Indian Journal of Pharmacology (Indian J Pharmacol) 2018 | September-October | Volume 50 | Issue 5

EDITORIAL
	Developing and sustaining India's capacity for preclinical drug discovery	p. 225
	David I Lewis, Bhagirath K Patel, B Dinesh Kumar, Bikash Medhi DOI:10.4103/ijp.IJP_641_18
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RESEARCH ARTICLES
	Effect of Vaccinium macrocarpon on MK-801-induced psychosis in mice	p. 227
	Disha Shukla, Rajesh A Maheshwari, Kirti Patel, R Balaraman, Ashim Kumar Sen DOI:10.4103/ijp.IJP_74_17   OBJECTIVES: This study was aimed to investigate the effect of aqueous cranberry extract (ACE) on MK-801-induced psychosis in mice.MATERIALS AND METHODS: MK-801-treated mice were administered ACE (1 and 2 g/kg, p.o.) for 14 days. Various behavioral parameters and neurochemical estimations such as dopamine (DA), 5-hydroxytryptamine (5-HT), norepinephrine (NE), gamma-aminobutyric acid (GABA), glutamate, and glycine as well as markers of oxidative stress such as nitrite levels were measured.RESULTS: Psychosis-induced mice showed a significant elevation of immobility time in forced swim test, locomotor activity, and reduction in time of permanency in rota-rod test, escape latency time in Cook's pole test while treatment with ACE showed a significant alteration in above-mentioned behavioral parameters in MK-801-induced psychosis. Moreover, MK-801-induced psychosis in the mice showed a significant increase in DA, 5-HT, and NA levels and decrease in GABA, glutamate, and glycine levels in the brain. In contrast, treatment with ACE at both doses remarkably altered the neurochemical parameters. In addition, ACE-treated mice showed a substantial reduction in acetylcholinesterase, D-amino acid oxidase enzyme activity, and nitrite levels which were elevated by the administration of MK-801. CONCLUSIONS: Treatment with ACE once for 14 days (1 and 2 g/kg) significantly ameliorated the behavioral symptoms in experimentally induced psychosis by virtue of neuromodulation and decreased oxidative stress.
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	Efficacy of melatonin on sleep quality after laparoscopic cholecystectomy	p. 236
	Vaibhav Vij, Divya Dahiya, Lileswar Kaman, Arunanshu Behera DOI:10.4103/ijp.IJP_250_18   CONTEXT: Postoperative sleep and circadian rhythm disturbances were associated with prolonged postoperative convalescence, respiratory, and cardiovascular morbidity. Sleep disturbances have been shown to be due to decreased levels of circulating melatonin after surgery. If this sleep pattern and circadian rhythm are recycled, outcome after surgery could be improved. AIMS: The aim of this study was to observe the effect of melatonin on the quality of sleep in patients undergoing laparoscopic cholecystectomy (LC).SUBJECTS AND METHODS: Hundred patients of LC participated in this randomized, placebo-controlled, double-blind, clinical trial. Patients were randomized equally into Group A who received 6 mg melatonin tablets 45 min before sleep for 3 days after surgery and Group B who received placebo. RESULTS: Melatonin usage results in decrease in sleep latency (SL) as compared to placebo (13.6 ± 14.95 vs. 20.10 ± 16.18 min, P = 0.04). There was also increased total sleep duration (TSD) on postoperative day (POD) 1 (P = 0.004) and POD 2 (P = 0.001) in Group A. There was a decrease in daytime naps and night awakenings after surgery in Group A though it was not significant statistically. Subjective assessment of sleep on visual analog scale showed reduced sleep scores (P = 0.001 on POD 1 and 2) and decreased pain (P = 0.02 on POD 1) in Group A. Statistically significant difference was not observed in fatigue or general well-being among groups. CONCLUSIONS: Results in this study could demonstrate that melatonin as a single agent could improve the quality of sleep after LC by decreasing SL and increasing TSD.
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	In silico approach to study the metabolism and biological activities of oligomeric proanthocyanidin complexes	p. 242
	Sankar Jamuna, Ashokkumar Rathinavel, Sakeena Sadullah Mohammed Sadullah, Sivasitambaram Niranjali Devaraj DOI:10.4103/ijp.IJP_36_17   OBJECTIVES: Over the past three decades, numerous studies have focused on the biological activities of oligomeric proanthocyanidins (OPCs) in the prevention of many diseases such as neurodegeneration, atherosclerosis, tumorigenesis, and microbial infections. OPC has redox-active metabolites which could modulate the intracellular redox equilibrium to maintain the antioxidant homeostasis. This redox-modulating efficiency of OPC could provide new insights into therapeutic approaches that could reduce the burden of cardiovascular diseases. The main objective of this study was to explore the biological and metabolic activities of OPC using in silicoapproaches. METHODS: To validate the above objective, chemoinformatic tools were used to predict the metabolism of OPC after ingestion, based on both the ligand and structure of the constituent compounds. RESULTS: OPC showed possible sites for Phase I metabolism by cytochrome P450, and the metabolites obtained thereafter may be responsible for its biological activities. Absorption, distribution, metabolism, elimination, and toxicity properties showed efficient absorption, distribution, and metabolism of OPC, without toxicity. CONCLUSION: Thus, from the results obtained, OPC could be strongly recommended as a cardioprotective drug.
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	Antidiabetic potential of active fraction obtained from methanolic extract of Ichnocarpus frutescens: A possible herbal remedy	p. 251
	Mallu Srujana, Ranjana Ramesh, Lakshmi Devi Nanjaiah DOI:10.4103/ijp.IJP_24_18   OBJECTIVES: Ichnocarpus frutescens is a common plant used by tribal people and in Ayurveda for its high medicinal value. The purpose of the study was to investigate whether I. frutescens has any persuasive medicinal property to manage diabetes mellitus.MATERIALS AND METHODS: Initially, male albino Wistar rats were given intraperitoneal injection of streptozotocin-nicotinamide to induce diabetes, followed with the administration of active fraction obtained from the methanolic extract of I. frutescens for the next 28 consecutive days. Glibenclamide (25 mg/kg) was used as positive control. RESULTS: According to the results obtained, active fraction at a dose of 50 mg/kg body weight exhibited significant antihyperglycemic activity, which was evident with reduced blood glucose level up to 58.84%. The active fraction also showed improvement in serum lipid profile as well as regeneration of pancreatic β-cells in diabetic rats. Concurrent histopathological studies reinforce the effect of active fraction in healing pancreas, thus justifying the possible mechanism of its antidiabetic activity. CONCLUSION: The results of the present investigation lead credence to the use of I. frutescens in ameliorating the diabetic condition.
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	A comparative randomized study on effect of vaginally administered glyceryl trinitrate placebo on cervical ripening prior to induction of labor in overdue pregnancies	p. 260
	Özlem Dülger, Bulat Aytek Sik, Yilda Arzu Aba DOI:10.4103/ijp.IJP_182_18   OBJECTIVE: The aim of this study is to examine the effectiveness and adverse effects of local glyceryl trinitrate (GTN) application during labor compared with a placebo group. METHODS: The study consisted of 70 pregnant women with overdue pregnancies who presented to the hospital for labor induction between January 2009 and January 2011 in the Obstetrics Clinic of Istanbul Süleymaniye Gynecology and Obstetrics Education and Training Hospital. Vaginal suppositories-containing GTN (36/70) or placebo (34/70) was administered to the participants in a randomized fashion. The placebo and GTN involving vaginal ovules used in the study were prepared in the Pharmacy Department of Istanbul University Faculty of Pharmacy. Maternal effects during labor, rates of normal vaginal and C/S deliveries, the interval between the initial medication and delivery, and amount of total oxytocin used were compared between the GTN and placebo groups. RESULTS: There were no significant differences between the GTN and placebo groups regarding bishop scores, the interval between medication and delivery, delivery types, indications for cesarean section, and complications including hyperstimulation, tachysystole, uterine rupture, placental abruption, and uterine atony (P > 0.05). CONCLUSION: Our results revealed that there were no differences between GTN and placebo regarding their effect on cervical ripening in overdue pregnant women.
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	Oxaceprol versus tramadol for knee osteoarthritis: A randomized controlled trial	p. 266
	Kaushik Mukhopadhyay, Parasar Ghosh, Partha Ghorai, Avijit Hazra, Amal Kanti Das DOI:10.4103/ijp.IJP_633_16   OBJECTIVES: To assess efficacy and safety of oxaceprol, a hydroxyproline derivative with putative mechanism of action different from traditional nonsteroidal anti-inflammatory drugs, in symptomatic knee osteoarthritis, in comparison to tramadol. MATERIALS AND METHODS: A parallel group, double-blind, randomized controlled trial was conducted with ambulatory patients over 50 years age suffering from knee osteoarthritis causing pain of at least moderate intensity. Patients were randomized to receive either oxaceprol 200 mg thrice daily or tramadol 50 mg thrice daily for 12 weeks. The primary efficacy variable was symptom relief as assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) version 3.1 for pain, stiffness, and physical function. Responder rate (50% pain relief), patient's Clinical Global Impression (CGI), and rescue medication use were other outcomes measured. Vital signs, routine blood counts, tests of hepatorenal function and treatment-emergent adverse events were recorded for safety assessment.RESULTS: From 91 patients recruited, 43 on oxaceprol and 36 on tramadol were evaluable. The WOMAC scores declined significantly from baseline in each arm but remained comparable between groups throughout the 12-week study period. The CGI ratings and 50% responder rates were also comparable at the final visit. Differences in dose up-titration and rescue medication requirements were statistically nonsignificant. So also were the adverse event counts. Compliance was satisfactory in both groups. CONCLUSIONS:Efficacy and tolerability of oxaceprol were comparable to tramadol, and the drug can be considered as an alternative to low-potency opioids in the management of knee osteoarthritis.
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	A retrospective analysis of reporting of adverse drug reactions to oncology drugs: An experience from a national center of clinical excellence	p. 273
	Pramod Kumar Sharma, Arup Kumar Misra, Ajay Gupta, Surjit Singh, Puneet Dhamija, Puneet Pareek DOI:10.4103/ijp.IJP_544_17   INTRODUCTION: Adverse drug reaction (ADR) is a public health problem which constitutes one of the leading causes of morbidity and mortality worldwide. In India, only a few studies reported cancer chemotherapy-induced ADRs. The objectives of the present study were to assess the organ system involved, frequency, severity, and preventability of the ADRs occurred. MATERIALS AND METHODS: Data on ADRs of retrospective cohorts were extracted from the filled ADR forms received from the department of radiation oncology. Descriptive statistic was used to summarize and analyze the available data, namely patient demography, causality, severity, and preventability of the event. RESULTS: A total of 191 chemotherapy-induced ADR reports were received from 164 patients during the period March 2015 to August 2017. Almost three-fourth of the ADRs occurred in patients who were receiving regimens involving multiple drugs. Taxanes, alkylating agents, and platinum compounds were the common drug groups involved. The skin (n = 90) was the most frequently involved organ with alopecia and hyperpigmentation as most common manifestations. The severity (Hartwig and Siegel) and preventability scales (Modified Schumock and Thornton) indicated that most reactions were mild (54.45%) in nature and the majority of them were preventable. More than two-third (69%) of the reactions were related "possible" to the suspected drug as determined by the World Health Organization causality assessment. CONCLUSION: Chemotherapy-related ADRs among cancer patients are worrisome. It has a negative impact on patient quality of life and in addition increases cost of therapy. It is found that timely reporting of chemotherapy-related ADRs and having an effective ADR monitoring system in place ensure preventability of the ADRs in many cases. Oncologists, Radiotherapists and Onco-surgeons should be actively involved in ADR reporting (Onco-Pharmacovigilance) and exchange constructive information, update and educate each other about appropriate use of anticancer drugs. Onco-pharmacovigilance is the need of the hour and could be of immense value in reducing morbidity and mortality if practiced with utmost importance.
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	Ten units intravenous oxytocin over 2–4 h is as effective as 30 units over 8–12 h in preventing postpartum hemorrhage after cesarean section: A randomized controlled trial	p. 279
	Maria Cecilia, Reeta Vijayaselvi, Ramandeep Bansal, Latha Lakshmi, Ruby Jose DOI:10.4103/ijp.IJP_419_18   OBJECTIVES: Currently, recommended high-dose oxytocin regimen for the prevention of postpartum hemorrhage (PPH) following cesarean delivery (CD) is associated with maternal side effects frequency of which is greater with a higher cumulative dose and rapid administration of oxytocin. Here, we evaluated the efficacy of single-dose intravenous oxytocin over 2–4 h (total = 10 units) with oxytocin maintenance infusion for 8–12 h (total = 30 units) in postoperative CD women for the prevention of PPH. METHODS: The current double-blinded randomized controlled trial was carried out in a tertiary care institute in Southern India. The primary outcome measures included the following: (a) the need for additional uterotonics to control PPH and (b) significant deterioration of vital signs as assessed by pulse rate and blood pressure in the postoperative period. The secondary outcome measures were as follows: (a) significant difference (≥10% between preoperative and postoperative packed cell volume) and (b) need for blood transfusion. RESULTS AND CONCLUSIONS: Two hundred and seventy-one women were randomized into Group A (oxytocin = 10 units; n = 135) and Group B (oxytocin = 30 units; n = 136). Both the groups were comparable with regard to demographic characteristics. There was no difference in any of primary or secondary outcome measures in the two groups. Thus, low-dose oxytocin regimen is as effective as high-dose oxytocin regimen in the prevention of PPH in postoperative CD women.
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DRUG WATCH
	Rare occurrence of hand-foot syndrome due to paclitaxel: A rare case report	p. 284
	Pritam S Kataria, Pradip P Kendre, Apurva A Patel, Nahush Tahiliani, Vijay Bhargav, Honey Parekh DOI:10.4103/ijp.IJP_547_17   Hand-foot syndrome (HFS) is a relatively frequent adverse reaction to certain anticancer drugs. HFS is a type of dermatitis which has been most commonly described with 5-fluorouracil and capecitabine. However, HFS with paclitaxel is rare and has been reported sparingly in the literature. A 52-year-old male patient with recurrent carcinoma of the buccal mucosa was started on palliative chemotherapy regimen, injection paclitaxel (175 mg/m2) in combination with injection carboplatin. On post-chemotherapy day 13, the patient started developing pain, dysesthesia followed by bullae formation, and desquamation over palms and soles. Clinically, the patient had Grade 3 HFS characterized by symmetrical, tender skin lesions over the dorsal aspect of palms, and soles with desquamation necessitating interruption of treatment. Therefore, this case has been presented to be cognizant with this rare form of side effect with one of the most commonly used drug in oncology.
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Confocal Microscopy and Lentigo Maligna: An in vivo Pilot Study for the Assessment of Response to Imiquimod Therapy

Background: Reflectance confocal microscopy (RCM) is a noninvasive technique that provides real-time in vivo images of the epidermal layer. Imiquimod has been recommended as an alternative treatment in lentigo maligna (LM) when surgical excision is not the treatment of choice. In the present study we compare the results of in vivo RCM to the histopathological examination before and after treatment of LM with topical imiquimod. Methods: Thirty-four patients with confirmed LM were included. Imiquimod 5% was applied until a weeping erosion appeared in the LM-affected skin. Evaluation was performed by clinical examination, dermatoscopy, histopathology and RCM. Results: During the follow-up, 27 of 34 patients (79.42%) demonstrated a total tumor clearance by imiquimod treatment. In the treated area, a significant decrease of atypical cells was detected using RCM (p #x3c; 0.0001). Furthermore, a significant positive correlation in the detected atypical cells was shown using confocal microscopy and histology (p = 0.0001, r = 0.7335, respectively). Conclusion: In patients not suitable for surgical intervention imiquimod treatment is an appropriate treatment alternative. Thereby, in vivo RCM was demonstrated to be an excellent examining device, which not only allows diagnosis of LM, but also therapy and follow-up examinations. An important benefit of RCM, in contrast to conventional histopathology, is the simple handling with in vivo examination of epidermal skin without any pain for the patient.
Dermatology

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Dupilumab does not affect correlates of vaccine-induced immunity: A randomized, placebo-controlled trial in adults with moderate-to-severe atopic dermatitis

Publication date: January 2019

Source: Journal of the American Academy of Dermatology, Volume 80, Issue 1

Author(s): Andrew Blauvelt, Eric L. Simpson, Stephen K. Tyring, Lisa A. Purcell, Brad Shumel, Christopher D. Petro, Bolanle Akinlade, Abhijit Gadkari, Laurent Eckert, Neil M.H. Graham, Gianluca Pirozzi, Robert Evans

Background

The impact of dupilumab, an anti–interleukin (IL) 4 receptor α antibody that inhibits IL-4 and IL-13 signaling, on vaccine responses of patients with atopic dermatitis (AD) is unknown.

Objectives

To assess T-cell–dependent and T-cell–independent humoral immune responses to tetanus and meningococcal vaccines, IgE seroconversion to tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination, and dupilumab efficacy and safety.

Methods

In a randomized, double-blinded, placebo-controlled study (NCT02210780), adults with moderate-to-severe AD received dupilumab (300 mg) or placebo weekly for 16 weeks, and single doses of Tdap and quadrivalent meningococcal polysaccharide vaccines at week 12. Primary endpoint was proportion of patients achieving satisfactory IgG response to tetanus toxoid at week 16.

Results

In total, 178 patients completed the study. Similar positive immune responses (≥4-fold increase in antibody titer, or an antibody titer of ≥8) were achieved in the dupilumab and placebo groups to tetanus (83.3% and 83.7%, respectively) and meningococcal polysaccharide (86.7% and 87.0%, respectively). Dupilumab significantly decreased total serum IgE; most dupilumab-treated patients were Tdap-IgE seronegative at week 32 (62.2% dupilumab and 34.8% placebo). Dupilumab improved key AD efficacy endpoints (P < .001). Injection-site reactions and conjunctivitis were more common with dupilumab; AD exacerbations more frequent with placebo.

Limitation

Patients' prior vaccination status was not available before enrollment.

Conclusion

Dupilumab did not affect responses to the vaccines studied, significantly decreased IgE, and improved measures of AD severity versus placebo, with an acceptable safety profile.

Graphical abstract

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Dermatologic surgery

Publication date: January 2019

Source: Journal of the American Academy of Dermatology, Volume 80, Issue 1

Author(s): Michelle Xu

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Parental decisions for adolescent patients: Ethical considerations of information withholding

Publication date: January 2019

Source: Journal of the American Academy of Dermatology, Volume 80, Issue 1

Author(s): Jonathan M. Soh, Mary Gail Mercurio, Lisa A. Beck

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Video chat to prevent wrong site surgery

Publication date: January 2019

Source: Journal of the American Academy of Dermatology, Volume 80, Issue 1

Author(s): Ramona Behshad, Joseph Muccini

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Dermatology Calendar

Publication date: January 2019

Source: Journal of the American Academy of Dermatology, Volume 80, Issue 1

Author(s):

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Reply to: “Aspirin use and the risk of malignant melanoma”

Publication date: January 2019

Source: Journal of the American Academy of Dermatology, Volume 80, Issue 1

Author(s): Kelsey A. Orrell, Alfred W. Rademaker, Dennis P. West, Beatrice Nardone

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Aspirin use and the risk of malignant melanoma

Publication date: January 2019

Source: Journal of the American Academy of Dermatology, Volume 80, Issue 1

Author(s): Lenard M. Lichtenberger, Shelley Burge

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Reply to: “Kalava-induced foreign body reaction”

Publication date: January 2019

Source: Journal of the American Academy of Dermatology, Volume 80, Issue 1

Author(s): Mayra B.C. Maymone, Roopal V. Kundu, Neelam A. Vashi

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Kalava-induced foreign body reaction

Publication date: January 2019

Source: Journal of the American Academy of Dermatology, Volume 80, Issue 1

Author(s): Rachita Misri, Deepak Jakhar, Rakesh Gupta, Smriti Kumar

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Using a car phone holder for performing oculoscopy with a universal serial bus dermatoscope

Publication date: January 2019

Source: Journal of the American Academy of Dermatology, Volume 80, Issue 1

Author(s): Deepak Jakhar, Chander Grover

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Growth in the cost of biologics in Medicare beneficiaries, 2013 to 2016

Publication date: January 2019

Source: Journal of the American Academy of Dermatology, Volume 80, Issue 1

Author(s): Partik Singh, Jonathan I. Silverberg

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Dupilumab use in allergic contact dermatitis

Publication date: January 2019

Source: Journal of the American Academy of Dermatology, Volume 80, Issue 1

Author(s): Brian C. Machler, Calvin T. Sung, Evan Darwin, Sharon E. Jacob

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Pharmacy costs of specialty medications for plaque psoriasis in the United States

Publication date: January 2019

Source: Journal of the American Academy of Dermatology, Volume 80, Issue 1

Author(s): Eric J. Yang, Kristen M. Beck, Sahil Sekhon, Tina Bhutani

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Survey analysis on the management of moderately dysplastic nevi among academic dermatologists across the United States

Publication date: January 2019

Source: Journal of the American Academy of Dermatology, Volume 80, Issue 1

Author(s): Kristen M. Tessiatore, Hyunji Choi, Ambuj Kumar, Nishit S. Patel

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Analysis of national skin cancer expenditures in the United States Medicare population, 2013

Publication date: January 2019

Source: Journal of the American Academy of Dermatology, Volume 80, Issue 1

Author(s): Emily Stamell Ruiz, Frederick C. Morgan, Corwin M. Zigler, Robert J. Besaw, Chrysalyne D. Schmults

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Survival of patients with early invasive melanoma down-staged under the new eighth edition of the American Joint Committee on Cancer staging system

Publication date: January 2019

Source: Journal of the American Academy of Dermatology, Volume 80, Issue 1

Author(s): Lena A. von Schuckmann, Maria Celia B. Hughes, Rebecca Lee, Paul Lorigan, Kiarash Khosrotehrani, B. Mark Smithers, Adele C. Green

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Appropriate use criteria in dermatopathology: Initial recommendations from the American Society of Dermatopathology

Publication date: January 2019

Source: Journal of the American Academy of Dermatology, Volume 80, Issue 1

Author(s): Task Force/Committee Members, Claudia I. Vidal, Eric A. Armbrect, Aleodor A. Andea, Angela K. Bohlke, Nneka I. Comfere, Sarah R. Hughes, Jinah Kim, Jessica A. Kozel, Jason B. Lee, Konstantinos Linos, Brandon R. Litzner, Tricia A. Missall, Roberto A. Novoa, Uma Sundram, Brian L. Swick, M. Yadira Hurley, Rating Panel, Murad Alam, Zsolt Argenyi, Lyn M. Duncan, Dirk M. Elston

Background

Appropriate use criteria (AUC) provide physicians guidance in test selection, and can affect health care delivery, reimbursement policy, and physician decision-making.

Objectives

The American Society of Dermatopathology, with input from the American Academy of Dermatology and the College of American Pathologists, sought to develop AUC in dermatopathology.

Methods

The RAND/UCLA appropriateness methodology, which combines evidence-based medicine, clinical experience, and expert judgment, was used to develop AUC in dermatopathology.

Results

With the number of ratings predetermined at 3, AUC were developed for 211 clinical scenarios involving 12 ancillary studies. Consensus was reached for 188 (89%) clinical scenarios, with 93 (44%) considered "usually appropriate" and 52 (25%) "rarely appropriate" and 43 (20%) having "uncertain appropriateness."

Limitations

The methodology requires a focus on appropriateness without comparison between tests and irrespective of cost.

Conclusions

The ultimate decision to order specific tests rests with the physician and is one where the expected benefit exceeds the negative consequences. This publication outlines the recommendations of appropriateness—the AUC for 12 tests used in dermatopathology. Importantly, these recommendations may change considering new evidence. Results deemed "uncertain appropriateness" and where consensus was not reached may benefit from further research.

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Clinical spectrum of cutaneous melanoma morphology

Publication date: January 2019

Source: Journal of the American Academy of Dermatology, Volume 80, Issue 1

Author(s): Nikolai Klebanov, Nicole S. Gunasekera, William M. Lin, Elena B. Hawryluk, David M. Miller, Bobby Y. Reddy, Mitalee P. Christman, Derek Beaulieu, Suvithan Rajadurai, Lyn M. Duncan, Arthur J. Sober, Hensin Tsao

Background

Melanoma can mimic other cutaneous lesions, but the full spectrum and prevalence of these morphologic variants remain largely unknown.

Objective

To classify nonacral cutaneous melanomas into distinct morphologic clusters and characterize clusters' clinicopathologic features.

Methods

All pathologic melanoma diagnoses (occurring during 2011-2016) were reviewed for routine prebiopsy digital photographs (n = 400). Six dermatologists independently assigned lesions into 1 of 14 diagnostic classes on the basis of morphology. Image consensus clusters were generated by K-means; clinicopathologic features were compared with analysis of variance and χ².

Results

Five morphologic clusters were identified: typical (n = 136), nevus-like (n = 81), amelanotic/nonmelanoma skin cancer (NMSC)–like (n = 70), seborrheic keratosis (SK)–like (n = 68), and lentigo/lentigo maligna (LM)–like (n = 45) melanomas. Nevus-like melanomas were found in younger patients. Nevus-like and lentigo/LM-like melanomas tended to be thinner and more likely identified on routine dermatologic examinations. NMSC-like melanomas were tender, thicker, more mitotically active, and associated with prior NMSC. Typical and SK-like melanomas had similar clinicopathologic features.

Limitations

Cluster subdivision yielded diminished sample sizes. Visual assignment was performed without clinical context.

Conclusion

When primary cutaneous melanomas were assigned into diagnostic groups and subjected to novel consensus clustering, recurrent morphologic patterns emerged. The spectrum of these morphologies was unexpectedly diverse, which might have implications for visual training and possibly clinical diagnosis.

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