci of malignant histologic features presenting as a slowly growing mass in a 30-year-old woman. The previously reported variants of PASH and the other mammary stromal lesions related to PASH are also discussed. This is perhaps the first case of PASH with foci of malignant histologic features reported in the literature and represents a rare sarcoma derived from specialized hormonally responsive mammary stroma.

Collagen alpha1(XI) in normal and malignant breast tissue.

Little is known about collagen XI expression in normal and malignant breast tissue. Tissue microarrays, constructed from 72 patients with breast carcinoma and matched normal tissue, were immunohistochemically stained with five antisera against isoform-specific regions of collagen alpha1(XI) N-terminal domain. Staining intensity was graded on a 0-3 scale in epithelial cytoplasm, stroma, and endothelial staining of the vasculature of each tissue core. The staining was compared to known pathologic parameters: age, tumor size, overall tumor grade, nuclear grade, tubule formation, mitotic counts, angiolymphatic invasion, node status, estrogen receptor status, progesterone receptor status, and HER-2/neu status. Estrogen and progesterone receptor status were used as a control for comparison. With antisera V1a and amino propeptide (Npp), stroma surrounding cancerous cells was found to have decreased collagen alpha1(XI) staining compared to stroma adjacent to normal epithelium (P=0.0006, P<0.0001). Collagen alpha1(XI) staining with V1a antiserum in cytoplasm of cancer cells demonstrated decreased intensity in metastasized primary tumors when compared to nonmetastasized primary tumors (P=0.009). Cytoplasmic staining with Npp antiserum in cancer demonstrated an inverse relationship to positive estrogen receptor status in cancer (P=0.012) and to progesterone receptor status (P=0.044). Stromal staining for Npp in cancerous tissue demonstrated an inverse relationship with tubule formation score (P=0.015). This is the first study to localize collagen XI within normal and malignant breast tissue. Collagen alpha1(XI) appears to be downregulated in stroma surrounding breast cancer. Detection of collagen XI in breast tissue may help predict women who have lymph node metastases.

Immunohistochemical localization of collagen type XI alpha1 and alpha2 chains in human colon tissue.

In previous studies, collagen XI mRNA has been detected in colon cancer, but its location in human colon tissue has not been determined. The heterotrimeric collagen XI consists of three alpha chains. While it is known that collagen XI plays a regulatory role in collagen fibril formation, its function in the colon is unknown. The characterization of normal human colon tissue will allow a better understanding of the variance of collagen XI in abnormal tissues. Grossly normal and malignant human colon tissue was obtained from pathology archives. Immunohistochemical staining with a 58K Golgi marker and alpha1(XI) and alpha2(XI) antisera was used to specifically locate their presence in normal colon tissue. A comparative bright field microscopic analysis showed the presence of collagen XI in human colon. The juxtanuclear, dot-like collagen XI staining in the Golgi apparatus of goblet cells in normal tissue paralleled the staining of the 58K Golgi marker. Ultra light microscopy verified these results. Staining was also confirmed in malignant colon tissue. This study is the first to show that collagen XI is present in the Golgi apparatus of normal human colon goblet cells and localizes collagen XI in both normal and malignant tissue. Although the function of collagen XI in the colon is unknown, our immunohistochemical characterization provides the foundation for future immunohistopathology studies of the colon.

The role of second opinion pathology in the management of lesions of the head and neck.

PURPOSE OF REVIEW: Medical error is a common problem, and its human cost in terms of disability, suffering, and death is stunning. Steps toward reducing medical error will require the identification of mistake-prone practices within a complex health care system. Erroneous pathologic diagnosis has been identified as one source of error. This review was undertaken to assess the magnitude of diagnostic imprecision in lesions of the head and neck, and to address the validity of mandatory review of pathology material for patients who are referred from one institution to another for management of tumors involving the head and neck. RECENT FINDINGS: Mandatory second opinion pathology consistently uncovers discrepancies across all major organ systems and has a profound impact on management and prognosis. Site-specific studies have implicated the head and neck as a high-risk area that is prone to diagnostic error. Diagnostic discrepancy rates have ranged from 1 to 53% for surgical pathology studies and from 17 to 60% for cytopathology studies. Major changes (affecting treatment or prognosis) occur in 5 to 7% of surgical pathology cases. The thyroid is consistently identified as a site that is particularly prone to diagnostic discrepancies; and no specific head and neck sites are immune to diagnostic error. SUMMARY: Limited studies addressing the site-specific impact of second opinion pathology implicate the head and neck as a high-risk area that is prone to major changes in diagnoses. Accordingly, mandatory second opinion pathology makes good clinical and risk management sense for all patients referred to head and neck surgery or oncology services before a major therapeutic endeavor is undertaken.

Lesions missed on prostate biopsies in cases sent in for consultation.

BACKGROUND: There are no reports on how often lesions are missed on prostate needle biopsies. METHODS: Over a 10-month period, 8/99 to 5/00, 3,251 prostate biopsy cases were seen in consultation. RESULTS: We identified 87 (2.7%) patients with missed lesions (n = 9 academic hospitals; n = 44 community hospitals; n = 34 commercial labs). Overall, 119 lesions were missed in 87 patients. Missed lesions were as follows: small atypical glands suspicious for cancer (41 lesions in 35 patients), prostatic adenocarcinoma (39 cancers in 32 patients), high grade prostatic intraepithelial neoplasia (HGPIN) (34 lesions in 30 patients), and HGPIN with adjacent small atypical glands (five lesions in five patients)--some men with more than one type of missed lesion. Detection of the missed lesions would have resulted in either: a definite change in care in 15 of 3,251 (0.5%) patients or a possible change in care (bilateral cancer vs. unilateral cancer; HGPIN vs. atypical) in 17 (0.5%) patients. In 21 (24%) of the cases, the slides were seen by at least two pathologists prior to consultation at our hospital. CONCLUSIONS: Although the number of prostate biopsies with missed lesions in a consult-based population of prostate biopsies appears relatively high (2.7%), the detection of the missed lesions would have only effected a definite change in care in 0.5% of all patients or a possible change in care in another 0.5% of patients. Our data underestimates missed lesions, as the entire specimen was not submitted for review in 41% of cases. Although our incidence of missed lesions gives some indication as to the magnitude of the problem, it cannot be equated with the risk of missing lesions in unselected cases.

The impact of second opinion surgical pathology on the practice of head and neck surgery: a decade experience at a large referral hospital.

BACKGROUND: A second review of histopathologic diagnoses is a quality assurance practice that helps expose diagnostic errors and guide management of patients being referred from outside hospitals. Identification of anatomic regions and specimen types that are prone to diagnostic error will be helpful in guiding policy decisions regarding mandatory second opinion surgical pathology. METHODS: All available outside pathology reports were retrieved for patients referred to The Johns Hopkins Hospital Department of Otolaryngology-Head and Neck Surgery between January 1, 1990, and January 1, 2000. The outside diagnosis was compared with diagnosis rendered at the referral hospital. A discrepant diagnosis was regarded as any change resulting in a significant modification in therapy or prognosis. RESULTS: Of the 814 cases reviewed, the second opinion surgical pathology diagnosis resulted in 54 (7%) changed diagnoses. Of the changed diagnosis, 13 (24%) involved a change from a benign to a malignant diagnosis; 8 (15%) involved a change from a malignant to a benign diagnosis; and 33 (61%) involved a change in tumor classification. Follow-up information supported the second opinion diagnosis in 41 of 43 cases (95%). CONCLUSIONS: In a consequential number of cases, second opinion surgical pathology results in major therapeutic and prognostic modifications for patients sent to large referral hospitals for head and neck oncologic surgery.