Staged margin control techniques for surgical excision of lentigo maligna.

For melanoma in situ (MIS) arising in chronically photodamaged skin (a.k.a. lentigo maligna, LM), the preferred treatment remains surgical excision. Yet, the standard 5-mm margins of excision recommended for other subtypes of MIS have proven insufficient for LM, due to the its indistinct borders. In this report, authors review specialized surgical techniques for the treatment of LM that focus on meticulous assessment of peripheral margins prior to closure (staged margin control) conducted with analysis of either frozen or permanent histologic sections. Techniques utilizing permanent sections include variations of the ''square'', ''perimeter'', and ''contoured'' excisions, and recurrence rates with these techniques are reportedly low based on short-term follow-up. Similarly, Mohs micrographic surgery (MMS) has been reported to be effective in LM, with recurrence rates generally less than 1% over three-five years of follow-up. In order to simplify margin assessment for MMS, many investigators have begun to rely on intraoperative immunohistochemistry (IHC) to identify melanocytes in frozen sections, and MART-1 is surrently the preferred immunostain for this purpose. Other methods of IHC are currently under investigation. Regardless, surgical methods that employ this degree of margin assessment offer superior cure rates compared to standard excision, and should be seriously considered when encountering patients with LM. Total peripheral margin assessment using staged excisions and analysis of permanent sections appears to be a simple and effective alternative to MMS, especially for institutions that prefer examination of permanent sections to frozen sections.

Pathologic examination of the sentinel lymph node in malignant melanoma.

Sentinel lymphadenectomy is gaining increasing popularity in the staging and treatment of patients with melanoma at risk for metastases. As a result, pathologists are encountering these specimens more frequently in their daily practice. The pathologic status of the sentinel lymph node is pivotal to the patient's care because it provides staging information that dictates the need for further therapy, and therefore detailed pathologic assessment is warranted. A standard pathology protocol to handle these nodes has been developed at our institution and involves complete submission of all tissue with routine use of immunohistochemical staining for S-100 protein. By using this protocol, 838 sentinel lymph nodes from 357 patients have been examined, and metastases were found in 16% of patients. Although the metastasis was clearly seen on sections stained with hematoxylin and eosin in 55% of the positive patients, the immunostain showed metastatic disease not appreciable on initial hematoxylin and eosin screening in an additional 28 lymph nodes (45% of node-positive patients). Intraoperative touch preparation cytology may be used as an adjunct technique in sentinel lymph nodes grossly suspicious for metastatic disease. This technique has been performed on 23 sentinel lymph nodes, with no false positives and an overall sensitivity of 62%. The thorough pathologic evaluation of sentinel lymph nodes in patients with malignant melanoma requires complete submission of all tissue, routine use of immunohistochemistry, and touch preparation cytology in selected cases.

Differential expression of thyroid transcription factor 1 in small cell lung carcinoma and Merkel cell tumor.

The distinction between metastatic small cell lung carcinoma (SCLC) and Merkel cell tumor is difficult by routine histology, prompting the search for specific markers that could separate these neoplasms. Thyroid transcription factor 1 (TFF-1) is a homeodomain containing transcription factor expressed in the normal airway epithelium. The expression of TTF-1 has also been shown in adenocarcinomas and small cell carcinomas of the lung. However, the utility of TTF-1 to differentiate between SCLC and Merkel cell tumor has not yet been investigated. In this study, paraffin sections of 36 SCLCs and 21 Merkel cell tumors were analyzed for the presence of immunoreactive TTF-1 and cytokeratin 20 (CK20), a marker previously demonstrated in Merkel cell tumors. Monoclonal TTF-1 and CK20 antibodies were used with a biotin-streptavidin detection system. Immunostaining for TTF-1 was observed in 97% of SCLCs and in no Merkel cell tumors. Immunoreactivity for CK20 was demonstrated in 76% of Merkel cell tumors and 3% of SCLCs. These data indicate that TTF-1 is a sensitive (97%) and specific (100%) marker for SCLCs and can be used to differentiate SCLCs from Merkel cell tumors.

Atypical Spitz nevi/tumors: lack of consensus for diagnosis, discrimination from melanoma, and prediction of outcome.

The biological nature of Spitz nevi/tumors and their diagnostic distinction from, or relationship to, melanoma remain unresolved issues. In this report, a series of 30 melanocytic lesions removed from 28 patients, including atypical Spitz nevi/tumors and metastasizing Spitzoid tumors/melanomas, were evaluated by a panel of dermatopathologists to evaluate interobserver diagnostic concordance and to assess the prognostic power of histological criteria. For inclusion in the study, each lesion had to display some criteria for the Spitz nevus, and in addition one of the following was required: (1) definitive clinical outcome such as metastasis or death of disease, or (2) long-term follow-up if the patient remained disease free. Each lesion was reviewed independently and blinded as to the clinical data by 10 pathologists, who categorized them as (1) typical Spitz nevus/tumor, (2) atypical Spitz nevus/tumor, (3) melanoma, (4) tumor with unknown biological potential, or (5) other melanocytic lesion. There was limited discussion of criteria before the review. Evaluation of 17 Spitzoid lesions yielded no clear consensus as to diagnosis; in only one case did six or more pathologists agree on a single category, regardless of clinical outcome. Notably, however, some lesions that proved fatal were categorized by most observers as either Spitz nevi or atypical Spitz tumors. Conversely, seven or more pathologists scored 13 lesions as melanoma. These results illustrate (1) substantial diagnostic difficulties posed by many Spitz tumors, especially those with atypical features, even among experts, and (2) the lack of objective criteria for their distinction from melanoma and for gauging their malignant potential. Nevertheless, our observations do suggest that a biological relationship exists between the Spitz nevus/tumor and melanoma.

Bleomycin-mediated electrochemotherapy of metastatic melanoma.

BACKGROUND: Electroporation is a new technique that enhances the antitumor effects of chemotherapy by exposing cancerous tissues to pulses of electricity. When used in combination with conventional chemotherapy, the procedure is termed electrochemotherapy (ECT). The electric pulses increase cell membrane permeability and thus intracellular access. Electrochemotherapy has been shown to have potent antitumor activity in a number of in vitro studies, several animal models, and clinical trials with squamous cell carcinomas and basal cell carcinomas. OBJECTIVE: To report the effects of ECT in 5 patients with metastatic malignant melanoma. RESULTS: Twenty-three lesions of metastatic melanoma were treated with intralesional bleomycin sulfate followed by pulses of electricity. Pulses were delivered via caliper or needle electrodes placed around the tumor. Complete responses were observed in 18 tumors (78%) and partial responses were seen in 4 (17%). No responses were seen in lesions treated with either pulses or bleomycin alone. Vital signs were closely monitored during the procedure, and minimal side effects were noted. CONCLUSIONS: This is the first study that documents the antitumor effects of ECT in metastatic melanoma. Although not a cure, it may be an effective alternative to palliative surgery or irradiation in these patients.

The clinical relevance of molecular staging for melanoma.

The presence of metastatic disease in the regional nodal basin is the most important prognostic indicator for patients with malignant melanoma. The metastatic status of the sentinel lymph node (SLN), defined as the first node in the basin to drain a primary tumor, has been shown to represent that of the entire basin. Since routine histologic examination of lymph nodes often underestimates the presence of micrometastatic disease, a more sensitive assay for detecting tumor cells is needed. We have previously shown that a molecular assay based on the reverse transcriptase polymerase chain reaction (RT-PCR) was able to define a population of patients at higher risk for both recurrence and death, compared with routine H&E histology. Recently, we have compared "molecular staging" of patients by RT-PCR with conventional S-100 immunohistochemistry (IHC) staining of the SLNs. In these studies, SLN specimens were bivaled, and half of each specimen was examined by routine histology, including both H&E and S-100 IHC. The other half of each specimen was analyzed by a nested RT-PCR assay. H&E histology alone detected metastatic disease in 36 of 233 (16%) patients tested. Serial sectioning and IHC detected micrometastatic disease in another 16 patients, thus increasing the proportion of patients with nodal disease to 22%. RT-PCR detected micrometastatic disease in 114 of 181 patients who were negative by conventional methods, further increasing the proportion of patients with evidence of nodal disease to 70% overall. The clinical significance of these findings is still uncertain. The value of additional therapy (including elective lymph node dissection and interferon therapy) for patients who are positive only by the molecular method is currently being investigated by the national multi-center Sunbelt Melanoma Trial.

Pathologic examination of the sentinel lymph node in melanoma.

The techniques of lymphatic mapping and sentinel lymph node biopsy are effective methods of accurately staging melanoma patients and identifying those who may benefit from further surgery or adjuvant chemotherapy. This article describes a standard pathology protocol for examination of sentinel lymph nodes in melanoma. Details of this standardized lymph node examination, institutional results using the protocol, and a literature review concerning lymph node findings in malignant melanoma are included.

Cost analysis of sentinel lymph node biopsy as an alternative to elective lymph node dissection in patients with malignant melanoma.

In the current era of managed care and cost containment, physicians and administrators are placed in the predicament of increasing quality of care while decreasing costs. The purpose of this article is to offer a cost analysis, while also demonstrating what patients, providers, payers, employers, and industry may stand to gain from establishing sentinel lymph node biopsy as a standard care in certain groups of patients.

Cancer of the skin in the older patient.

This article focuses on the common precancers and skin cancers in the older patient. The hazards of ultraviolet radiation are explained briefly in relation to photoaging and the development of skin cancer. The etiology, clinical appearance, histopathologic diagnosis, treatment, and follow-up for each type of cancer are reviewed thoroughly. It is hoped that early recognition and treatment by geriatric physicians will have a positive impact on the reduction of the morbidity and mortality associated with these cancers in the elderly.

Lymphatic mapping and sentinel lymph node biopsy in patients with melanoma of the lower extremity.

Lymphatic mapping and sentinel lymph node biopsy is a new technique used in the surgical treatment of patients with malignant melanoma. The purpose of this study was to evaluate the results of this approach for patients with melanoma of the lower extremity. Between May of 1994 and June of 1997 at the H. Lee Moffitt Cancer Center and Research Institute, 85 consecutive patients with clinical stage I and II melanoma of the lower extremity underwent lymphatic mapping and sentinel lymph node biopsy. These nodes were identified in all 85 patients by intraoperative lymphatic mapping with both radiolymphoscintigraphy and a vital blue dye injection. Eleven patients (12.9 percent) had histologically positive sentinel lymph nodes, and 10 patients underwent inguinal complete lymph node dissections. All 10 patients had no further histologically positive lymph nodes confirmed by subsequent complete dissection. Among 74 patients with histologically negative sentinel lymph nodes, only 2 patients (2.7 percent) developed inguinal nodal metastases during a mean follow-up period of 21.8 months (range, 13.5 to 58.3 months). The sensitivity of lymphatic mapping and sentinel lymph node biopsy in this series was 100 percent and the specificity was 97.3 percent. Therefore, we conclude that the use of lymphatic mapping and sentinel lymph node biopsy can accurately stage patients with melanoma of the lower extremity and provide a rational surgical approach for these patients.

Rosaceous lymphedema: a rare variant of a common disorder.

Rosaceous lymphedema is considered to be a rare and disfiguring variant of acne rosacea. Cases remain difficult to treat and can challenge afflicted patients both cosmetically and psychologically. We describe an unusual presentation of rosaceous lymphedema and review the differential diagnosis of persistent facial edema.

Morsicatio buccarum et labiorum (excessive cheek and lip biting).

In some individuals habitual cheek and lip biting becomes a fixed neurosis. Pieces of oral mucosa are actually torn free from the surface, producing a distinctive clinical appearance termed morsicatio buccarum et labiorum. Sometimes it may be confused with other dermatological disorders involving the oral mucosa, and can lead to misdiagnosis. Most patients with this condition are unaware of their habit and will not aid in the diagnosis. We suggest that the histopathological features of this condition are distinctive, if not pathognomonic, and that an accurate diagnosis should be rendered if a biopsy sample is taken. Two cases are reported herein that were originally misdiagnosed as pemphigus, one of which resulted in complications of improper oral corticosteroid use.

Pathologic examination of the sentinel lymph node.

One of the most important prognostic indicators in patients with malignant melanoma is lymph node status. While the five-year survival of stage I and II patients (without clinical adenopathy) is approximately 80 percent, this drops to 36-50 percent in patients with clinical or microscopic lymph node involvement. Other factors within lymph node specimens which affect disease-free and overall survival are the number of positive nodes (1 vs. 1-3 vs. 4 or greater) and the presence of extracapsular extension. Recently, the technique of sentinel lymphadenectomy has been developed to facilitate detection of metastatic disease in regional lymph nodes. Successful completion of this procedure requires a specialized but multidisciplinary approach, utilizing the surgeon, oncologist, nuclear radiologist, and pathologist. The pathologist's role is pivotal in this process, because identification of melanoma metastasis in the sentinel lymph node(s) is not only an important prognostic indicator but also dictates whether the patient will receive further surgery and adjuvant chemotherapy. Therefore, the goal of the pathologist in examining the sentinel lymph node is to maximize identification of nodal metastases of malignant melanoma. This is accomplished by following a standard protocol which fully utilizes all tissue submitted in concert with commonly available immunohistochemical techniques.

Treatment of perifolliculitis capitis abscedens et suffodiens with the carbon dioxide laser.

We describe the successful use of the carbon dioxide (CO2) laser for localized surgical therapy in a patient with perifolliculitis capitis abscedens et suffodiens that was refractory to conservative treatment.

Merkel cell carcinoma. Diagnosis and treatment.

BACKGROUND: Merkel cell carcinoma is an uncommon malignancy of the skin that often portends a poor prognosis. Since its first description by Toker in 1972, a plethora of case reports and articles regarding the etiopathogenesis and treatment have been published spanning multiple medical and surgical disciplines. Much confusion still exists regarding the diagnosis and treatment of this ominous tumor. OBJECT: Through extensive review of the medical, surgical, and pathological literature, to collate the observations of multiple investigators and summarize these findings. METHODS: Articles from journals of multiple subspecialties were carefully reviewed with particular emphasis placed on epidemiology, prognosis, histology, immunohistochemistry, electron microscopy, tumor origin, treatment, and work-up of Merkel cell carcinoma. RESULTS: Merkel cell carcinoma is an aggressive malignant neoplasm. Local recurrence develops in 26-44% of patients despite therapy. Up to three-fourths of patients eventually develop regional nodal metastases with distant metastases occurring in one-third of all patients. Reported overall 5-year survival rates range from 30% to 64%. CONCLUSION: Treatment recommendations unfortunately are based more on anecdotal than scientific data because of the rarity of the tumor and its recognized high risk. Most authors recommend wide local excision of the primary lesion and regional lymph node resection if lymph nodes are palpable followed by x-irradiation of both the postsurgical bed and lymph node basin. The role of elective lymph node resection in the absence of clinically positive nodes remains controversial.

A generalized cutaneous reaction induced by granulocyte colony-stimulating factor.

BACKGROUND: The increasing use of recombinant forms of granulocyte and granulocyte-macrophage colony-stimulating factors (GCSF and GMCSF) for neutropenic conditions has resulted in reports of a variety of cutaneous reactions. OBJECTIVE: We studied the clinical and histologic findings in three patients who underwent bone marrow transplantation and subsequently had a cutaneous eruption associated with the use of GCSF. METHODS: Biopsy specimens taken at the height of the eruption were studied histologically and immunohistochemically. RESULTS: The patients had indurated, well-demarcated, occasionally annular, erythematous desquamation after withdrawal of the medication. Distinctive histologic features consisted of mild epidermal spongiosis overlying a dermal infiltrate of enlarged, plump macrophages. Increased expression of the vascular adhesion molecules ELAM-1 and VCAM-1, as well as the histologic keratinocyte-produced ICAM-1, was noted. CONCLUSION: the clinical and histological findings of the cutaneous reaction to GCSF are characteristic and allow its distinction from other eruptions that occur in bone marrow transplant recipients.

Eccrine angiomatous hamartoma.

BACKGROUND: Eccrine angiomatous hamartoma (EAH) is a rare benign lesion that mimics a capillary ("strawberry") hemangioma (CH) in appearance. EAH slowly grows and becomes symptomatic whereas CH typically regresses over time. OBJECTIVE: To increase awareness of this rare hamartoma and emphasize the need for histopathologic evaluation of similar appearing lesions and thus prompt excision versus observation. METHODS: Literature review and report of an illustrative case. RESULTS: Histopathologic confirmation of EAH in a lesion clinically indistinguishable from CH and successful surgical extirpation. CONCLUSION: EAH is a rare hamartomatous neoplasma clinically similar to CH in appearance. Histopathologic examination of suspected lesions is recommended for delineation as CH generally involutes spontaneously whereas EAH may require surgical excision due to pain and hyperhidrosis.

Fibromucinous T-cell lymphoma: a new clinicopathologic variant of mycosis fungoides?

We report a case of mycosis fungoides associated with extensive dermal fibrosis and mucin deposition. The patient developed indurated plaques with diffuse tightening of the skin reminiscent of the sclerosing disorder scleromyxedema, which was later associated with nodules and lymphadenopathy. Skin biopsies showed diffusely thickened collagen bundles in the dermis and mucin deposition with a dense infiltrate of atypical lymphocytes with an immunophenotypic pattern indicative of mycosis fungoides. In our opinion, these clinical and histopathologic features are unusual for mycosis fungoides and can be construed as a distinct fibromucinous variant. Alternatively, this may represent a fibrosing reaction pattern similar to that described with systemic T- and B-cell lymphomas or a variety of inflammatory disorders.

Alkaptonuria and ochronosis: case report and review.

Alkaptonuria is a rare genetic disorder in which the enzyme homogentisic acid oxidase is deficient, resulting in the accumulation of homogentisic acid in various bodily tissues. This is a multisystem disorder with a characteristic blue-black discoloration of the skin and cartilage, which is termed ochronosis. Herein we report a profound case of ochronosis secondary to alkaptonuria. Furthermore, we review the clinical manifestations of alkaptonuria and discuss the spectrum of ochronosis, both endogenous and exogenous.