Extension of useful reagent shelf life beyond manufacturers' recommendations. Cell Markers Committee of the College of American Pathologists.

OBJECTIVE: The College of American Pathologists Cell Markers Committee designed a study to evaluate the use of immunohistochemistry primary antibodies beyond manufacturers' recommended dates. METHODS: Pathologists were asked to save aliquots of primary antibodies during mid-1997 so that by spring 1998 the reagents would be "outdated" according to manufacturers' recommendations. Three tumors were immunostained both in mid-1997 and early 1998 (using outdated reagents in 1998). Two hundred twenty-one laboratories participated. PATIENT SAMPLES: Immunostained materials consisted of an angiomyolipoma immunostained for muscle-specific actin and HMB-45, a melanoma immunostained for S100 protein and HMB-45, and a large cell lymphoma immunostained for common leukocyte antigen and HMB-45. Blocks from the same tumor were used in each instance. MAIN OUTCOME MEASURE: We compared the immunostaining results as a percentage of laboratories indicating a positive or negative immunohistochemical result between the 1997 and 1998 time points. RESULTS: Only minor differences were identified for the 221 reporting laboratories in 1998 as compared with those in 1997. CONCLUSIONS: The data suggest review of the Health Care Financing Administration's ruling on extending the useful reagent shelf life beyond manufacturers recommendations. Similar studies using more inherently quantitative methodology are suggested.

Solitary peripheral papilloma of the breast: a radiologic-pathologic correlation of a benign lesion that may mimic breast cancer on mammography.

OBJECTIVE: The objective of this study was to describe the mammographic appearance with pathologic correlation of solitary peripheral papillomas of the breast. CONCLUSION: Solitary peripheral papillomas of the breast are benign lesions that may present mammographic features suggestive of carcinoma. Solitary peripheral papilloma is a variant related to the solitary central duct papilloma but has a different mammographic appearance because of its location and histologic architecture. The associated risk of malignancy is unclear.

Enteropathy-associated T cell lymphoma with brain involvement.

In a patient with enteropathy-associated T cell lymphoma. there was dissemination to the brain manifesting as an inflammatory lesion. the intestinal and brain lesions were studied using routine histology, immunohistochemistry, and polymerase chain reaction. The jejunum was involved by a multifocal large cell lymphoma associated with multiple inflammatory ulcers and villous atrophy with crypt hyperplasia of the intervening mucosa. The lesion in the brain consisted of necrotic tissue associated with an infiltrate of histiocytes and a relatively scant infiltrate of primarily small lymphocytes. The appearance was that of an inflammatory rather than a neoplastic process. The intestinal lymphoma cells were positive for T cell markers and contained cytotoxic granules detected with the TIA-1 monoclonal antibody. The small lymphocytes and occasional large cells in the cerebral lesion showed the same immunophenotype. DNA extracted from the intestinal lymphoma and the cerebral lesion showed identical monoclonal rearrangement of the TCR-gamma gene. Dissemination from enteropathy-associated T cell lymphoma may masquerade as an inflammatory lesion. Molecular analysis is useful in confirming the diagnosis.

Basal cell carcinoma of the penis.

We report the case of an 87-year-old man with basal cell carcinoma (BCC) of the penis. Treatment was by excisional biopsy and there was no recurrence after thirty-four months. Although BCC is a common skin tumor, it rarely occurs on the penis. A review of the literature shows that most penile BCCs occur on the shaft in older men, have been present for more than a year, and are successfully treated with excisional biopsy. This is the nineteenth reported case of BCC of the penis and represents the oldest patient reported to date.

Factitial illness mimicking rheumatic disease with panniculitis.

Factitial disorders can present with a wide spectrum of clinical features and might be overlooked. We identified two patients believed to have factitial disorders mimicking panniculitis at one medical center within 15 months. Both were females in their early forties who had long histories of cutaneous ulcerations, recurrent cellulitis, abscesses, atrophy, and scarring with sparing of inaccessible body areas. They had a) undergone surgical interventions during multiple hospitalizations, b) demonstrated no response to apparently appropriate medical management, c) had thick charts, clinical depression, "hollow" histories, and borderline personalities, and d) exhibited "peregrination" and "laparotomaphilia migrans." Their biopsies suggested amorphous birefringent material of exogenous origin on polarized light microscopy. Factitial disease is an underrecognized clinical syndrome. This diagnosis can be established when it is considered and when thoughtful evaluation is undertaken; this disorder may be amendable to management if patients return for care.

Endoscopically removed malignant colorectal polyps: clinicopathologic correlations.

BACKGROUND/AIMS: Treatment options for patients with endoscopically removed malignant colorectal polyps are polypectomy alone vs. polypectomy followed by surgery. The aim of this study was to define histopathologic parameters that can be used for clinically relevant treatment decisions. METHODS: Five pathologists evaluated 140 polyps for the presence or absence of unfavorable histology. Unfavorable histology was tumor at or near (< or = 1.0 mm) the margin and/or grade III and/or lymphatic and/or venous invasion. Adverse outcome was recurrent and/or local cancer and/or lymph node metastasis. RESULTS: Adverse outcome was 19.7% (14 of 71), 8.6% (2 of 23), and 0% (0 of 46) when unfavorable histology was present, indefinite (lack of agreement), and absent, respectively (P < 0.0005, present vs. absent). Four patients with cancer > 1.0 mm from the margin had an adverse outcome (2 with lymphatic invasion and 2 indefinite for lymphatic invasion). Four patients with negative resections later developed distant metastases. Eight patients (6.3%) died of disease, and 2 of 69 without unfavorable histology (both indefinite for lymphatic invasion) had an adverse outcome. Interobserver strength of agreement was substantial to almost perfect for margin, grade, and venous invasion and fair to substantial for lymphatic invasion. CONCLUSIONS: This system is usable clinically. Patients with unfavorable histology are probably best managed by resection postpolypectomy, whereas in the absence of unfavorable histology, they probably can be treated by polypectomy only.

Cutaneous metastases from carcinoma of the ovary.

Cutaneous metastases from ovarian carcinoma are very uncommon. Two cases are presented that demonstrate the typical clinical features of this rare complication of advanced ovarian cancer. Through recognition of the characteristic appearance and distribution of the lesion, the physician may suspect the diagnosis based on clinical examinations.

Pure seminoma arising in androgen insensitivity syndrome (testicular feminization syndrome): a case report and review of the literature.

This is a case of a young woman who had testicular feminization syndrome and developed a seminoma in an undescended intrapelvic testis. Androgen insensitivity (testicular feminization) syndrome is a rare inherited form of male pseudohermaphroditism that occurs in phenotypically normal women with adequate breast development, normal external genitalia, a vagina of variable depth, absent uterus, and sparse or absent pubic and axillary hair. The gonad (undescended testes) may be intraabdominal, inguinal, or labial. These patients characteristically have male karyotype (XY) and negative sex chromatin and are at increased risk of undergoing malignant transformation of the undescended gonad. We review the literature emphasizing the biochemical and endocrinologic abnormalities leading to the syndrome, as well as the morphologic abnormalities (light microscopic) of the undescended testes, diagnosis, and therapeutic management.

Quality assurance goals in surgical pathology.

The development, implementation, and evaluation of quality assurance programs for surgical pathology present special challenges, largely because of the subjective and consultative nature of the "test result" (the diagnostic report). The primary objective of quality assurance is the generation of an accurate, timely, and clinically relevant diagnostic report based on the interpretation of optimal technical preparations. This article defines the essential elements of a comprehensive quality assurance program for anatomic pathology, reviews the role of accrediting agencies in evaluating quality assurance, and describes the various contributions of professional organizations that may influence the achievement of our quality assurance goals. The major emphasis is on those activities that affect the quality of the "outcome" (completed diagnostic report) in surgical pathology and assess its contribution to patient management.

Crohn's disease-associated carcinoma. A poorly recognized complication of inflammatory bowel disease.

We have reviewed eight cases of Crohn's disease associated carcinoma (CDAC) of the bowel treated at Saint Barnabas Medical Center since 1977. Five patients had colorectal carcinoma in areas of dysplasia within histologically recognizable Crohn's disease. One of the large bowel carcinomas was a diffusely infiltrating signet ring adenocarcinoma (linitis plastica), three were mucinous carcinomas, and one contained both cell types. Survival ranged from 4 to 55 months. Three patients developed ileal carcinomas in areas of dysplasia within histologically recognizable Crohn's disease. One of the ileal cancers was a moderately differentiated adenocarcinoma; two were poorly differentiated adenocarcinomas. Survival ranged from 8 to 44 months. The dysplastic changes seen in the bowel adjacent to the tumors in these patients were identical to the characteristic pre-cancerous (dysplastic) changes well described in ulcerative colitis. The histopathologic changes seen in this high-risk group of patients are also similar to those of previously reported CDAC. Those patients with the more diffuse dysplastic changes might have been detected before the development of invasive cancer had they undergone periodic colonoscopic surveillance. One patient in the series with an asymptomatic lesion was, in fact, identified at surveillance colonoscopy. It would appear that Crohn's disease patients have a similar risk for carcinoma previously recognized in ulcerative colitis patients and that surveillance protocols should be developed for this group of patients.

Intralaboratory quality assurance of immunohistochemical procedures. Recommended practices for daily application.

During the past several decades, immunohistologic techniques have been developed that may provide important adjunctive information to the diagnostic pathologist. These procedures are now widely available and commonly used in the pathology laboratory. Proper performance of immunohistochemical procedures and interpretation of their results require development and implementation of appropriate quality control and quality assurance measures. This article reviews the application of quality control standards in the immunohistochemistry laboratory and the integration of these activities into the overall quality assurance program of the department.

Interlaboratory variability of immunohistochemical stains. Results of the cell markers survey of the College of American Pathologists.

Immunohistochemical techniques have become commonplace adjunctive aids in anatomic pathology. Although much has been written describing modifications of the basic techniques, sensitivity, and specificity of reagents, little has been published regarding the interlaboratory variability in immunostain results on a given test sample. The Cell Markers Survey of the College of American Pathologists was organized to address this question of interlaboratory variability and to disseminate information on the techniques and reagents currently available.

Intracystic papillary breast carcinoma in a 55-year-old man: radiologic and pathologic correlation.

Radiographic manifestation of intracystic papillary male carcinoma is presented along with its histopathological correlation. The prognosis, differential diagnosis, and natural history as well as possible sites of origin are discussed.

Colonic involvement in angioimmunoblastic lymphadenopathy resembling inflammatory bowel disease.

A woman 68 years of age had fever, malaise, diffuse lymphadenopathy, splenomegaly followed by abdominal pain, and diarrhea. A lymph node biopsy specimen showed nonspecific follicular hyperplasia. Symptoms were responsive initially to prednisone. Recurrent symptoms warranted colonic biopsy, which was consistent with Crohn's disease, and were responsive partially to prednisone and azulfidine. Because of progressive deterioration, a repeat lymph node biopsy was performed and showed the characteristic histologic feature of angioimmunoblastic lymphadenopathy (AILD). The evolution of the histopathologic features of the case is discussed, and gastrointestinal (GI) manifestations of AILD are reviewed. Although the GI tract is an unusual site for extra nodal AILD, colonic involvement can imitate the clinical and histologic features of inflammatory bowel disease.

Malignant disseminated porokeratosis.

A patient has been observed with a distinct form of disseminated porokeratosis. During the course of his disease, he developed changes in the porokeratosis lesions that included cellular atypia, dysplasia, and invasive squamous cell carcinoma. One of the squamous cell carcinomas produced regional and disseminated metastases, resulting in the death of the patient. Although malignancy has been previously described in the various types of porokeratosis, this is the first report of disseminated metastases and death in any form of this disease.

Quality assurance in anatomic pathology.

Comprehensive quality assurance in anatomic pathology must address several levels of laboratory operation: procedural/technical issues, the quality of the diagnostic report, and the medical consultative role of the pathologist. Procedural/technical quality control in anatomic pathology differs very little from that practiced in the various sections of clinical pathology. Assessment of the quality of the final report is a major responsibility of the pathologist who renders the diagnosis. Guidelines that systematically address such issues as specimen handling and the content of the diagnostic report are effective in promoting consistency, completeness, and the clinical relevance of the information provided. Quality assessment of the pathologist's consultative role is more difficult to define and implement. However, systematic evaluation and correlative review of all available diagnostic information, appropriate use of consultation and case review, and participation in continuing education and self-assessment activities all may contribute to and help document the quality of services provided. It is important to emphasize the value of flexibility in designing a comprehensive quality assurance program for anatomic pathology. Departments differ markedly in characteristics such as staff size, subspecialty interests, teaching commitments, and volume and type of case material. Nevertheless, the general principles of written organization, systematic monitoring, and documentation of adherence to the program should be followed. Just as the design of the program may benefit from flexibility, the laboratory should be prepared to modify its quality control and assurance techniques and implement corrective measures should surveillance identify problems such as frequent typographic errors, inadequate diagnostic information, or deterioration in correlation between frozen section and final diagnoses. The ultimate objective of all of these efforts is to provide the referring physician with an accurate, clinically relevant diagnostic report, thereby enhancing the pathologist's role as a valued medical consultant.