Pandemic Infl uenza as 21st Century Urban Public Health Crisis
December 2009 1963 1964. December 2009. December 2009

David M Bell firstname.lastname@example.com
Isaac B Weisfuse
Mauricio Hernandez-Avila
Carlos Del Rio
Xinia Bustamante
Guenael Rodier

Emerging Infectious Diseases •
Ministry of Health of Mexico
Mexico City, Mexico (M. Hernandez-Avila)

School of Public Health
Emory University Rollins
1600 Clifton Rd NE, Mailstop E0430333Atlanta, AtlantaGAUSA

Pandemic Infl uenza as 21st Century Urban Public Health Crisis

Emerging Infectious Diseases • www.cdc.gov/eid •
1512December 2009 1963 1964. December 2009. December 200910.3201/eid1512.091232Author affi liations: Centers for Disease Control and Prevention, Atlanta, Georgia, USA (D.M. Bell); New York City Department of Health and Mental Hygiene, New York, New York, USA (I.B. Rio); Pan American Health Organization, San Jose, Costa Rica (X. Bustamante); and World Health Organization, Ge-neva, Switzerland (G. Rodier) Address for correspondence: David M. Bell, Centers for Disease Control and Prevention,
The percentage of the world's population living in urban areas will increase from 50% in 2008 to 70% (4.9 billion) in 2025. Crowded urban areas in developing and industrialized countries are uniquely vulnerable to public health crises and face daunting challenges in surveillance, response, and public communication. The revised International Health Regulations require all countries to have core surveillance and response capacity by 2012. Innovative approaches are needed because traditional local-level strategies may not be easily scalable upward to meet the needs of huge, densely populated cities, especially in developing countries. The responses of Mexico City and New York City to the initial appearance of infl uenza A pandemic (H1N1) 2009 virus during spring 2009 illustrate some of the new challenges and creative response strategies that will increasingly be needed in cities worldwide.

A ccording to United Nations estimates, the percentage of the world's population living in urban areas will increase from 50% in 2008 to 70% (4.9 billion persons) in 2025. During 2007-2025, the number of cities with population 1-5 million will increase from 382 to 524, and the number of megacities (>10 million population, comprising the core city, suburbs, and continuously settled commuter areas) will increase from 19 to 27. Of the 27 megacities, 16 will be in Asia, 4 in Latin America, 3 in Africa, 2 in Europe, and 2 in North America. Currently, 1 in 25 persons lives in a megacity; in Latin America, the ratio is 1 in 7. In central Tokyo, the population density is 5,847 persons/ km 2 (1). Cities are increasing in developing countries and often have slums that lack basic services (2). The accelerating global trend toward megacities is a new paradigm of human existence and poses profound public health challenges. New approaches for surveillance, preparedness, and response will be needed because current strategies may not be easily scalable upward to address huge, densely populated areas, especially in developing countries.

In 2008, the World Health Organization (WHO) International Health Regulations (IHR) Coordination Department, in collaboration with Lyonbiopole (Lyon, France), held a consultation, Cities and Public Health Crises (1). Consultants stated that WHO and national guidance does not always adequately address the challenges their cities face, and they could learn much from each other. This article summarizes these challenges, illustrated by the initial appearance of infl uenza A pandemic (H1N1) 2009 virus during spring 2009 in Mexico City, Mexico, and New York (NYC), New York, USA (metropolitan area populations 20 million and 19 million, respectively). These megacities may not be representative of cities in low-income countries, which face more daunting problems. National surveillance detected an atypical increase in infl uenza-like illness (ILI) in mid to late February 2009 and a further increase in early to mid April. Anecdotal reports in April of increased hospitalizations of previously healthy young adults with severe pneumonia led to active surveil-lance in 23 hospitals in Mexico City and identifi cation of 47 such cases. Patient samples showed nonsubtypeable infl uenza A, identifi ed on April 23 as a novel infl uenza A virus of subtype H1N1. The Mexico City response was based on early adaptation of a pandemic infl uenza preparedness plan that had been developed for a virus originating abroad. After an expert meeting convened by the secretary of health, given the uncertain potential health impact, the president of Mexico invoked emergency powers; on April 24, community mitigation measures were implemented in Mexico City and the neighboring state of Mexico (3)(4)(5)(6)(7). These measures were announced and coordinated by the federal government, with participation of state authorities. The objective was to decrease transmission; elements included an intensive mass media campaign to inform the population about infl uenza, promote personal and environmental hygiene, request that sick persons stay home, and implement social distancing measures. Persons with ILI were encouraged to seek prompt medical care. Early in the epidemic, the federal government released antiviral drugs from the national strategic reserve and controlled their distribution. Ill persons and their close contacts had access to this medication free of charge. During the spring outbreak, an estimated 150,000 cases of ILI with 3,312 hospitalizations occurred in metropolitan Mexico City (H. Lopez-Gatell, pers. comm.).

Following the Mexican Pandemic Plan, a program of social mobilization was implemented through a multifaceted mass media saturation campaign featuring visual representations and a previously developed and tested message icon, Promi, to address Mexico City's heterogeneous population and literacy rates ( Figure 1). The private sector, including pharmacy chains, food stores, and cellular telephone companies, helped deliver health messages. The Mexican telephone company (Telmex) assembled a call center that received >5 million calls. Novel communication strategies included text messaging and mass emails; information from the Ministry of Health was transmitted through >140 million text, 60 million printed, and 18 million email messages. Multilingual health information materials also were provided to all international travelers entering and exiting through Mexican ports, and departing travelers underwent thermal screening.

Frequent hand washing and cough etiquette were promoted, and all government and private facilities open to the public were provided with alcohol gel and other disinfectants. Because of limited water availability in some areas or households, alcohol gel was distributed free. A mass media campaign promoting a healthy distance discouraged greeting others by hugging or kissing, common practice among Mexicans of all social strata. Military personnel distributed disposable surgical masks in public places; their use was recommended primarily for sick persons, but many healthy persons also wore them daily. Compliance with recommendations appeared to be high, although some persons wearing masks may have developed a false sense of security that took priority over cough etiquette and hand washing. When commercially available masks became scarce, some persons made their own, and disposal occasionally was problematic, resulting in littering. Over time, recommendations about cough and sneeze etiquette were followed least frequently.

All educational facilities were closed beginning April 24 in Mexico City and, soon after, nationwide. Parents were advised to keep children at home; authorities distributed educational materials for home use. By May 11, Figure 1. Sign hung on doorknobs containing information from the Mexican Ministry of Health promoting cough etiquette, using the communications icon Promi (3). Translation: "Wash your hands. Viruses are not permitted to enter here. When coughing or sneezing, cover your mouth with a disposable handkerchief or use your forearm, never your hands!" when educational facilities reopened, all schools had been thoroughly cleaned. Parents were requested to keep ill children home; peer pressure among parents to comply was high. Every day, upon arrival at school, children were screened for fever and respiratory symptoms. Ill children were sent home to receive care; return to school required a note from their primary healthcare provider granting medical clearance.

In addition to federal measures, on April 27, the mayor of Mexico City suspended dine-in service in all restaurants and similar establishments, allowing only take-out orders. Many restaurants simply remained closed. When affected businesses were allowed to reopen on May 6, social distancing measures (e.g., avoiding crowding) were encouraged, and hygiene measures were enforced ( Figure 2). Grocery stores and supermarkets remained open, with additional cashiers used to keep lines short. Persons in public places were advised to remain separated by at least 2 m. Large gatherings were cancelled or postponed, and entertainment venues, e.g., movie theaters, were closed. Professional sports matches were broadcast, but stadiums were closed to the public. Churches and temples also remained closed, with religious services broadcast over radio and television. When normal services resumed, communion cups and other shared objects were wiped with hand gel after each use. Mass transit operated normally. Masks were provided for drivers and passengers and buses and subway cars were cleaned frequently. Mitigation measures were broadly accepted by the public. Occasional early discrepancies between recommendations from offi cial and academic sources (e.g., regarding mask use) led to a few critical media reports without apparent consequence. Thousands of workplaces of all sizes in Mexico City and the rest of the country were closed for several days, taking a huge toll on the economy. The government provided no fi nancial compensation to businesses or workers. The economic impact of pandemic (H1N1) 2009 virus in Mexico during the spring is estimated as >$2.3 billion (0.3% of gross domestic product) (8).

Most important among the many lessons learned in Mexico is that preparation paid off. Although requiring adaptation, the preexisting pandemic plan and planning process facilitated intersectoral work, decision making, and rapid development of a public communications campaign. The availability of a national stockpile of antiviral drugs reassured the public. The participation of the secretary of health as the spokesman demonstrated high-level leadership. Clear and transparent communication was important because Mexico was entering mid-term elections, and some politicians hypothesized that the outbreak was a farce to distract Mexicans.

The outbreak also enabled detection of some weaknesses in the Mexican health system. In Mexico, health-care is provided by 3 major healthcare systems; thus compilation of epidemiologic information regarding hospitalizations was complex. However, after a few days, a system was devised that provided the necessary consolidated information. Laboratory capacity was inadequate for the challenges posed by the outbreak. At the onset of the outbreak, the Ministry of Health had no state-level laboratories with capabilities for infl uenza molecular diagnostics; all molecular diagnosis was centralized at the National Epidemiological Reference Laboratory in Mexico City. The Ministry of Health rapidly improved the national laboratory network and Mexico has now 28 laboratories (1 in nearly every state) with PCR molecular diagnostic capabilities. Although having a pandemic plan was useful, operationalizaton of the plan was less smooth. For example, procedures existed to close schools, but criteria for reopening them and the ability to reassure parents that reopened schools were safe did not.

NYC

Emergency preparedness planning in NYC accelerated after the World Trade Center and anthrax attacks of 2001 and in anticipation of an infl uenza pandemic. Novel syndromic surveillance systems monitor visits to hospital emergency departments, calls to emergency medical services, pharmacy sales, worker absenteeism, and outpatient clinic visits. For example, information is collected electronically for ≈90% of daily patient visits from 77% of emergency departments. Patients' age, sex, home postal code, and chief complaint, but not names, are transmitted daily to the NYC Department of Health and Mental Hygiene, where protocols identify and follow up signals that suggest increased community illness. During spring 2009, these systems were essential for real-time monitoring of the pandemic in NYC, e.g., documenting large increases in children with ILI seeking care at emergency departments) and for tracking its spread throughout the city from 1 school where it apparently was fi rst introduced and amplifi ed (9). Additional systems collect etiologic information from, for example, virologic studies on samples of outpatients and hospitalized patients with ILI. However, the fi rst indication to the health department of the outbreak of pandemic (H1N1) 2009 virus came from a school nurse telephoning a report of increased ILI at a single school. Subsequent surveillance and telephone surveys indicated ≈750,000-1 million persons in NYC had ILI during the spring outbreak (10).

When the fi rst cases were confi rmed, an extensive public communication campaign was implemented through Ready New York, a preexisting program of the NYC Offi ce of Emergency Preparedness (11). The program includes outreach to ethnic populations and translation into many languages. The principal messages were 1) wash hands thoroughly and frequently with soap and water; 2) avoid contact with persons who are obviously sick; and 3) if you get sick with any cold or infl uenza, stay home from work or school, and avoid contact with others as much as possible During the epidemic peak, the mayor and health commissioner held frequent press conferences in English and Spanish. A NYC government information hotline (311) previously had been established and featured live operators 24/7, with 98% of calls answered within 30 seconds. During the spring outbreak of pandemic (H1N1) 2009, ≈54,000 calls to 311 about infl uenza and a smaller health department hotline were answered. An electronic health alert network and conference calls provided messages to healthcare providers.

Aside from the public messages, community mitigation measures focused on selective closure of schools. Household contacts of case-patients were not quarantined, businesses were not closed, and public gatherings were not cancelled unless they involved closed schools. School closures were decided on an individual basis (known as "reactive" closures, based on visits for ILI to the school health nurse and on other factors, such as the ability of students to comply with respiratory hygiene) rather than "preemptively" (i.e., before cases in the school but with reports of cases in other schools in the subdistrict or district). Approximately 50 schools closed, for ≈1 week each.

The NYC emergency stockpile of antiviral drugs was not used because normal distribution channels suffi ced. Occasional reports of spot shortages required rapid investigation and highlighted the need for close communication with private distributors. If the stockpile had been needed, antiviral drugs would have been distributed to community health centers, public clinics, and hospitals. Distribution of vaccine for pandemic (H1N1) 2009 in NYC will depend on indications for use, availability, and urgency of administration. Vaccine will be prioritized for high-risk populations (12). Mass vaccination campaigns will use 200 point-of-distribution sites developed to meet possible needs for anthrax prophylaxis, e.g., school buildings throughout the city that each could serve ≈40,000 persons.

Problems included basing decisions on a pandemic severity index because, at the pandemic onset, its case-fatality ratio was uncertain. Despite previous planning, several school dismissal issues had never been entirely resolved, including the objectives of closure in a less severe pandemic (i.e., to protect high-risk students, all students, families; to slow community transmission; to allay public fears). The effectiveness of school closure in meeting these objectives was uncertain, as was the extent to which benefi ts justifi ed the secondary impact, including interrupting the academic program, parental work loss, and disruption of services provided at school (e.g., free breakfast and lunch to children from low-income families, therapy for students with special needs).

Operational questions included criteria for school dismissal and reopening and diffi culties in monitoring ILI and even absenteeism rates among students. Absenteeism data were often unavailable to the health department until midafternoon, relatively late to notify parents about closure decisions for the next school day. Instructions were not given for children to remain at home, and some may have recongregated elsewhere, such as in public libraries, while their parents were at work (13). News of school closures in NYC led to questions from parents in suburban jurisdictions about why their schools remained open, even though they had no known cases. Individual school closings showed the interconnectedness between schools, such as when siblings or neighbors attended different ones. The issue of worker or business compensation for lost time from work to care for ill children remains diffi cult. On the basis of this experience, in the 2009-10 school year, NYC is urging parents to keep sick children home and emphasizing infection control at school but will close a school only as a last resort. Closure decisions will be made on an individual basis, taking into account whether infection control practices could be improved and whether a high percentage of students have high-risk medical conditions (10).

During spring 2009, emergency departments were overcrowded with the worried ill, despite many announcements about indications for persons with ILI to seek medical care. In the fall and winter of 2009 hospitals are prepared to open additional nonemergency ILI care sites (e.g., at primary care clinics). A new 1-stop infl uenza Web portal provides information, as well as locations of clinical sites, and a call center staffed by nurses accessed through the 311 hotline provides guidance to persons with ILI (10).

In the city jail, cases of pandemic (H1N1) 2009 led to screening and control measures. These included isolation and cohorting of ill prisoners, and quarantine of those who had been exposed to them, to limit the spread of infection in the prison and court systems.

Health department staffi ng to meet surge needs posed challenges, including accessing and training staff from other parts of the health department, especially physicians, and the need to ensure staff time off to prevent burnout. Keeping policies and press releases consistent in the face of changing science and policies required constant attention. Internet survey instruments were effectively used to collect epidemiologic data, as in the initial high school student outbreak (9).

Issues for Cities

The experiences from the response to the emergence of pandemic (H1N1) 2009 virus in Mexico City and NYC highlighted several challenges raised at the WHO consultation (1). These include response coordination, surveillance and monitoring of illness trends, disease containment and mitigation, delivery of countermeasures, and public communication.

Response Coordination

Multiple government agencies serve large urban areas. Citizens frequently live, work, attend school in, and commute through different jurisdictions. Different political parties may control national, state or provincial, suburban, and city governments. Fringe groups or gangs may effectively control some areas. Incident or unifi ed command systems can be useful approaches to crisis coordination (14,15). In Mexico City and NYC, advance planning, political leadership at the highest levels, and collaboration among public health and emergency management agencies were particularly important.

Coordination with the private sector often is not well established. Businesses can assist, notably by providing health messages and enabling infectious workers to remain home (16). Large companies may have contacts with city leaders, but most are small to medium-sized enterprises with which coordination may be diffi cult. Multinational corporations, common in cities, may be subject to homecountry infl uences. Response coordination with nongovernment, community, and faith-based organizations also is important. Outbreaks in cities near international borders require coordination with foreign partners.

Surveillance and Monitoring of Illness Trends

Emerging challenges in cities include the vertical dimension (high-rise apartment blocks), travelers, and persons who do not have fi xed addresses or who live in slums. Novel approaches for illness reporting and population surveys may include use of cell phones and the Internet. Illness surveillance ultimately depends on the organization and provision of health services; cities with universal health coverage will have important advantages (17). Outbreak recognition still often depends on alert clinicians; technology-based systems notwithstanding, a school nurse provided the fi rst indication of the infl uenza outbreak in NYC.

Disease Containment and Mitigation

Although not generally a problem in Mexico City or NYC during spring 2009, in a larger outbreak in a lowerincome country, home isolation or quarantine may be diffi cult or impossible for large urban families living in 1 or 2 rooms. Contact tracing is problematic in cities, given the frequency of anonymous interactions. Innovative use of nonhealth databases and 3-dimensional mapping, including cell phone records and global positioning technologies, may be helpful but may pose privacy issues.

Decisions regarding school dismissal are problematic because effectiveness for disease mitigation is diffi cult to quantify, and operational aspects often are uncertain, whereas the potential for societal disruption is considerable. Analysis is pending of the different approaches taken by Mexico City and NYC during spring 2009, but both have kept schools open during the fall, because pandemic severity has remained comparable with that in the spring. This approach is consistent with updated guidance from WHO and the US Centers for Disease Control and Prevention (18,19). Many questions remain about how to implement social distancing and infection control measures in typical city venues, including schools, institutions of higher education, healthcare institutions, mass transit, workplaces, and marketplaces. These issues are even more diffi cult in developing countries. Many cities have international airports and may need to assist in health screening of passengers; provide medical care to ill passengers; and accommodate stranded passengers, including those in quarantine. Evacuation of a city poses additional public health challenges (17,20).

Delivery of Countermeasures

Rapid delivery of countermeasures, e.g., drugs and vaccines, is diffi cult even for persons with known, fi xed addresses, but more so for persons in slums, travelers, undocumented persons, and homeless persons, as well as the elderly and homebound. Measures taken in Mexico City and NYC during spring 2009 appear to have been sufficient, but these systems are being tested again during the 2009-10 winter season.

Public Communication

WHO outbreak communication guidelines emphasize building and maintaining trust, announcing information early, ensuring transparency, listening to the public, and planning ahead (21). The generally successful public communication campaigns of Mexico City and NYC incorporated these approaches. In addition to traditional mass media and the Internet, they also used cell phones and text messaging, which may offer useful models for developing countries. Cell phone networks may need to prioritize health or emergency messages, improved robustness to permit high traffi c during emergencies, and redundancy in case transmitting towers are destroyed (e.g., in a storm). Text messages can be targeted geographically, e.g., to phones locked on to a particular transmitting tower at the time of the message. This approach could be useful for broadcasting localized alerts and instructions, such as locations of vaccination clinics.

Discussion

Cities are the norm of global development in the 21st century. As cities become larger and more crowded, traditional guidance for detecting and responding to public health crises requires innovation. Modifi ed guidance may be helpful, but new strategies, technologies, and metrics also will be needed.

Preliminary accounts of response to pandemic (H1N1) 2009 during spring 2009 in 2 world megacities offer grounds for optimism. In each case, advance planning laid the foundation for enhanced surveillance and a generally effective response, made possible by an extensive public communications campaign and effective political leadership. On the other hand, challenges emerged that would have been amplifi ed if the illness had been more severe or the period of societal disruption prolonged. Development of new guidance and approaches requires collaboration among large cities, as well as research and evaluation to identify best practices for cities with different resource levels, particularly for implementing core capacity requirements under the revised IHR in a world where most persons now live in urban environments. The IHR require all countries to have core capacity for disease "surveillance, reporting, notifi cation, verifi cation, response and collaboration activities" by 2012 (22,23). These requirements must be implemented in urban environments, but they are based on traditional public health levels (local, intermediate, and national), which are less clearly defi ned for large urban agglomerations. All national governments have committed themselves to IHR implementation; municipalities must play a central role but may not be aware of their obligations or able to meet them. Many partners will be important, including businesses, which may not realize their stake in IHR implementation (24). Sharing of experience and research is needed to develop strategies and best practices that can be considered by similar cities worldwide.

Figure 2 .
2A reopened restaurant in Mexico City, Mexico, illustrating mask use by the person greeting entering customers and a hand hygiene dispenser that all entering customers were required to use, May 2009. Photo courtesy of Carlos del Rio.
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 15, No. 12, December 2009
AcknowledgmentsWe thank the many members of the Mexican Ministry of Health, New York City Department of Health and Mental Hygiene 2009 H1N1 Infl uenza Investigation Team, the US Centers for Disease Control and Prevention, Pan American Health Organization, and World Health Organization staff for management of and response to the spring pandemic; Carlos Santos-Burgoa and Hugo Lopez-Gatell for providing valuable information and comment; and Sophia Desillas, Christian Mathiot, and Daniel Rutz for reviewing the manuscript Dr Bell is a medical epidemiologist working on the pandemic (H1N1) 2009 response at the Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
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Highly enhanced gas sensing in single-walled carbon nanotube-based thin-film transistor sensors by ultraviolet light irradiation

Tingting Chen
Liangming Wei
Zhihua Zhou
Diwen Shi
Jian Wang
Jiang Zhao
Yuan Yu
Ying Wang
Yafei Zhang
Highly enhanced gas sensing in single-walled carbon nanotube-based thin-film transistor sensors by ultraviolet light irradiation
N A N O E X P R E S SSingle-walled carbon nanotubesGas sensorUV radiationThin-film transistor
Single-walled carbon nanotube (SWCNT) random networks are easily fabricated on a wafer scale, which provides an attractive path to large-scale SWCNT-based thin-film transistor (TFT) manufacturing. However, the mixture of semiconducting SWCNTs and metallic SWCNTs (m-SWCNTs) in the networks significantly limits the TFT performance due to the m-SWCNTs dominating the charge transport. In this paper, we have achieved a uniform and high-density SWCNT network throughout a complete 3-in. Si/SiO 2 wafer using a solution-based assembly method. We further utilized UV radiation to etch m-SWCNTs from the networks, and a remarkable increase in the channel current on/off ratio (I on /I off ) from 11 to 5.6 × 10 3 was observed. Furthermore, we used the SWCNT-TFTs as gas sensors to detect methyl methylphosphonate, a stimulant of benchmark threats. It was found that the SWCNT-TFT sensors treated with UV radiation show a much higher sensitivity and faster response to the analytes than those without treatment with UV radiation.

Background

Recently, there are many reports on the use of singlewalled carbon nanotubes (SWCNTs) for fabricating a chemical sensor [1]. The SWCNTs with every atom on the surface are expected to exhibit excellent sensitivity toward absorbates [2,3]. SWCNTs also possess good environmental stability, excellent electronic properties, and ultrahigh ratio of surface to volume [4]. These features make SWCNTs ideal sensing materials for compact, low-cost, low-power, and potable chemical sensors [5]. Multiple types of SWCNT-based chemical sensors, such as chemiresistors [6,7], chemicapacitors [8], and fieldeffect transistors (FETs) [9], have been developed for sensing application, but the SWCNT-FETs offer several advantages for sensing including the ability to amplify the detection signal with the additional gate electrode [10]. Since Kong et al. first made use of SWCNT-FETs to detect NO 2 and NH 3 [11], the SWCNT-FETs have been successfully used to detect a variety of gases or chemical vapors, such as formaldehyde [12], O 2 [13], organophosphor [6,7], and TNT vapors [14]. It has been shown that the SWCNT-FETs exhibit significant conductance change upon exposure to absorbed molecules. Despite these significant progresses made in this field, the fabrication of high-performance SWCNT thin-film transistor (TFT) sensors still faces a big challenge due to the coexistence of metallic and semiconducting nanotubes (denoted as m-SWCNTs and s-SWCNTs, respectively) within the conducting channels [10]. In these unsorted SWCNT-TFTs, the electrical properties of the SWCNT networks are dominated by the m-SWCNTs in which small shifts of the Fermi level do not result in a substantial change in the density of state at the Fermi level, thus providing a lower electronic response upon analyte interaction with nanotubes [10,11].

Several approaches have been developed for obtaining SWCNT-FETs with pure s-SWCNT in the channels such as selective synthesis of s-SWCNTs [15][16][17][18], posttreatment [19][20][21], and selective etching of m-SWCNTs [22,23]. Gomez et al. have reported the method of using light irradiation to induce the metal-to-semiconductor conversion of SWCNTs for transistors based on both aligned and individual nanotube devices [24]. This method increased the channel current on/off ratio up to 10 5 in the SWCNT transistors. Roberts et al. reported a self-sorting method to enrich and align the s-SWCNT on the surface of silicon and polymeric films by controlling the substrate surface chemistry [25]. It was found that the aligned nanotube networks enriched with s-SWCNT showed a much higher sensitivity to analytes than those fabricated with random networks.

Random nanotube networks are easily deposited from the solution and represent an attractive path to large-scale device manufacturing [26][27][28]. However, they suffer from the mixture of s-SWCNTs and m-SWCNTs in the network, often resulting in a low on/off ratio due to the m-SWCNTs dominating the charge transport. Wang et al. [27] reported on the deposition of uniform and highdensity s-SWCNT random networks from a s-SWCNT solution onto a wafer using an assembly method. These s-SWCNT-TFTs show on/off ratios larger than 10 4 . However, this technology requires pre-separating 95% enriched s-SWCNTs. Here, we reported on the deposition of random SWCNT networks from the SWCNT solution on the wafer and then radiated the nanotube networks utilizing UV to fabricate SWCNT-TFT sensors with high performance. A remarkable increase in the channel current on/off ratio from approximately 11 to 5.6 × 10 3 was observed after UV irradiation. We also used these SWCNT-TFTs to detect methyl methylphosphonate (DMMP), a stimulant of benchmark threats. The SWCNT-TFTs treated with UV radiation show a much higher sensitivity to the analytes than those without treatment with UV radiation.

Methods

Materials

The carboxylic acid-functionalized SWCNTs were obtained from Carbon Solutions Inc. (Riverside, CA, USA). The Si/ SiO 2 wafer used is an n-doped Si (100) wafer with 300-nm oxide layer on the top of the Si wafer. DMMP and 3-aminopropyltrimethysilane (APS) were purchased from Sigma-Aldrich (St. Louis, MO, USA). Deionized water, ethanol, acetone, and toluene were used throughout all processes for cleaning. All reagents were analytical grade and were used without further purification.

SWCNT network deposition and sensor fabrication

To fabricate our gas sensors, the Si/SiO 2 wafer substrate was ultrasonically rinsed with toluene, acetone, ethanol, and deionized water, followed by cleaning with a piranha solution (98% H 2 SO 4 :30% H 2 O 2 = 3:1 (v/v)) for 2 h at 80°C. This clean wafer was immersed in APS aqueous solution (1.5 mM) for 2 h and then kept in a vacuum evaporator at 120°C for 1 h to form the amino-terminated monolayer on the surface of the Si/SiO 2 substrate. The purified SWCNTs were ultrasonically dispersed in deionized water for 2 h. The pretreated Si/SiO 2 substrate modified with an APS monolayer was immersed in the SWCNT suspension, followed by rinsing with ethanol and deionized water and drying with the aid of nitrogen flow. The morphology of the deposited SWCNTs was characterized by scanning electron microscopy (SEM; JSM-7401F, JEOL Ltd., Akishima, Tokyo, Japan).

The SWCNT-TFT sensors were fabricated using the standard microfabrication procedures in our previous report [7]. The interdigitated electrode fingers were made by sputtering 10 nm Cr and 180 nm Au onto the patterned photoresist mold. We introduced a lift-off process to remove the photoresist. Finally, the electrodes were ultrasonically rinsed in acetone and ethanol repeatedly, washed with deionized water thoroughly, and then dried by nitrogen flow before they were used. The UV light radiation wavelength utilized is 250 to approximately 360 nm, and the SWCNT-TFT sensor was exposed to the UV light for 0 to 1 h with a distance of 10 cm.

Sensor testing system

The homemade sensor testing system was established as in the previous reports [7]. Nitrogen, used as carrier gas, flowed through a porous glass-disc bubbler containing liquid DMMP to form DMMP vapor, and then, this DMMP vapor was mixed with the diluting N 2 in a stainless steel. The output flow ratio of the diluted DMMP vapor was controlled by mass flow controllers. The different concentrations of DMMP were produced by regulating the flow ratio of the dilution gas to the flow rate of the carrier gas. The DMMP vapor was delivered into the sensing chip to test the sensor performance. Before testing, the sensor was cleaned by UV for about 2 min to remove the absorbed impurity from the SWCNT network (meanwhile, the conductance was monitored to avoid etching SWCNTs) and then exposed to the DMMP.

The electrical signal of the sensor was monitored using a semiconductor parameter analyzer (Agilent 4156C, Agilent Technologies Inc., Santa Clara, CA, USA). After a stable baseline electrical signal was obtained, the DMMP vapor with the required concentration was introduced, and all sensing measurements were carried out at room temperature. The DMMP was desorbed from the SWNT surface by N 2 blowing together with illumination with a lamp (the wavelength was 710 nm, and the power was 200 W).

Results and discussion

The uniform and high-density SWCNT networks on the Si/SiO 2 wafer were fabricated with a solution-based selfassembly method [7,27]. Briefly, the Si/SiO 2 substrate was first functionalized with an amino-terminated monolayer. The carboxylic acid-functionalized SWCNTs de-bounded and dispersed in the water were easily absorbed and deposited on the amino-functionalized Si/SiO 2 substrate via electrostatic interaction. Following nanotube deposition was the fabrication of SWCNT-TFTs. The source and drain electrodes were patterned by standard photolithography. The silicon substrate acts as a back gate, while SiO 2 is used as the back gate dielectric. The schematic and SEM images of the SWCNT-TFT structure were shown in Figure 1a,b respectively. The electrodes possess a channel length of 600 μm and a channel width of 10 μm. The SEM images show that the high density and uniform deposition of SWCNT networks bridge the source and the drain electrodes ( Figure 1c). We also took the SEM images at nine different locations on the wafer to determine the deposition uniformity of the SWCNT networks (Figure 1d,e). It can be seen that the uniform and high-density nanotube networks were achieved throughout the 3-in. wafer, suggesting that the solution deposition approach is feasible to manufacture devices on a large scale. Figure 2 shows the SEM images of the SWCNT networks after irradiation by UV in air. It was found that the nanotube density decreased with an increase of the irradiation time, and at last, the nanotubes were completely removed from the wafer when a 60-min irradiation was applied.

We study the electrical performance of the SWCNT-TFTs. Figure 3 shows the source-drain current current   (I ds )-source-drain voltage (V ds ) curves of typical SWCNT-TFTs before and after UV radiation. The I ds -V ds curves were found to be very linear for V ds between −1 and 1 V, indicating the Ohmic contact between nanotubes and the electrodes (Figure 3a) [14,27]. After irradiation for 5 to 20 min, the I ds -V ds curves remain linear, but a significant decrease in the current was observed because nanotubes were etched from the channels by UV radiation. The SWCNT-TFTs completely lost the conductance after 30 min of illumination. The transfer characteristic (I ds versus V g ) of the sensor was measured using the Si substrate as a back gate. The measurement was operated at a constant source-drain voltage of 0.5 V and gate voltage between −20 and +20 V. As shown in Figure 3, the SWCNT device shows a p-type semiconductor behavior with holes as the majority carriers, evidenced by the decreasing electrical conductance when gate voltage (V g ) was swept from negative to positive values. The on/off ratio of the untreated SWCNT-TFTs is low (approximately 11) due to the contribution of the m-SWCNTs. After 5 to 20 min of light irradiation, the SWCNT-TFTs retained a p-type semiconductor behavior, but the on/off ratios increased from approximately 11 to approximately 5.6 × 10 3 , suggesting that most of the m-SWCNTs were etched from the channels.

The energy absorbed by SWCNTs is related to the light wavelength and intensity. The theoretical calculation has confirmed that the formation energy of m-SWCNTs is higher than that of the same-diameter s-SWCNTs [29,30] and that the m-SWCNTs show a higher chemical reactivity due to more abundant delocalized electronic states [31]. UV irradiation in air generated oxygen radicals and ozone, which are strong gas-phase oxidants [32]. The m-SWCNTs were easily oxidized by these oxidants and removed from the wafers as shown in Figure 4 [31,32]. The UV-assisted photo-oxidation could also increase defect density on the sidewall of nanotubes due to the increase in the sp 3 nature of irradiated nanotubes [24]. It is known that the conversion of sp 2 to sp 3 sites may lead to π-electron localization that can open the bandgap of metallic nanotubes and result in the conversion of m-SWCNTs to s-SWCNTs [24]. Both of the possible reasons might account for the high on/off ratio of the UVirradiated SWCNT-TFT devices. However, the significant decrease in the nanotube density as shown in the SEM images suggested that the etching of m-SWCNTs from the networks may be the main reason for the high performance of TFT devices.

The SWCNT-TFTs were used to detect DMMP, a stimulant of benchmark threats. The conductance between two electrodes was measured to investigate the sensory response, and the change in conductance (R) is defined as R = ΔG/G 0 = (G − G 0 )/G 0 , where G 0 and G are the conductance of nanotubes before and after exposure to the testing gas, respectively. Figure 5 shows the responses of the SWCNT networks to 0.73 ppm of DMMP at a constant source-drain voltage of 0.5 V and  gate voltage of 0 V. It can be seen that the resistance of the device increased upon exposure to 0.73 ppm of DMMP, and the conductance change was 17% (with a response time of 2 min) for the irradiated sensors, compared to only 2.2% conductance change for non-irradiated sensors. The irradiated SWCNT sensors show seven times higher sensitivity than those without irradiation. The sensor responses were also investigated when the SWCNT-TFTs were operated at gate voltage of −10 V at the same concentration of DMMP ( Figure 6). A pronounced increase in the sensitivity of SWCNT-TFTs was also observed after the SWCNT network was irradiated with UV light. For instance, the irradiated SWCNT-TFT sensor gave a 22% conductance change upon exposure to 0.32 ppm of DMMP, whereas only 2% conductance change was observed for the unirradiated sensor under the same concentration of DMMP. The reason for these different response behaviors is that for the unirradiated SWCNTs, the electrical properties of the SWCNT network are dominated by the m-SWCNTs in which small shifts of the Fermi level do not result in a substantial change in the density of state at the Fermi level and, thus, in the charge carried in the nanotubes [10,11]. After radiation, the channel conductance was dominated by s-SWCNT, from which a donation or injection of one electron could significantly change the conductance of SWCNTs, leading to a fast response and high sensitivity toward analytes. DMMP is a typical electron-donating molecule, and s-SWCNTs are p-type semiconductors with holes as the majority carriers in the nanotubes. Adsorption of DMMP onto the s-SWCNT leads to a charge transfer from the DMMP molecule to the nanotubes [9]. This charge transfer reduced the holes carried in the nanotubes and decreased sample conductance. Figure 6 also shows that applying a negative gate bias (V g = −10V) can enhance the sensitivity. As an electron donator, the adsorption of DMMP on the p-type SWCNTs is equivalent to applying a positive chemical gate voltage. From the I ds -V g curve (Figure 3h), a sharp slope was observed at this gate bias (−10 V). So, a large response is expected due to the positive chemical gate effect of the DMMP adsorption.

Conclusions

We reported the deposition of uniform and high-density SWCNT networks from the SWCNT solution on the wafer and then used these nanotube networks to fabricate SWCNT-TFT sensors. UV irradiation was utilized to etch m-SWCNTs and (or) convert m-SWCNTs to s-SWCNTs. A remarkable increase in the channel current on/off ratio from approximately 11 to 5.6 × 10 3 was observed after UV irradiation. We also used these SWCNT-TFT sensors to detect DMMP. It was found that the irradiated SWCNT-TFT sensors show a much higher sensitivity to the analytes than those without treatment with UV radiation. Our work provides a simple and efficient approach to a largescale fabrication of SWCNT-TFT sensors and solves the problem of low on/off ratio in the nanotube-based TFTs when the random SWCNT network is used.

Figure 1
1Schematic and SEM images. The (a) schematic and (b) SEM image of the SWCNT-TFT structure. (c) SEM image of SWCNT bridging the conducting channel. (d) SEM images showing SWCNTs deposited at different positions on the (e) electron patterning wafer.

Figure 2
2SEM image of SWCNT networks before and after UV irradiation. (a) Before UV irradiation; after (b) 5, (c) 10, (d) 20, (e) 30, (f) 40, and (g) 60 min of UV irradiation.

Figure 3 I
3ds versus V ds plots at different gate voltages (V g ) for SWCNT-TFT gas sensors. I ds versus V ds plots after (a) 0, (c) 5, (e) 10, and (g) 20 min UV radiation (V g is varied from −10 to 10 V in 2-V steps). The corresponding I ds -V g plots of the SWCNT-TFTs after (b) 0, (d) 5, (f) 10, and (h) 20 min of UV radiation (V ds = 0.5 V, V g = −20 to approximately 20 V).

Figure 4
4The schematic diagram for etching of m-SWCNTs from SWCNT networks.

Figure 5
5Conductance change versus time recorded with the sensor responses to 0.73 ppm of DMMP. Without (black) and with 20 min of UV radiation (red). I ds = 0.5 V, V g = 0 V.

Figure 6
6Conductance change versus time recorded with the sensor responses to 0.32 ppm of DMMP. (a) Without and (b) with 20 min of UV radiation. I ds = 1 V, V g = −10 V.
http://www.nanoscalereslett.com/content/7/1/644
AcknowledgmentsWe thank for the financial support from the National Natural Science Foundation of China (No. 51272155) and the Foundation for SMC Excellent Young Teacher in Shanghai Jiao Tong University.Competing interestsThe authors declare that they have no competing interests.Authors' contributions TTC performed the experiment and measured the SEM, electronic, and gas response data. LMW designed the experiments and wrote the manuscript. DWS helped in the technical support for the experiments. YY participated in the measurements. JW and JZ provided useful suggestions. ZHZ and YW helped analyze the characterization results. YFZ supervised all of the study and provided financial support. All authors read and approved the final manuscript.
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Highly enhanced gas sensing in singlewalled carbon nanotube-based thin-film transistor sensors by ultraviolet light irradiation. Chen , Convenient online submission 7 Rigorous peer review 7 Immediate publication on acceptance 7 Open access: articles freely available online 7 High visibility within the fi eld 7. Cite this article as. Retaining the copyright to your article Submit your next manuscript at 7 springeropen.comCite this article as: Chen et al.: Highly enhanced gas sensing in single- walled carbon nanotube-based thin-film transistor sensors by ultraviolet light irradiation. Nanoscale Research Letters 2012 7:644. Submit your manuscript to a journal and benefi t from: 7 Convenient online submission 7 Rigorous peer review 7 Immediate publication on acceptance 7 Open access: articles freely available online 7 High visibility within the fi eld 7 Retaining the copyright to your article Submit your next manuscript at 7 springeropen.com


Concurrent malignant melanoma and cutaneous involvement by classical hodgkin lymphoma (CHL) in a 63 year-old man

Alejandro A Gru
Dongsi Lu
Concurrent malignant melanoma and cutaneous involvement by classical hodgkin lymphoma (CHL) in a 63 year-old man
C A S E R E P O R T Open AccessMalignant melanomaClassical Hodgkin lymphomaBone marrow transplant
Classical Hodgkin lymphoma (CHL) is a lymphoproliferative disorder that has a bimodal age distribution, affecting young and elderly individuals, and is curable in more than 90% of patients. Here we report the coexistence of cutaneous CHL and malignant melanoma as the presentation of papules and a plaque, in an individual with remote history of systemic CHL. One of the biopsies showed a mononuclear cell infiltrate with Reed-Sternberg (RS) like cells that were positive for CD30 and CD15, but negative for CD45. A second concurrent biopsy showed an atypical melanocytic proliferation with significant pagetoid spreading and diffuse Melan-A staining. Based on morphology alone, it is almost impossible to distinguish CHL from other primary cutaneous lymphoproliferative disorders, such as CD30+ lymphoproliferative disorder (lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large-cell lymphoma), or even tumor stage mycosis fungoides when the epidermotropism is minimal. Additionally, bizarre melanocytic cells can also appear similar to RS cells. Our case illustrates the first case report of malignant melanoma and CHL in a patient presenting simultaneously. Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/ vs/8979757349937225

Introduction

Classical Hodgkin lymphoma (CHL) is a lymphoproliferative disorder that has a bimodal age distribution, affecting young and elderly individuals, and is curable in more than 90% of patients. It has a propensity to follow dissemination in a well-established pattern. This facilitates the use of localized treatment modalities in its therapeutic approach that include surgery and radiotherapy. Advanced stage presentations occur in less than 30% of patients, and the skin is only rarely affected. Isolated case reports of CHL affecting the skin have been described. However, CHL can have other cutaneous manifestations that may not be directly attributed to the dissemination of the disease. Here we report the coexistence of CHL and malignant melanoma as the presentation of papules and a plaque, in an individual with remote history of CHL. This is the first report of the simultaneous existence of both disorders.

Case presentation

A 62 year-old man presented with 3-4 months history of two pink-papules on the scalp, and a pink crusted plaque on the left neck. He had a previous remote history of nodular sclerosis classical Hodgkin lymphoma and therapy related acute myeloid leukemia with monosomy 7. His lymphoma was under control after the chemotherapy, but he did had bone marrow extension at the time of diagnosis. A hematopoietic allogeneic transplant was done after his original diagnosis of acute myeloid leukemia. Two punch biopsies were obtained. The biopsy from the left neck ( Figure 1) showed a mixed dermal inflammatory infiltrate with scattered atypical large multinucleated and mononuclear cells, intermixed with aggregates of neutrophils, small lymphocytes and histiocytes. The mononuclear cells had hyperchromatic nuclei with vesicular smudged chromatin and prominent cherry red nucleoli, resembling Reed-Sternberg cells. By immunohistochemistry (Figure 2), the atypical cells were positive for CD30, CD20, CD79a, and had dim CD15 and PAX5 staining. They were negative for CD45. A CD3 and CD43 highlighted the abundant intermixed T-cells, but were negative among the atypical large cells. CD68 stained a rich histiocytic background. A Melan-A and S100 stains were also negative. In-situ hybridization for EBV was negative as well.

The two biopsies from the scalp ( Figure 3) show an atypical melanocytic proliferation, with features most compatible with malignant melanoma, largely involving the dermis. There were large nests of atypical melanocytes with light eosinophilic cytoplasm, hyperchromatic and vesicular nuclei with variable prominent nucleoli. Scattered mitotic figures were seen, including in the deeper portion of the lesion. No maturation towards the base of the lesion was seen. An intraepidermal melanocytic component was present in one of the biopsies. No perineural or lymphovascular space invasion was identified. Immunohistochemistry for Melan-A and HMB-45 confirmed the melanocytic origin of the tumor cells.

Discussion

Hodgkin lymphoma (HL) is a disease of young adults (12% of all lymphomas) and elderly people, and is composed of two separate entities: classical HL (95% of cases) and nodular lymphocytic predominant HL (5% of cases) [1]. First described by the German physician Grosz in 1906, cutaneous Hodgkin lymphoma (CHL), an exceedingly rare manifestation of the disease (0.5 -7.5 %), occurs when the Figure 1 Punch biopsy from the left neck with involvement by HL. 1a and 1b: Hemotoxylin and Eosin stain (20× and 100×). There is an atypical infiltrate involving the entire dermis with scattered larger cells. A grenz-zone is between the infiltrate and the epidermis. 1c -1f: Hemotoxylin and Eosin stain (200× and 400×). The infiltrate is composed predominantly of small lymphocytes and abundant histiocytes in the background. Several large cells, some of which are binucleated and show prominent nucleoli (compatible with Reed-Sternberg cells and RS variants) are seen. In addition, scattered neutrophils are also present. Atypical mitoses can be easily detected.

malignant cells invade the dermis [2]. Nonetheless, cutaneous symptoms can be seen in up to 40% of patients with HL [3]. The current WHO-EORTC classification identifies cutaneous HL as a secondary systemic dissemination of the disease [1,4]. large, hyperchromatic, irregular shaped nuclei are easily identifiable. The Reed-Sternberg cells are admixed predominantly with plasma cells and lymphocytes with occasional histiocytes and eosinophils. Necrosis is generally absent. The epidermis is spared in most of the cases [2][3][4][5]. In this particular case, the patient had a remote history of nodular sclerosis classical Hodgkin lymphoma that preceded the secondary involvement of the skin by many years (10-15 years). Although his original biopsy slides were not available for review, the histologic features seen on the diagnostic skin biopsy were more suggestive of a mixed cellularity variant of CHL: there was an abundance of mixed inflammatory cells that included neutrophils, histiocytes, plasma cells, lymphocytes, and rare eosinophils without significant fibrosis. The population of RS cells and variants was significant as it is depicted on the Figure 1.

Based on morphology alone, it is almost impossible to distinguish CHL with abundant numbers of neoplastic cells from other primary cutaneous lymphoproliferative disorders, such as CD30+ lymphoproliferative disorder (lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large-cell lymphoma (ALCL)), or even tumor stage mycosis fungoides when the epidermotropism is minimal. Other reactive CD30+ processes including: pseudolymphomatous drug reactions, nodular scabies, atopic dermatitis, and infections can also be in the differential diagnosis [4]. and CD15 for the majority (75-85%) of cases and are usually negative for CD45, CD20, ALK and EMA. However, up to 20-30% of CHL can be positive for CD20, and its positivity is a marker of better prognosis, and response to rituximab. The B-cell nature of Reed-Sternberg cells is shown by the B-cell specific activator protein (BSAP), product of the PAX-5 gene in approximately 90% of cases. Additionally the tumor cells can be positive for EBER, by in-situ hybridization [1,5,6]. Other immunohistochemical markers that have some utility are OCT-2 and BOB-1, which are positive (not both) in up to 90% of cases [1]. In contrast, LyP, c-ALCL, or transformed MF show invariable negative expression of CD15 or Pax-5 [4,6].

A systemic B-cell lymphoma that can sometimes enter in the differential diagnosis is T-cell histiocyte-rich large B-cell lymphoma (THRLBCL). But in THCRLBCL there is strong expression of CD45, CD20, CD79a and PAX-5. The current case showed a typical CHL immunophenotype with CD30 and CD15 expression, but negative for CD45. An unusual phenotype with CD20 and CD79a expression was also seen, but PAX5 showed the classic dim staining characteristic of CHL. EBER was negative, a feature commonly seen in most cases of nodular sclerosis and mixed cellularity CHL. The mode of HL spread to the skin has been explained by three mechanisms: (1)retrograde lymphatic spread, distal to the tumor involved regional lymph node(s), which is the most common; (2)direct extension from an underlying nodal focus; and (3) hematogenous dissemination where no tumor-involved lymph nodes are identified in the immediate vicinity of the involved skin [3,4].

The coexistence of different malignancies in patients with Hodgkin and NHL has been previously documented: Yang et al. [7] reported a patient with nodal angioimmunoblastic T-cell lymphoma (AITCL) who had a partial response to chemotherapy, and developed an EBV-associated cutaneous diffuse large B-cell lymphoma few months after his original diagnosis of AITCL. El Demellawy et al. [8] reported a synchronous collision tumor of malignant melanoma and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). We have also seen in our personal experience the coexistence of CLL/SLL with melanoma and squamous cell carcinoma.

Concurrent malignant melanoma and lymphoma occurs in 0.3% of patients with melanoma [9]. Since 1960, a rising incidence of melanoma and NHL has been observed, probably related to UV exposure and immunosupression (such as cases presenting in individuals who are stem cell transplant recipients and patients with AIDS) [9,10]. Adami et al. [10] first reported a link between NHL, CLL/SLL and skin cancer (the relative risk of developing melanoma was 2.4 among NHL patients) and suggested that UV light may contribute to increasing incidence of NHL. Riou et al. [11] reported a 16 fold higher incidence of lymphomas in patients with malignant melanoma. A recent study also found a 3.5 to 7.5 fold increase of NHL in patients with melanoma [9]. Alterations of p16 pathway, which inhibit CDNK4, a tumor suppressor gene, are common in both types of malignancies [5,9].

More interestingly, the development of skin cancers after non-myeloablative allogeneic bone marrow transplants (NMAT) has been well documented. Cavalier et al. [12] reported a series of 6 cases of skin cancers (mostly squamous cell carcinomas, but 2 of the patients had melanoma) in patients with NMAT. The most interesting finding in their study was a particular strong association of skin cancers in those patients who received their transplant for myelodysplasia or acute myeloid leukemia. In this case the patient developed a therepy related myeloid neoplasm subsequent to the chemotherapy for CHL. The mechanism implicated in the development of skin cancers is the immunosupression from the induction chemotherapeutic regimens that are administered prior to the transplant. In particular, the depletion of CD4+ lymphocytes is a well known predisposer for skin cancers. Patients who have an aggressive myeloid neoplasm usually receive more intensive induction regimens, a fact that creates a more immunosuppressive background. Ultimately, fludarabine, a purine analogue that is typically use in induction chemotherapy, results in DNA inactivation and apoptosis. Fludarabine also inhibits DNA-polymerase, RNA-polymerase, DNA-ligase, DNA-primase and ribonucleotide reductase [13]. Fludarabine also depletes CD3, CD4 and CD8 lymphocytes over a period of a month. In this case fludarabine was one of the drugs administered prior to his transplant. Additional possible mechanisms which are linked to carcinogenesis include p53 mutations and HPV infection (in squamous cell carcinomas).

In the past, 3 cases of patients with melanoma developed Hodgkin's disease thereafter and were published in the literature [7,9]. However, concurrent cutaneous involvement by HL and melanoma has never been reported. Causality between both malignancies remains to be established. Our case illustrates the first case report of malignant melanoma and CHL in a patient presenting simultaneously.

Figure 2
2Cutaneous manifestation of HL show different clinical features: (a) papules, (b) plaques, (c) nodules or tumors, (d) ulcerative lesions, (e) various combinations of these features and (f) erythroderma [2]. It is usually centered in the reticular dermis and commonly extends into the subcutaneous fat. The tumor shows nodular or interstitial growth pattern with adnexal involvement. Various forms of Reed-Sternberg cells with Immunohistochemistry of the punch biopsy from the left neck. The atypical cells are positive for CD30, CD79a and CD20. CD15 and PAX5 show positive and dim staining in the tumor cells. CD3 and CD68 (not shown) stain a background of small T-cells and abundant histiocytes, respectively. The large cells are negative for CD45, EBER and Melan-A (not shown).

Figure 3
3By immunohistochemistry, the neoplastic cells in Classical HL are positive for CD30 in nearly all cases Punch biopsy from the scalp with malignant melanoma. 3a and 3b: Hemotoxylin and Eosin stain (20× and 100×). There is an atypical melanocytic proliferation with a predominant dermal component, but with individual atypical junctional nests seen. 3c and 3d: Hemotoxylin and Eosin stain (200× and 400×). The atypical melanocytes are predominantly epithelioid with light eosinophilic cytoplasm, hyperchromatic and vesicular nuclei with variable prominent nucleoli. Scattered mitotic figures were seen, including in the deeper portion of the lesion. 3e and 3f: Melan-A immunostain (20× and 100×).
http://www.diagnosticpathology.org/content/8/1/135
ConsentAn attempt to obtain informed consent was performed. However, this patient has been lost to follow up, and no close family members were available (based on the provided demographic information) to obtain informed consent from.Competing interestsThe authors don't have any conflict of interest to disclose.Authors' contributions AAG wrote the manuscript, took the clinical pictures, obtain the references, was responsible for the additional work-up performed after the manuscript acceptance, and also edited it. DL was the main pathologist who had the case and review the manuscript and performed additional editing. All authors read and approved the final manuscript.
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Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color figure charges • Immediate publication on acceptance • Inclusion in PubMed, CAS, Scopus and Google Scholar • Research which is freely available for redistribution. Lu Gru, Diagnostic Pathology. 8135Concurrent malignant melanoma and cutaneous involvement by classical hodgkin lymphoma (CHL) in a 63 year-old man. Submit your manuscript at www.biomedcentral.com/submitCite this article as: Gru and Lu: Concurrent malignant melanoma and cutaneous involvement by classical hodgkin lymphoma (CHL) in a 63 year-old man. Diagnostic Pathology 2013 8:135. Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color figure charges • Immediate publication on acceptance • Inclusion in PubMed, CAS, Scopus and Google Scholar • Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit