Potential utility of adjunctive histopathologic evaluation of some tumors treated by Mohs micrographic surgery.

BACKGROUND: Mohs micrographic surgery is a highly effective, tissue-conserving method for removing certain cutaneous neoplasms. Horizontal Mohs tissue sectioning permits complete histologic evaluation of the true surgical margin, but does not aim to evaluate the overall morphology of the tumor. Mohs surgery is designed primarily to answer the question "Is it all out?" as opposed to "What is it?" A preoperative biopsy is relied on, in most cases, to provide an accurate diagnosis. The histology from this biopsy might be the only view of the tumor if the first Mohs stage is clear. However, histopathologic review of small biopsies may sometimes give incomplete information about the entirety of the tumor. OBJECTIVE: To illustrate the potential utility of adjunctive histopathologic examination of some tumors treated by Mohs surgery. METHODS: We present four cases to illustrate situations where pre-Mohs biopsy provided incomplete information. The limitations of these biopsies was clarified after the tumor was visualized on a positive first Mohs layer and/or when the tissue was subsequently sectioned vertically. RESULTS: Cases of tumors where preoperative biopsies gave incomplete information are presented: sebaceous carcinoma versus basal cell carcinoma (BCC), invasive versus in situ squamous cell carcinoma (SCC), and SCC versus keratoacanthoma. CONCLUSION: The Mohs technique allows histologic examination of the complete surgical margin around cutaneous neoplasms, optimizing tissue sparing and resulting in superior cure rates. However, in rare cases additional evaluation of the tissue by vertical sectioning can provide important adjunctive histopathologic information that can effect ultimate patient management.

Combined sentinel lymphadenectomy and mohs micrographic surgery for high-risk cutaneous squamous cell carcinoma.

BACKGROUND: There are subgroups of cutaneous squamous cell carcinoma (SCC) that have a higher risk for both regional and distant metastasis. When cutaneous SCC does metastasize, it typically spreads first to local nodal groups. Sentinel lymph node (SLN) localization has been successfully used to evaluate nodal metastasis in breast carcinoma, melanoma, and other select tumors. It may also be useful in certain high-risk cutaneous SCCs. Currently, Mohs micrographic surgery is the treatment of choice for these tumors. METHODS: A patient presented with a high-risk recurrent SCC on the forehead. The regional nodal groups were clinically negative and radiographically negative by computed tomographic scan. Sentinel lymphadenectomy was performed by means of technetium 99m-radiolabeled sulfur colloid. The main tumor was resected with Mohs micrographic surgery. RESULTS: A left preauricular SLN was localized by lymphoscintigraphy. The SLN was located intraoperatively by means of a gamma probe and excised. Subsequent pathologic evaluation of the SLN was negative for evidence of metastatic SCC by light microscopy with hematoxylin and eosin, and with immunohistochemical stains for cytokeratins AE1 and AE3. The day after SLN excision, the tumor was removed via Mohs micrographic surgery with clear surgical margins after a total of 8 stages. Aggressive subclinical spread by both subcutaneous "skating" and perineural invasion was noted. CONCLUSION: The combination of Mohs micrographic surgery and sentinel lymphadenectomy is feasible and has theoretical utility in the management of a subset of cutaneous SCCs at high risk for metastasis. The ability of sentinel lymphadenectomy to identify regionally metastatic cutaneous SCC as well as the additive benefit of SLN and Mohs micrographic extirpation in the treatment of high-risk cutaneous SCC remain to be further clarified.

Enhancement by cyclic AMP of antibody-induced suppression of the fourth component of complement.

Our laboratory has shown that short-term treatment in vivo or in vitro with monospecific antibody to individual complement components can have long-term effects on the production of those components. In vitro studies have focused on the fourth component of complement (C4) in a guinea pig model. Uniform splenic fragments have been used to mimic the in vivo microenvironment of the C4-producing macrophages. A 4-day exposure to anti-C4 antibody led to a reduction of secreted C4 for 1 to 2 wk and a reduction of intracellular C4 that persisted even longer. In an attempt to understand how short-term exposure to antibody can specifically and permanently disrupt the C4-producing cell, we have determined whether C4 suppression could be enhanced by components that modulate cellular functions through their role as secondary intracellular messengers. We found that compounds which elevated cellular levels of cAMP by any of three mechanisms all enhanced antibody-induced suppression of C4.

Antibody-induced suppression and postsuppression stimulation of complement in vitro. II. Intracellular and extracellular changes in C4 during long-term C4 suppression in guinea pig splenic fragments.

Suppression of the synthesis of the fourth component of complement in vitro was originally accomplished by exposing cultured guinea pig peritoneal cells to anti-C4 alloantisera. When guinea pig splenic fragments were used instead of peritoneal cells, equivalent antibody treatment produced C4 suppression of significantly longer duration, lasting weeks instead of days after removal of antibody. As with peritoneal cell monolayers, antibody treatment induced specific suppression of C4 followed by nonspecific stimulation of C4 and other proteins such as C2. Although IgG2 is more readily sequestered by splenic tissue, both IgG1 and IgG2 antibodies were effective in inducing and maintaining suppression. Experiments with radiolabeled antibody demonstrated that a small amount (less than 5%) of the original dose of antibody was retained by the splenic fragments. Because there was no continuous slow release of that antibody, long-term suppression of C4 cannot be explained as a fluid-phase neutralization reaction. Because antibody treatment might induce production of aberrant C4 molecules with no functional activity, C4 antigens was also studied. Tissue culture supernatants were assayed by using an ELISA for C4. In none of these experiments was extracellular C4 antigen detectable immediately after antibody treatment. Extracellular and intracellular C4 were immunoprecipitated from biosynthetically labeled tissue cultures and analyzed by SDS-PAGE. Antibody treatment suppressed intracellular C4 as well as extracellular C4. Although extracellular C4 levels of antibody-treated cultures eventually returned to levels comparable to untreated cultures, intracellular C4 levels of treated fragments remained lower than controls for the full period of observation (22 days). Therefore, a short (4-day) exposure to anti-C4 antibody induced long-term effects that profoundly altered regulation of C4 synthesis and secretion by cultured splenic macrophages.