ng-Xi L. Li

Outcome in 846 Cutaneous Melanoma Patients From a Single Center After a Negative Sentinel Node Biopsy

BackgroundA negative sentinel node biopsy (SNB) implies a good prognosis for melanoma patients. The purpose of this study was to determine the long-term outcome for melanoma patients with a negative SNB.MethodsSurvival and prognostic factors were analyzed for 836 SNB-negative patients. All patients with a node field recurrence were reviewed, and sentinel node (SN) tissue was reexamined.ResultsThe median tumor thickness was 1.7 mm, and 23.8% were ulcerated. The median follow-up was 42.1 months. Melanoma specific survival at 5 years was 90%, compared with 56% for SN-positive patients (P < .001). On multivariate analysis, only thickness and ulceration retained significance for disease-free and disease-specific survival. Five-year survival for patients with nonulcerated lesions was 94% vs. 78% with ulceration. Eighty-three patients (9.9%) had a recurrence. Twenty-seven patients developed recurrence in the regional node field, and in 22 of these, it was the first recurrence site. Six developed local recurrence, 17 an in-transit metastasis, and 58 distant disease. The false-negative rate was 13.2%. SN slides and tissue blocks were further examined in 18 patients with recurrence in the node field, and metastatic disease was found in 3 of them.ConclusionsThis large, single-center study confirms that patients with a negative SNB have a significantly better prognosis than those with positive SNs. In those with a negative SNB, primary tumor thickness and ulceration are independent predictors of survival. Incorrect pathologic diagnosis contributed to only a minority of the false-negative results in this study.

A zonal comparison of MIB1-Ki67 immunoreactivity in benign and malignant melanocytic lesions

Differentiation between malignant melanomas and benign nevi can sometimes be difficult by conventional histopathology, and additional diagnostic markers may be helpful. This study investigated the immunoreactivity of the cell proliferation marker MIB1-Ki67 in 23 compound nevi, 17 dysplastic nevi, 8 Spitz nevi (SN), and 24 malignant melanomas (MMs) and evaluated its ability in separating benign nevi from MMs. In each lesion, the average number (percentage) of MIB1-positive nuclei (%MIB1-Mean) and the maximal number (percentage) of MIB1-positive nuclei (%MIB1-Max) were determined from each of the superficial, middle, and deep dermal zones of the lesion as well as from the entire lesion. The %MIB1-Max was determined from subjectively selected area(s) of high count. Malignant melanomas had a significantly greater %MIB1-Mean and %MIB1-Max than all benign nevi in all individual zones and in the entire lesion (p < 0.05). Discriminant analysis showed that the %MIB1-Mean and %MIB1-Max counted from the whole lesions had better discriminating abilities than from the individual zones. By using the %MIB1-Mean from all zones, all lesions except 1 SN and 3 MMs could be correctly classified as benign or malignant. When using the %MIB1-Max from all zones, all but 2 SN could be correctly separated as benign or malignant. Thus, MIB1-Ki67 immunoreactivity closely correlates with the benignancy or malignancy of melanocytic lesions and may assist in the differentiation of benign nevi from MMs.

Micromorphometric features of positive sentinel lymph nodes predict involvement of nonsentinel nodes in patients with melanoma.

The aim of the present study was to determine whether micromorphometric features of positive sentinel lymph nodes (SLNs) from patients with melanoma are useful for predicting further nodal involvement in completion lymph node dissection (CLND) specimens. Of 986 patients with melanoma undergoing SLN biopsy between March 1992 and February 2001, 175 (17.7%) had at least 1 positive SLN and 140 had subsequent CLND specimens available for review. Further nodal involvement in CLND specimens was present in 24 (17.1%) of 140 patients. Of 8 micromorphometric features of the SLNs that were assessed, the presence of metastases in CLND specimens was correlated significantly with a tumor penetrative depth (maximum distance of melanoma cells from the inner margin of the SLN capsule) of more than 2 mm (P < .05), a deposit size of more than 10 mm2 (P < .01), the presence of melanoma cells in perinodal lymphatic vessels (P < .01), and the effacement of nodal architecture by metastatic melanoma cells (P < .05). Our results indicate that some morphologic features of melanoma metastases in SLNs predict the likelihood of further nodal involvement in CLND specimens.

Pathologic review of negative sentinel lymph nodes in Melanoma patients with regional recurrence: A clinicopathologic study of 1152 patients undergoing sentinel lymph node biopsy

A sentinel lymph node (SLN) that is melanoma negative by pathologic examination implies absence of melanoma metastasis to that regional lymph node field. However, a small proportion of patients develop regional node field recurrence after a negative SLN biopsy. In this study, we reviewed the histopathology of negative SLNs from such patients to determine whether occult melanoma cells were present in the SLNs, to characterize the pathologic features of false-negative SLNs, and to provide recommendations for the histopathologic examination of these specimens. Between March 1992 and June 2001, of 1152 patients who had undergone SLN biopsy for primary melanomas at the Sydney Melanoma Unit, 976 were diagnosed with negative SLNs by initial pathologic examination (using 2 hematoxylin and eosin stained sections, and 2 immunostained sections for S-100 protein and HMB45), and follow-up was available in 957. Of these, 26 (2.7%) developed regional lymph node recurrence during a median follow-up period of 35.7 months. For 22 of them, the original slides and tissue blocks were available for reexamination. The original slides of each block were reviewed. Multiple further sections were cut from each block and stained with hematoxylin and eosin, for S-100, HMB45, and Melan A. Deposits of occult melanoma cells were detected in 7 of the 22 cases (31.8%). In 5 of the 7 cases, deposits of melanoma cells were present only in the recut sections. There were no significant differences in clinical and pathologic variables for those patients in whom occult melanoma cells were found by pathologic reexamination of their SLNs, compared with those in whom no melanoma cells were detected. The detection of melanoma cell deposits in only 7 of 22 false-negative SLNs suggests that mechanisms other than failure of histopathologic examination may contribute to the failure of the SLN biopsy technique in some patients. The failure rate for melanoma detection in SLNs by our routine pathologic examination, using the current protocol at our institution, was <1% (7 of 957 patients). Routinely performing more intensive histopathologic examination of SLNs is difficult to justify from a cost benefit perspective; we therefore recommend examining two hematoxylin and eosin stained sections and two immunostained sections (for S-100 and HMB45) routinely on SLNs from melanoma patients.

False Negative Sentinel Lymph Node Biopsies in Melanoma May Result From Deficiencies in Nuclear Medicine, Surgery, or Pathology.

Objective:To investigate a cohort of melanoma patients with false negative (FN) sentinel node (SN) biopsies (SNBs) to identify the reasons for the FN result. Summary of Background Data:SNB is a highly efficient staging method in melanoma patients. However, with long-term follow-up FN SNB results of up to 25% have been reported. Methods:Seventy-four SNs from 33 patients found to have had an FN SNB were analyzed by reviewing the lymphoscintigraphy, surgical data, and histopathology, and by assessing nodal tissue using multimarker real-time quantitative reverse transcription (qRT) polymerase chain reaction, and antimony concentration measurements (as a marker of “true” SN status) using inductively coupled plasma mass spectroscopy. Results:Nine SNs (12%) from 9 patients (27%) had evidence of melanoma on histopathologic review. Twelve SNs (16%) from 10 patients (30%) were qRT(+). Four of these 12 SNs were positive on histopathology review and 8 were negative. Four patients (12%) were upstaged by qRT. Sixteen patients had their SNB histology, lymphoscintigraphy, and surgical data reviewed. Identifiable causes of the FN SNBs were not found after review of all modalities in 4 patients. SNs from all 4 patients had antimony levels indicative of an SN. Of the SNs evaluable by qRT, 1 was qRT(+) and 7 SNs from 2 patients were qRT(−). Conclusions:An FN SN can occur because of deficiencies in nuclear medicine, surgery, or pathology. qRT can detect “occult” metastatic melanoma in SNs that have been identified as negative by histopathology.

Morphologic Features of Melanophages Under In Vivo Reflectance Confocal Microscopy

OBJECTIVES To determine morphologic features of melanophages under in vivo reflectance confocal microscopy (RCM) and to highlight morphologic features that are important in distinguishing melanophages from melanocytes. DESIGN Consecutive retrospective study. SETTING Referral center for pigmented lesions. PATIENTS The study group retrospectively constituted 20 consecutive patients having biopsy-proven lichen planus-like keratoses that dermoscopically and histopathologically showed many melanophages and that had been imaged under RCM before biopsy. MAIN OUTCOME MEASURES The RCM characteristics of isolated dermal bright cells were scored blinded to dermoscopic features and histopathologic diagnosis. RESULTS Under RCM, melanophages were significantly smaller than melanocytes (mean [SD] cell diameter, 13.6 [1.6] vs 18.2 [2.9] microm, P = .006). Nuclei (intracellular low-reflectance round-oval structures) were visible in only 16% (29 of 184) of the cells in melanophages vs 57% (28 of 49) of the cells in melanocytes (P < .001). When identified, nuclei were smaller in melanophages than in melanocytes (mean [SD] diameter, 3.2 [1.2] vs 6.4 [0.7] microm, P < .001). Compared with melanocytes, melanophages were significantly more ill defined (76% [140 of 184] vs 18% [9 of 49], P < .001), less round (23% [42 of 184] vs 69% [34 of 49], P < .001), and less dendritic (1% [2 of 184] vs 12% [6 of 49]) (P = .001). CONCLUSION Observed differences in morphologic features should enable distinction between melanophages and melanocytes under RCM, thereby improving the accuracy of skin lesion diagnosis using this technique.

Failure to remove true sentinel nodes can cause failure of the sentinel node biopsy technique: Evidence from antimony concentrations in false-negative sentinel nodes from melanoma patients

We have recently found that antimony (originating from the technetium 99m antimony trisulfide colloid, used for preoperative lymphoscintigraphy) can be measured in tissue sections from archival paraffin blocks of sentinel nodes (SNs) by means of inductively coupled plasma mass spectrometry (ICP-MS) to confirm that removed nodes are ture SNs. We performed a retrospective analysis of antimony concentrations in all our false-negative (FN) SNs to determine whether errors in lymphadenectomy (i.e., failure to remove true SNs) may be a cause of FN SN biopsies (SNBs). Among 27 patients with an FN SNB, metastases were found on histopathologic review of the original slides or additional sections in 7 of 23 patients for which they were available; however, antimony concentrations were low in 5 of 20 presumptive SNs. Our results suggest that an FN SNB can occur because of failure to remove the true SN as well as histopathologic misdiagnosis.

Argyrophilic Staining of Nucleolar Organizer Region Count and Morphometry in Benign and Malignant Melanocytic Lesions

Differentiation between malignant melanomas (MMs) and benign nevi based on histologic features can sometimes be difficult. This study evaluated the diagnostic effectiveness of argyrophilic staining of nucleolar organizer regions (AgNORs) in separating benign nevi from MMs by assessing 27 compound nevi (CN), 20 dysplastic nevi (DN), 10 Spitz nevi (SN), and 24 MMs. Both AgNOR count and morphology variables were measured from the superficial, middle, and deep zones of the lesions using video image analysis. Malignant melanomas had a significantly greater AgNOR number per nucleus, mean AgNOR area per nucleus, and variation in AgNOR area per nucleus compared with all types of benign nevi (p < 0.05). In multivariate discriminant analysis using a combination of four AgNOR counts and morphometric parameters, all CN and DN, 8 of 10 SN, and 23 of 24 MMs could be correctly classified as benign or malignant. The results suggest that both AgNOR count and morphology help to separate benign and malignant melanocytic lesions and that the combination of both sets of parameters improves their discriminating ability.

Parachordoma is not distinguishable from axial chordoma using immunohistochemistry

Parachordoma is a rare soft tissue tumor that morphologically resembles chordoma of the axial skeleton but occurs in a peripheral site. A recent study reported immunohistochemical differences between chordoma and parachordoma. While both tumors were positive for cytokeratin (CK) 8/18 (as recognized by the antibody Cam5.2), S100 and epithelial membrane antigen (EMA), only the chordoma was positive for CK7, CK20, CK 1/5/10/14 (as recognized by the antibody 34βE12) and carcinoembryonic antigen (CEA). It has since been suggested that tumors indistinguishable from chordoma that involve the periphery should be termed chordoma periphericum and that these tumors are distinct from parachordoma. In the current study, the clinical, radiological, pathological, immunohistochemical and ultrastructural features of a chordoma‐like tumor involving the deep soft tissues of the lower leg of a 69‐year‐old woman are presented. Microscopically, the tumor had a pseudolobulated growth pattern and consisted of sheets, nests and cords of epithelioid cells, some with a physaliferous appearance, separated by abundant myxoid stroma. The tumor cells were positive for CK 8/18, EMA and S100, showed focal staining for CK7, and were negative for CK20, CK 1/5/10/14 and CEA. On the basis of these results a diagnosis of parachordoma was favored. For comparison, an immunohistochemical analysis of five axial chordomas was also performed. The chordomas showed positivity for CK 8/18 (5 of 5 cases), EMA (5 of 5 cases), S100 (5 of 5 cases), CK 1/5/10/14 (1 of 5 cases) and CK7 (1 of 5 cases). Stains for CK20 and CEA were negative in all five chordomas. The results of the present study suggest that the expression of antigens for CK 1/5/10/14, CK7, CK20 and CEA in chordoma might not be as common as what has been previously reported. The results also suggest that parachordoma might not be easily distinguished immunohistochemically from axial chordoma (and therefore also from so‐called chordoma periphericum).

Antimony by ICP-MS as a marker for sentinel lymph nodes in melanoma patients

A sensitive, accurate and specific method for the analysis of antimony by ICP-MS is presented as a marker of the sentinel lymph node in melanoma patients.