Cutaneous involvement by Burkitt lymphoma.
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Biopsy↗
Biomedical subjects
John S Metcalf
Publications and source records attributed to John S Metcalf.
Langerhans cell sarcoma.
Proliferations of Langerhans cells can be histologically divided into cytologically benign Langerhans cell proliferations, which include the clinical syndromes of Langerhans cell histiocytosis, and cytologically malignant Langerhans cell sarcoma. We report a Langerhans cell sarcoma in a 33-year-old male that arose on the posterior thigh with subsequent regional lymph node involvement. Conventional microscopic, immunohistochemical, and ultrastructural analysis confirmed Langerhans cell differentiation. Aberrant CD31 expression, similar to that described previously in Langerhans cell histiocytosis, was prominent in this tumor, possibly enhancing its migratory capabilities.
Adult↗
Histologic patterns of polyethylene glycol-liposomal doxorubicin-related cutaneous eruptions.
Polyethylene glycol (PEG)-liposomal doxorubicin (Stealth R, Doxil) is a formulation of doxorubicin, which is encapsulated in liposomes formulated with PEG. It is favored in the palliative setting over doxorubicin because of its generally favorable side effect profile. Adverse reactions are predominantly skin eruptions. We report 3 cases of women with breast cancer undergoing treatment with liposomal doxorubicin who developed palmar-plantar erythrodysesthesia and diffuse morbilliform eruptions. Biopsies in the 2 cases demonstrated vacuolar interface dermatitis with epidermal dysmaturation and the third case suggested a drug eruption. Additionally, we report a woman with metastatic breast cancer who developed a similar morbilliform eruption soon after completing a regimen of liposomal doxorubicin. The biopsy revealed an atypical squamous proliferation showing epidermal dysmaturation with focal evidence of interface damage. Both clinician and pathologist alike should be cognizant of this cutaneous eruption, as well as the histologic patterns.
Adult↗
Can scleromyxedema be differentiated from nephrogenic fibrosing dermatopathy by the distribution of the infiltrate?
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Diagnosis, Differential↗
An innovative microarray strategy identities informative molecular markers for the detection of micrometastatic breast cancer.
There is increasing evidence that molecular detection of micrometastatic breast cancer in the axillary lymph nodes (ALN) of breast cancer patients can improve staging. Molecular analyses of samples obtained from the Minimally Invasive Molecular Staging of Breast Cancer Trial (n = 489 patients) indicate that whereas the majority of molecular markers are informative for the detection of metastatic breast cancer (significant disease burden), only a few are sensitive for the detection of micrometastatic disease (limited disease burden). Frequency distribution and linear regression analyses reveal that relative levels of gene expression are highly correlated with apparent sensitivity for the detection of micrometastic breast cancer (P < 0.05). These data provides statistical validation of the concept that the most informative markers for detection of micrometastatic disease are those that are most highly expressed in metastatic disease. To test this hypothesis, we developed an innovative microarray strategy. RNA from a metastatic breast cancer ALN was diluted into RNA from a normal lymph node and analyzed using Affymetrix microarrays. Expression analysis indicated that only two genes [mammaglobin (mam) and trefoil factor 1 (TFF1)] were significantly overexpressed at a dilution of 1:50. Real-time reverse transcription-PCR analysis of pathology-negative ALN (n = 72) confirm that of all the markers tested, mam and TFF1 have the highest apparent sensitivity for detection of micrometastatic breast cancer. We conclude that a dilutional microarray approach is a simple and reliable method for the identification of informative molecular markers for the detection of micrometastatic cancer.
Breast Neoplasms↗
Molecular analysis improves sensitivity of breast sentinel lymph node biopsy: results of a multi-institutional prospective cohort study.
BACKGROUND: Pathologic evaluation may lack the sensitivity required for accurate staging of the axilla in breast cancer patients. We have completed enrollment of a multi-institutional prospective cohort study designed to determine if molecular analyses can improve axillary staging. In subset analyses, we have attempted to address the following questions: (1) Does molecular analysis improve the sensitivity of sentinel lymph node biopsy (SLNB) and (2) is the sentinel lymph node (SLN) hypothesis valid at the molecular level? METHODS: Four hundred eighty-nine subjects with T1, T2, or T3 breast cancer and no evidence of axillary lymph node (ALN) involvement were enrolled. ALNs were analyzed by routine pathology (hematoxylin-eosin staining), and by multimarker real-time reverse transcriptase-polymerase chain reaction analysis CRT-PCR to detect breast cancer metastases. Pathology and molecular data for both SLNs and nonsentinel ALNs were available for a subset of 207 subjects. RESULTS: The sensitivity of pathologic analysis of the SLN to predict the pathologic status of ALNs was 84.1%. The sensitivity of combining pathologic with molecular analysis of the SLN to predict the pathologic status of ALNs was 92.8%, a statistically significant increase in sensitivity (P = .031 by the McNemar test for correlated proportions). Finally, the sensitivity of combining pathologic with molecular analysis of the SLN to predict the pathologic or molecular status of ALNs was 85.4%. CONCLUSIONS: The combination of pathologic and molecular analysis of SLNs resulted in the highest sensitivity for prediction of the pathologic status of ALNs. The data also provide evidence that the SLN hypothesis remains valid at the molecular level.
Bone Marrow↗
Merkel cell carcinoma in situ.
BACKGROUND: Merkel cell carcinoma (MCC) is a dermal small blue-cell tumor that occurs in the elderly on the sun damaged head and neck. Epidermal involvement is unusual and MCC limited to the epidermis is very rare. CASE REPORT: A slightly tender pink hyperkeratotic papule was noted on the dorsal right hand of a 76-year-old man with a history of multiple skin cancers. An intraepidermal proliferation of small blue cells distributed in nests and single units at all levels of the epidermis was found within a solar keratosis and adjacent to an area of squamous cell carcinoma in situ. Cytokeratin 20 and neuron specific enolase highlighted these cells and failed to reveal dermal involvement. There was no residue on re-excision. CONCLUSION: We report the third case of MCC in situ. These lesions have only been reported in association with squamous neoplasms on the extremities.
Aged↗
Molecular detection of micrometastatic breast cancer in histopathology-negative axillary lymph nodes correlates with traditional predictors of prognosis: an interim analysis of a prospective multi-institutional cohort study.
OBJECTIVE: We sought to establish the clinical relevance of micrometastatic disease detected by reverse transcription polymerase chain reaction (RT-PCR) in axillary lymph nodes (ALN) of breast cancer patients. BACKGROUND: The presence of ALN metastases remains one of the most valuable prognostic indicators in women with breast cancer. However, the clinical relevance of molecular detection of micrometastatic breast cancer in sentinel lymph nodes (SLN) and nonsentinel ALN has not been established. METHODS: Four hundred eighty-nine patients with T1-T3 primary breast cancers were analyzed in a prospective, multi-institutional cohort study. ALN were analyzed by standard histopathology (H&E staining) and by multimarker, real-time RT-PCR analysis (mam, mamB, muc1, CEA, PSE, CK19, and PIP) designed to detect breast cancer micrometastases. RESULTS: A positive marker signal was observed in 126 (87%) of 145 subjects with pathology-positive ALN, and in 112 (33%) of 344 subjects with pathology-negative ALN. In subjects with pathology-negative ALN, a positive marker signal was significantly associated with traditional indicators of prognosis, such as histologic grade (P = 0.0255) and St. Gallen risk category (P = 0.022). Mammaglobin was the most informative marker in the panel. CONCLUSION: This is the first report to show that overexpression of breast cancer-associated genes in breast cancer subjects with pathology-negative ALN correlates with traditional indicators of disease prognosis. These interim results provide strong evidence that molecular markers could serve as valid surrogates for the detection of occult micrometastases in ALN. Correlation of real-time RT-PCR analyses with disease-free survival in this patient cohort will help to define the clinical relevance of micrometastatic disease in this patient population.
Adult↗
A testing algorithm for determination of HER2 status in patients with breast cancer.
The HER2 gene is amplified and overexpressed in 25-30% of breast carcinomas. Assessment of HER2 status for prognosis and treatment of breast cancer patients can be performed by immunohistochemistry and/or fluorescence in situ hybridization (FISH). To develop a testing algorithm for HER2 in breast cancers, we used FISH analysis to determine the HER2 gene copy number and immunostaining to detect the p185 protein. Interlaboratory, interobserver, and intermethod variabilities of immunohistochemistry were assessed. In 24 invasive breast carcinomas, the indices of HER2 status obtained by FISH and by a reference laboratory's DAKO HercepTest (immunostain) gave an overall concordance of 96%. The reference laboratory's stained slides were re-interpreted by an in-house panel of pathologists; the interpretation differed in one case. The panel's interpretations were concordant with the FISH results in all 24 cases. Interobserver variability for the panel's immunohistochemistry interpretations was assessed using three different immunostaining methods on 70 slides. The numerical (0-1+, 2+, 3+) scores showed greater variability among observers than did the overall positive/negative results. One pathologist reported inconsistent results in >30% of the slides evaluated. Borderline scoring of 1-2+ was reported in 18 slides (23%) by at least one observer. Incongruent interobserver immunohistochemistry scores, leading to different positive and negative interpretations, were obtained with 5 slides (7%). The majority of consensus positive cases exhibited strong membrane staining (3+). The majority of consensus negative cases scored as 0. Based on these observations, we developed a testing algorithm that maximizes the benefits of FISH and immunohistochemistry, providing physicians with accurate results for appropriate clinical care.
Algorithms↗