Showing papers by "Alexander J. Lazar published in 2008"
TL;DR: Patients harboring CTNNB1 (45F) mutations are at particular risk for recurrence and therefore may especially benefit from adjuvant therapeutic approaches.
Abstract: Desmoid fibromatosis is a rare, nonmetastatic neoplasm marked by local invasiveness and relentless recurrence. Molecular determinants of desmoid recurrence remain obscure. β-Catenin deregulation has been commonly identified in sporadic desmoids although the incidence of CTNNB1 (the gene encoding β-catenin) mutations is uncertain. Consequently, we evaluated the prevalence of CTNNB1 mutations in a large cohort of sporadic desmoids and examined whether mutation type was relevant to desmoid outcome. Desmoid specimens (195 tumors from 160 patients, 1985 to 2005) and control dermal scars were assembled into a clinical data-linked tissue microarray. CTNNB1 genotyping was performed on a 138-sporadic desmoid subset. Immunohistochemical scoring was performed per standard criteria and data were analyzed using Kaplan-Meier and other indicated methods. CTNNB1 mutations were observed in 117 of 138 (85%) of desmoids. Three discrete mutations in two codons of CTNNB1 exon 3 were identified: 41A (59%), 45F (33%), and 45P (8%, excluded from further analysis because of rarity). Five-year recurrence-free survival was significantly poorer in 45F-mutated desmoids (23%, P < 0.0001) versus either 41A (57%) or nonmutated tumors (65%). Nuclear β-catenin expression was observed in 98% of specimens and intensity was inversely correlated with incidence of desmoid recurrence (P < 0.01). In conclusion, CTNNB1 mutations are highly common in desmoid tumors. Furthermore, patients harboring CTNNB1 (45F) mutations are at particular risk for recurrence and therefore may especially benefit from adjuvant therapeutic approaches.
395 citations
TL;DR: The first report of AKT mutations in melanoma, and the initial identification of an AKT3 mutation in any human cancer lineage, are reported and the first known human cell lines with naturally occurring AKT E17K mutations are identified.
Abstract: Recently, a rare activating mutation of AKT1 (E17K) has been reported in breast, ovarian, and colorectal cancers. However, analogous activating mutations in AKT2 or AKT3 have not been identified in any cancer lineage. To determine the prevalence of AKT E17K mutations in melanoma, the most aggressive form of skin cancer, we analysed 137 human melanoma specimens and 65 human melanoma cell lines for the previously described activating mutation of AKT1, and for analogous mutations in AKT2 and AKT3. We identified a single AKT1 E17K mutation. Remarkably, a previously unidentified AKT3 E17K mutation was detected in two melanomas (from one patient) as well as two cell lines. The AKT3 E17K mutation results in activation of AKT when expressed in human melanoma cells. This represents the first report of AKT mutations in melanoma, and the initial identification of an AKT3 mutation in any human cancer lineage. We have also identified the first known human cell lines with naturally occurring AKT E17K mutations.
258 citations
TL;DR: It is found COL1A1-PDGFB rearrangements appear more prevalent in DFSP than previously reported and may be particularly helpful in the differential diagnosis of atypical, fibrosarcomatous, and metastatic DFSP.
186 citations
TL;DR: Insight into the molecular basis of sarcoma inception, proliferation, and dissemination hopefully will lead to more effective therapies, and increased knowledge of the oncogenic mechanisms underlying sarcomagenesis is being generated.
145 citations
TL;DR: Tumor size and grade in the AJCC STS staging system need revision; moreover, primary site, histologic subtype, margin status, and recurrence offer additional relevant prognostic insight.
Abstract: Data suggest that the current American Joint Committee on Cancer (AJCC) soft tissue sarcoma (STS) staging criteria merit further evaluation. We sought to identify and validate factors as enhanced descriptors of STS clinical behavior. Prospectively accrued data were analyzed for 1,091 AJCC stage I to III primary STS patients who had complete macroscopic resection at our institution from 1996 to 2007. Study factors were examined by univariable and multivariable analyses to identify independent prognostic factors for disease related mortality and overall survival (OS). In contrast to the current AJCC STS staging system, which stratifies size into T1 (≤5 cm) and T2 (>5 cm) groups, we demonstrated three distinct cohorts (P 15 cm; OS 52%). A two-category system of histologic grade was demonstrably as informative as the current four histologic grade AJCC system. A multivariable Cox proportional hazard model identified tumor size (5 to 15 cm vs. ≤5 cm, P = 0.03; or >15 cm vs. ≤5 cm; P < 0.0001), nonextremity primary site (P = 0.0016), disease of high histologic grade (P = 0.001), specific histology (P = 0.001), and margin positivity (P < 0.0001) as statistically significant adverse independent prognostic factors. Recurrence during follow-up was the most significant risk factor for STS-specific mortality (P < 0.0001). Tumor size and grade in the AJCC STS staging system need revision; moreover, primary site, histologic subtype, margin status, and recurrence offer additional relevant prognostic insight. Incorporation of these factors may enhance the AJCC staging system, thereby further facilitating individualized therapeutic strategies for STS patients.
138 citations
TL;DR: It is suggested that the prognosis is not always poor and that grading criteria devised for breast carcinoma may have utility in this group of malignancies, and steroid receptor expression should be investigated in these tumors.
Abstract: Primary cutaneous apocrine carcinoma is a rare malignancy. This study of 24 examples suggests that the prognosis is not always poor and that grading criteria devised for breast carcinoma may have utility in this group of malignancies. Furthermore, steroid receptor expression should be investigated in these tumors, particularly if a tumor is unlikely to be controlled by surgery alone.
130 citations
TL;DR: A 79-year-old man presented to his primary care physician with a 2-month history of pruritus ani and a pigmented nodular lesion was discovered in the posterior rectum and was diagnosed with Stage IV M1b metastatic anal mucosal melanoma.
Abstract: Anal mucosal melanoma is a disorder with limited treatment options and is associated with a poor prognosis. The authors describe the case of a 79-year-old man who was diagnosed with stage IV anal mucosal melanoma expressing the KIT Val560Asp mutation, and was treated with surgery, radiotherapy, and a combination of sorafenib and temozolomide therapy. The authors discuss the potential therapeutic use of sorafenib in anal mucosal melanoma patients with specific mutations such as the KIT Val560Asp mutation. Background A 79-year-old man presented to his primary care physician with a 2-month history of pruritus ani and a pigmented nodular lesion was discovered in the posterior rectum. The patient had no other symptoms, or any family history of malignancy. Investigations Physical examination; excisional biopsy; CT scan of the chest, abdomen and pelvis; lung biopsy; blood tests; tumor immunohistochemistry for KIT, vascular endothelial growth factor platelet-derived growth factor receptor α and β, and mismatch-repair proteins MLH1, MSH2, and MSH6; and KIT and BRAF tumor genotyping. Diagnosis Stage IV M1b metastatic anal mucosal melanoma. Management Wide local excision with mucosal advancement of the rectal wall, external-beam radiation, and sorafenib–temozolomide therapy.
108 citations
TL;DR: In an era of molecularly targeted therapeutics there is a real need to better grasp the molecular mechanisms behind desmoid tumorigenesis and progression, to result in the development of patient and tumor tailored therapies and assist in the control and eradication of this disease.
Abstract: Desmoid tumors are monoclonal proliferations that fall within a broad histologic spectrum of fibrous mesenchymal tumors that ranges from benign proliferations of scar tissue to high-grade fibrosarcomas. These low-grade tumors are extremely infiltrative locally, but lack the ability to metastasize systemically. While they are only rarely a direct cause of mortality, using current therapeutic modalities, these tumors have a high rate of local recurrence that can result in significant treatment related morbidity. Sporadic desmoids are usually associated with somatic mutations in codons 41 or 45 of exon 3 of beta-catenin (CTNNB1). Desmoid tumors occurring in the background of familial adenomatous polyposis (FAP) usually contain inactivating germline mutations in the adenomatous polyposis coli (APC) gene. CTNNB1 and APC are part of the Wnt signaling pathway and mutations in either gene result in stabilization of the beta-catenin protein and allow nuclear translocation and binding of beta-catenin to the T-cell factor/lymphoid enhancer factor (TCF/Lef) family of transcription factors, resulting in activation of target genes which may underlie desmoid tumor biology and clinical behavior. In an era of molecularly targeted therapeutics there is a real need to better grasp the molecular mechanisms behind desmoid tumorigenesis and progression. This knowledge will eventually result in the development of patient and tumor tailored therapies and assist in the control and eradication of this disease.
100 citations
TL;DR: Cutaneous sebaceous neoplasia has tendencies toward certain tumor types and anatomic distribution based on MMR status analogous to that seen in colonic carcinomas and other tumors, and may be helpful indicators for further workup for the Muir-Torre syndrome.
Abstract: Cutaneous sebaceous neoplasia is known to exhibit a high degree of DNA mismatch repair (MMR) deficiency leading to microsatellite instability and these tumors can be markers of the Muir-Torre syndrome and internal malignancy. Other tumors, such as colonic carcinoma, show tendencies toward particular histologic features and sites of involvement correlating with MMR deficiency. There are few comprehensive studies of unselected cutaneous sebaceous neoplasms. To address this gap in knowledge, we examined 94 sebaceous neoplasms from 92 patients and 17 sebaceous hyperplasia controls using immunohistochemistry for MLH1, MSH2, and MSH6. Our results indicate that MMR deficiency is significantly associated with anatomic location (more frequently in the trunk and extremities as compared with head and neck), tumor type (more often in adenoma compared with carcinoma within the head and neck region), and architecture (keratoacanthomalike). No correlation between cystic change and MMR deficiency was noted. Cutaneous sebaceous neoplasia has tendencies toward certain tumor types and anatomic distribution based on MMR status analogous to that seen in colonic carcinomas and other tumors. These may be helpful indicators for further workup for the Muir-Torre syndrome.
96 citations
TL;DR: A new paradigm of classification, integrating the standard clinical and pathological criteria with molecular aberrations, may permit personalized prognosis and treatment in GISTs.
Abstract: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm in the gastrointestinal tract and is associated with mutations of the KIT or PDGFRA gene. In addition, other genetic events are believed to be involved in GIST tumorigenesis. Cytogenetic aberrations associated with these tumors thus far described include loss of 1p, 13q, 14q, or 15q, loss of heterozygosity of 22q, numeric chromosomal imbalances, and nuclear/mitochondrial microsatellite instability. Molecular genetic aberrations include loss of heterozygosity of p16(INK4A) and p14(ARF), methylation of p15(INK4B), homozygous loss of the Hox11L1 gene, and amplification of C-MYC, MDM2, EGFR1, and CCND1. GISTs in patients with neurofibromatosis type 1 appear to lack the KIT and PDGFRA mutations characteristic of GISTs and may have a different pathogenetic mechanism. Gene mutations of KIT or PDGFRA are critical in GISTs, because the aberrant versions not only are correlated with the specific cell morphology, histologic phenotype, metastasis, and prognosis, but also are the targets of therapy with imatinib and other agents. Furthermore, specific mutations in KIT and PDGFR appear to lead to differential drug sensitivity and may in the future guide selection of tyrosine kinase inhibitors. Activation of the receptor tyrosine kinases involves a signal transduction pathway whose components (mitogen-activated protein kinase, AKT, phosphoinositide 3-kinase, mammalian target of rapamycin, and RAS) are also possible targets of inhibition. A new paradigm of classification, integrating the standard clinical and pathological criteria with molecular aberrations, may permit personalized prognosis and treatment.
81 citations
TL;DR: Germ‐line deletion of KIT codon 579 in GIST is associated with clinical benefit from imatinib, limited utility of mitoses to predict malignant potential, and a novel homozygous deletion of this codon in one individual.
Abstract: Germ-line mutations in the KIT receptor tyrosine kinase gene have been described in families with a propensity to develop gastrointestinal stromal tumor (GIST) There is limited information from large kindreds regarding median age at diagnosis, detailed histopathology, clinical effects of imatinib therapy and chromosomal abnormalities of the KIT gene We identified a large kindred with GIST Each family member was interviewed and appropriate medical records and radiographic imaging were obtained Archival tumor tissue was obtained to confirm diagnosis, extract genomic DNA and perform fluorescent in situ hybridization cytogenetics of the KIT gene Fifteen of 79 individuals with GIST were identified in this kindred There were 8 males, the mean age at diagnosis was 539 (range 45-71) years Histopathology revealed microscopic proliferation and nodularity in the myenteric plexus, spindled morphology, diffuse Kit but variable CD34 staining and low mitotic rates in the setting of metastatic disease A deletion of codon 579 in exon 11 of the KIT gene was identified in tumor and normal tissue of this family Mutation and cytogenetic analysis revealed homozygous loss of the wild-type KIT sequence in tumor from one individual Four of 4 individuals treated with imatinib are alive and without progression while 9 of 11 individuals not treated with imatinib are deceased This study describes a kindred with a propensity to develop GIST in an autosomal dominant pattern Germ-line deletion of KIT codon 579 in GIST is associated with clinical benefit from imatinib, limited utility of mitoses to predict malignant potential, and a novel homozygous deletion of this codon in one individual
TL;DR: Tumors without a rearrangement of the EWSR1 gene should be descriptively characterized as uterine tumors with neuroectodermal differentiation or alternatively central type PNETs rather than PNET, not otherwise specified to avoid confusion with peripheral PNET.
Abstract: Uterine tumors with neuroectodermal differentiation, frequently referred to as primitive neuroectodermal tumors (PNETs), are uncommon The clinicopathologic features of 17 such cases reviewed at the MD Anderson Cancer Center (MDACC) are presented along with a review of the literature All of the pathology material was reviewed at MDACC, and in all cases, immunohistochemistry contributed to the diagnosis In 12 cases, in situ hybridization techniques were used to determine whether a rearrangement of the EWSR1 gene, required for a diagnosis of peripheral PNET, was present Clinical information was obtained from a patient chart review Ages ranged from 31 to 81 years (median 58) Clinical presentations included vaginal bleeding (9), back pain (1), presumed fibroids (2), pelvic mass (1), incidental finding at hysterectomy (1), and unknown (3) Twelve patients had surgery or imaging to determine stage: I (2), II (0), III (6), and IV (4) Five patients had biopsy only Ten tumors had only neuroectodermal components In 7 tumors, the neuroectodermal component was admixed with an additional component including unclassified sarcoma (2 cases), rhabdomyosarcoma, endometrioid carcinoma, adenosarcoma and malignant mixed Mullerian tumor (2 cases) Follow-up, available for 13 patients, ranged from 2 to 41 months with 7 patients dead of disease 2 to 26 months after diagnosis Six patients are alive with no evidence of disease after follow-up ranging from 6 to 41 months Four patients were lost to follow-up Results for the most commonly used immunohistochemistry studies include cytokeratin, 13/15 tumors negative (2 focally positive); synaptophysin, 15/16 tumors positive; neurofilament, 10/11 tumors positive; and CD99, 7/9 tumors positive (2 tumors had nonspecific cytoplasmic staining) None of the 12 tumors tested had a detectable rearrangement in the EWSR1 gene Uterine tumors with neuroectodermal differentiation, similar to more common endometrial malignancies, tend to occur in postmenopausal women and frequently present with vaginal bleeding An immunohistochemistry panel including cytokeratin, neurofilament, synaptophysin, and CD99 can highlight neuroectodermal differentiation and identify tumors for which molecular testing should be considered Tumors without a rearrangement of the EWSR1 gene should be descriptively characterized as uterine tumors with neuroectodermal differentiation or alternatively central type PNETs rather than PNET, not otherwise specified to avoid confusion with peripheral PNET
TL;DR: MK enhances STS tumor growth; the results support further investigation of MK and its receptors as therapeutic targets for human STS.
Abstract: Purpose: New therapeutic targets for soft-tissue sarcoma (STS) treatment are critically needed. Midkine (MK), a multifunctional cytokine, is expressed during midgestation but is highly restricted in normal adult tissues. Renewed MK expression was shown in several malignancies where protumorigenic properties were described. We evaluated the expression and function of MK in STS. Experimental Design: Immunohistochemistry, reverse transcription-PCR, and Western blotting (WB) evaluated MK expression in human STS tissues and cell lines. WB and flow cytometry analyzed MK receptor expression. Cell growth assays evaluated the effect of MK on STS cell growth, and WB assessed MK downstream signaling. MK knock-in and knockout experiments further evaluated MK function. The growth of parental versus MK-transfected human fibrosarcoma cells was studied in vivo . Results: MK was found to be overexpressed in a variety of human STS histologies. Using a rhabdomyosarcoma (RMS) tissue microarray, cytoplasmic and nuclear MK was identified; nuclear MK expression was significantly increased in metastases. Similarly, several STS cell lines expressed and secreted MK; RMS cells exhibited nuclear MK. STS cells also expressed the MK receptors protein tyrosine phosphatase ζ and lipoprotein receptor-related protein. MK significantly enhanced STS cell growth potentially via the Src and extracellular signal-regulated kinase pathways. STS cells stably transfected with MK exhibited increased growth in vitro and in vivo . MK-expressing human STS xenografts showed increased tumor-associated vasculature. Furthermore, MK knockdown resulted in decreased STS cell growth, especially in RMS cells. Conclusion: MK enhances STS tumor growth; our results support further investigation of MK and its receptors as therapeutic targets for human STS.
TL;DR: EGFR blockade combined with conventional chemotherapy results in anti-human STS activity in vitro and in vivo, suggesting the possibility that combining these synergistic treatments will improve anti-STS therapy.
Abstract: Purpose: The epidermal growth factor receptor (EGFR) is highly expressed in many human soft tissue sarcomas (STS). However, EGFR blockade has not apparently been used for human STS therapy; therefore, we examined the in vitro and in vivo effects and the underlying mechanisms before considering EGFR blockade as a therapy for STS patients. Experimental Design: Human STS tissues and cell lines were used to study EGFR expression and activation. Western blot analysis was used to evaluate effects of EGFR activation on downstream signaling. Cell culture assays were used to assess the effect of EGF stimulation as well as EGFR blockade (using an EGFR tyrosine kinase inhibitor, Iressa; AstraZeneca) on STS cell growth, apoptosis, and chemosensitivity. An in vivo study (HT1080 human fibrosarcoma cell line in nude/nude mice: Iressa, doxorubicin, Iressa + doxorubicin, vehicle) was used to examine tumor growth; pEGFR, proliferating cell nuclear antigen, and terminal deoxyribonucleotide transferase–mediated nick-end labeling staining helped assess the effect of therapy in vivo on STS EGFR activation, proliferation, and apoptosis. Results: EGFR was expressed and activated in STS cell lines and tumors, probably due to ligand binding rather than EGFR mutation. Stimulation caused activation of AKT and mitogen-activated protein kinase pathways. EGFR blockade inhibited these effects and also caused increased apoptosis, a p53-independent G 0 -G 1 cell cycle arrest, and decreased cyclin D1 expression. In vivo , Iressa + doxorubicin had markedly synergistic anti-STS effects. Conclusion: EGFR blockade combined with conventional chemotherapy results in anti-human STS activity in vitro and in vivo , suggesting the possibility that combining these synergistic treatments will improve anti-STS therapy.
TL;DR: It is proposed that the ratio of nuclear to non-nuclear HMB45 staining may be useful for diagnostic challenges in melanocytic lesions.
TL;DR: Compared the expression of actin and actin-related cytoskeletal proteins in relatively less aggressive basal cell carcinoma (nodular), aggressive basal Cell Carcinoma (infiltrative/morpheaform), and metastatic basalcell carcinoma, the results suggest that increased actin may contribute to local invasiveness, but it is lost in the metastatic phenotype.
TL;DR: Vandetanib has antitumor effects against human STS subtypes in vitro and in vivo, where it also affects the tumor-associated microenvironment, and clinical trials evaluating vandenib, perhaps with low-dose chemotherapy, seem warranted.
Abstract: Purpose: Soft tissue sarcoma (STS) is a rare heterogeneous malignancy. Overall survival has been stagnant for decades, primarily because systemic therapies are ineffective versus metastases, the leading cause of STS lethality. Consequently, we examined whether tyrosine kinase receptors active in STS growth signaling might be blockable and whether multireceptor blockade might synergize with low-dose STS chemotherapy by therapeutically affecting STS cells and their associated microenvironment. Experimental Design: Vandetanib (AstraZenca), a tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 and epidermal growth factor receptor, was evaluated alone and with chemotherapy in vitro and in vivo in three human STS nude mouse xenograft models of different STS locations (muscle, uterus, lung), stages (primary, metastatic), and subtypes (leiomyosarcoma, fibrosarcoma, uterine sarcoma: luciferase-expressing MES-SA human uterine sarcoma cells surgically implanted into uterine muscularis with bioluminescence tumor growth assessment; developed by us). Results: In vitro , human STS cells were sensitive to vandetanib. Vandetanib alone and with chemotherapy statistically significantly inhibited leiomyosarcoma local growth and fibrosarcoma lung metastasis. Direct injection of MES-SA into nude mice uterine muscularis resulted in high tumor take (88%), whereas s.c. injection resulted in no growth, suggesting microenvironmental tumor growth modulation. Vandetanib alone and with chemotherapy statistically significantly inhibited uterine sarcoma growth. In all models, vandetanib induced increased apoptosis, decreased tumor cell proliferation, and decreased angiogenesis. Conclusions: Vandetanib has antitumor effects against human STS subtypes in vitro and in vivo , where it also affects the tumor-associated microenvironment. Given the urgent need for better systemic approaches to STS, clinical trials evaluating vandetanib, perhaps with low-dose chemotherapy, seem warranted.
TL;DR: Fluorescence in situ hybridization is useful to support the diagnosis of extraskeletal myxoids chondrosarcomas and may help to differentiate it from mimics such as other myxoid sarcomas, particularly in limited biopsies.
TL;DR: Key diagnostic features as well as potential pitfalls are highlighted in reader-friendly tables, facilitating quick reference in a busy diagnostic pathology practice.
Abstract: The authors, both renowned experts in surgical pathology of tumors, expansively discuss clinical and microscopic characteristics of a very wide spectrum of melanocytic lesions. Key diagnostic features as well as potential pitfalls are highlighted in reader-friendly tables, facilitating quick reference in a busy diagnostic pathology practice. Pertinent up-to-date references are included and the index has been meticulously compiled.
TL;DR: It is found that SL significantly improved the survival of mice with small primary tumors and no difference was found in the incidence of lung metastases produced by B16-BL6 melanoma cells growing exclusively within regional lymph nodes and cells growing within the pinna.
Abstract: Lymphatic mapping and sentinel lymph node biopsy—also termed sentinel lymphadenectomy (SL)—has become a standard of care for patients with primary invasive cutaneous melanoma. This technique has been shown to provide accurate information about the disease status of the regional lymph node basins at risk for metastasis, provide prognostic information, and provide durable regional lymph node control. The potential survival benefit afforded to patients undergoing SL is controversial. Central to this controversy is whether metastasis to regional lymph nodes occurs independent of or prior to widespread hematogenous dissemination. A related area of uncertainty is whether tumor cells residing within regional lymph nodes have increased metastatic potential. We have used a murine model of primary invasive cutaneous melanoma based on injection of B16-BL6 melanoma cells into the pinna to address two questions: (1) does SL plus wide excision of the primary tumor result in a survival advantage over wide excision alone; and (2) do melanoma cells growing within lymph nodes produce a higher incidence of hematogenous metastases than do cells growing at the primary tumor site? We found that SL significantly improved the survival of mice with small primary tumors. We found no difference in the incidence of lung metastases produced by B16-BL6 melanoma cells growing exclusively within regional lymph nodes and cells growing within the pinna.
TL;DR: Imatinib mesylate (imatinib, Gleevec™; Novartis, Basel, Switzerland) has revolutionized the management of patients with advanced disease by targeting the aberrant kinase activity of Kit.
TL;DR: Comparison of CD99 and CD34 showed that the non‐tumoral periphery of DFSP was less probable to be CD99 positive, but this finding was not statistically significant.
Abstract: According to most authors, dermatofibrosarcoma protuberans (DFSP) and giant cell fibroblastoma (GCF) represent the adult and juvenile forms, respectively, of the same disease entity, as evidenced by similar morphology, an identical chromosomal translocation, and CD34 positivity. It has been shown that DFSP and nuchal-type fibroma (NTF) (which is also CD34-positive) are related lesions, and that there might possibly be a continuum between the two. In addition, NTF exhibits CD99 positivity. It was therefore, hypothesized that both DFSP and GCF would show similar immunopositivity for CD99. Archives of pathology at several institutions were searched for DFSP and GCF tissue blocks. A total of 29 DFSP and 5 GCF were analyzed by immunohistochemistry for expression of CD99. Twenty-three of 29 DFSP (79%) and 2 of 5 GCP (40%) expressed CD99. Comparison of CD99 and CD34 showed that the non-tumoral periphery of DFSP was less probable to be CD99 positive, but this finding was not statistically significant.
TL;DR: For melanocytic lesions of the eyelid with histologic features suggestive of cellular blue nevus, the correct diagnosis may mean a more conservative surgical resection and less likelihood of ocular tissue sacrifice and disfigurement as mentioned in this paper.
Abstract: Appropriate classification of melanocytic lesions in the eyelid region is important to avoid unnecessary surgery. Here we report 3 cases of cellular blue nevi in the lower eyelid, and make recommendations about approaching these challenging lesions. In each case, a diagnosis of cellular blue nevus was made using the following features: low mitotic rate, absence of necrosis, low Ki-67 reactivity, and mostly uniform HMB45 labeling. Furthermore, in each case there was either a prior diagnosis of melanoma or features worrisome for an atypical melanocytic lesion. For melanocytic lesions of the eyelid with histologic features suggestive of cellular blue nevus, the correct diagnosis may mean a more conservative surgical resection and less likelihood of ocular tissue sacrifice and disfigurement.