Qin He

Novel homozygous nonsense TMC8 mutation detected in patients with epidermodysplasia verruciformis from a Brazilian family

1 Bondeson J, Maini RN. Tumour necrosis factor as a therapeutic target in rheumatoid arthritis and other chronic inflammatory diseases: the clinical experience with infliximab (Remicade). Int J Clin Pract 2001; 55:211–16. 2 Reich K, Nestle FO, Papp K. EXPRESS study investigators. Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicentre, double-blind trial. Lancet 2005; 366:1367–74. 3 O’Quinn RP, Miller JL. The effectiveness of tumor necrosis factor alpha antibody (infliximab) in treating recalcitrant psoriasis. Arch Dermatol 2002; 138:644–8. 4 Rongioletti F, Borenstein M, Kirsner R, Kerdel F. Erythrodermic, recalcitrant psoriasis: clinical resolution with infliximab. J Dermatol Treat 2003; 14:222–5. 5 Fiehn C, Andrassy K. Hitting three with one strike: rapid improvement of psoriatic arthritis, psoriatic erythroderma, and secondary renal amyloidosis by treatment with infliximab (Remicade). Ann Rheum Dis 2004; 63:232. 6 Lisby S, Gniadecki R. Infliximab (Remicade) for acute, severe pustular and erythrodermic psoriasis. Acta Derm Venereol (Stockh) 2004; 84:247–8. 7 Castro LGM, Muniz M, Takahashi MDF. Infliximab induces rapid remission of erythrodermic psoriasis. J Eur Acad Dermatol Venereol 2005; 19(Suppl. 2):FC07.11. 8 Heikkilä H, Ranki A, Cajanus S, Karvonen SL. Infliximab combined with methotrexate as long-term treatment for erythrodermic psoriasis. Arch Dermatol 2005; 141:1607–10. 9 Valdés MP, Schroeder F, Roizen V et al. Eficacia y seguimiento en el largo plazo de pacientes con psoriasis vulgar moderada a severa en tratamiento con infliximab (Remicade ). Rev Med Chile 2006; 134:326–31. 10 Mahé E, Descamps V, Grossin M et al. CD30+ T-cell lymphoma in a patient with psoriasis treated with ciclosporin and infliximab. Br J Dermatol 2003; 149:170–3.

Contribution of beta-HPV infection and UV damage to rapid-onset cutaneous squamous cell carcinoma during BRAF-inhibition therapy

Purpose: BRAF-inhibition (BRAFi) therapy for advanced melanoma carries a high rate of secondary cutaneous squamous cell carcinoma (cSCC) and risk of other cancers. UV radiation and α-genus human papillomavirus (HPV) are highly associated with SCC, but a novel role for β-genus HPV is suspected in BRAFi-cSCC. Cutaneous β-HPV may act in concert with host and environmental factors in BRAFi-cSCC. Experimental Design: Primary BRAFi-cSCC tissue DNA isolated from patients receiving vemurafenib or dabrafenib from two cancer centers was analyzed for the presence of cutaneous oncogenic viruses and host genetic mutations. Diagnostic specimens underwent consensus dermatopathology review. Clinical parameters for UV exposure and disease course were statistically analyzed in conjunction with histopathology. Results: Twenty-nine patients contributed 69 BRAFi-cSCC lesions. BRAFi-cSCC had wart-like features (BRAFi-cSCC-WF) in 22% of specimens. During vemurafenib therapy, BRAFi-cSCC-WF arose 11.6 weeks more rapidly than conventional cSCC when controlled for gender and UV exposure (P value = 0.03). Among all BRAFi-cSCC, β-genus HPV-17, HPV-38, HPV-111 were most frequently isolated, and novel β-HPV genotypes were discovered (CTR, CRT-11, CRT-22). Sequencing revealed 63% of evaluated BRAFi-cSCCs harbored RAS mutations with PIK3CA, CKIT, ALK, and EGFR mutations also detected. Conclusions: We examined clinical, histopathologic, viral, and genetic parameters in BRAFi-cSCC demonstrating rapid onset; wart-like histomorphology; β-HPV-17, HPV-38, and HPV-111 infection; UV damage; and novel ALK and CKIT mutations. Discovered β-HPV genotypes expand the spectrum of tumor-associated viruses. These findings enhance our understanding of factors cooperating with BRAF inhibition that accelerate keratinocyte oncogenesis as well as broaden the knowledge base of multifactorial mediators of cancer in general. Clin Cancer Res; 21(11); 2624–34. ©2015 AACR.

Detection of high‐risk human papillomaviruses in verrucae of patients with mycosis fungoides and Sézary syndrome: a case series

Background  Mycosis fungoides (MF)/Sézary syndrome (SS) patients are immunocompromised and thus may be susceptible to high‐risk human papillomavirus (HPV) infections that are difficult to treat.

Merkel cell polyomavirus DNA detection in a patient with Merkel cell carcinoma and multiple other skin cancers

Further studies have demonstrated thatMCPyV is clonally integrated at various sites in the gen-ome of MCC tumors, with truncating mutations thatinterrupt viral replication; therefore, demonstrating thatthe virus is not a passenger virus that secondarily infectsMCC tumors, but is an etiological agent.

Coincidental consort clear cell cutaneous carcinoma: facial squamous cell carcinoma in situ containing human papillomavirus and cancer cells with clear cytoplasm in an octogenarian couple.

Clear cell squamous cell carcinoma in situ, also referred to as pagetoid or clear cell Bowen disease, is a rare pathologic variant of this neoplasm. It is characterized by neoplastic cells with clear or pale cytoplasm. An octogenarian husband and wife concurrently developed new facial skin lesions which demonstrated squamous cell carcinoma in situ consisting of cancer cells with clear cytoplasm. Cutaneous human papillomavirus (HPV) typing detected HPV Type 5 and HPV Type 21 in the tumors of the husband and wife, respectively. HPV is a potential etiologic factor in the oncogenesis of nonmelanoma skin cancer, and HPV DNA has been demonstrated in extragenital squamous cell carcinoma in situ. The detection of DNA from different HPV types in the tumors of our patients suggests that the concurrent occurrence of their skin cancers may have been coincidental. However, the presence of HPV DNA in their tumors introduces the possibility of a viral-associated oncogenesis for clear cell squamous cell carcinoma in situ.

Beta Human Papillomavirus Infection Is Prevalent in Elephantiasis and Exhibits a Productive Phenotype: A Case-control Study

Abstract: Elephantiasis is considered a cutaneous region of immune deficiency with cobblestone-like surface caused by a wart-like eruption. Verrucosis is a diffuse human papillomavirus (HPV) infection linked to immunodeficiency disorders. The objective of this study was to examine the prevalence of HPV infection in lymphedema and its pathogenic role in elephantiasis. A retrospective case-control study was performed examining lymphedematous skin and controls of peritumoral normal skin. HPV infection was evaluated at the DNA, protein, and histopathologic levels by polymerase chain reaction, immunohistochemistry, and light microscopy, respectively. Overall, 540 HPV DNAs were detected in 120 of 122 cutaneous samples (median 4 HPV DNAs per sample, range 0–9). Compared with controls, no differences existed in type or number of HPVs identified. Instead, a diverse spectrum of HPV-related histopathologies were evident, likely reflecting the multiplicity of HPV genotypes detected. Most notably, increasing histopathologic lymphedema stage significantly correlated with markers of productive HPV infection such as altered keratohyaline granules and HPV L1 capsid expression. Limitations of this study are the absence of normal skin controls not associated with neoplasia or subclinical lymphedema, and lack of assessment of HPV copy number per keratinocyte infected. In conclusion, productive HPV infection, not HPV type or numbers detected, distinguished lymphedematous skin from controls. These findings support the theory that lymphedema creates a region of depressed immunity that permits productive HPV infection, manifested clinically by diffuse papillomatosis, characteristic of elephantiasis.

Detection of human papillomavirus in cutaneous clear cell squamous cell carcinoma in situ: viral-associated oncogenesis may contribute to the development of this pathologic variant of skin cancer

To the Editor, We read with interest the excellent study by AlArashi and Byers which adds to the clinical, morphological, histological and immunohistochemical characteristics of clear cell squamous cell carcinoma in situ (SCCIS) and clear cell change in SCCIS. Their findings support outer root sheath differentiation in these tumors. Our recent detection of human papillomavirus (HPV) in clear cell SCCIS adds further to the characterization of this tumor and suggests that a viral-associated oncogenesis may contribute to the development of this pathologic variant of skin cancer. We evaluated and treated new tumors that had concurrently developed on the faces of an octogenarian husband and wife. The discovery that both cancers were the rare clear cell variant of SCCIS and that both tumors were located on exposed skin of potential contact between the spouses prompted us to consider the possibility that the cancers had a viral-induced etiology and that one spouse may have acquired the tumor-associated virus from the other partner. Cutaneous HPV typing by polymerase chain reaction and sequencing confirmed the presence of HPV in both tumors. However, HPV type 5 was detected in the husband’s clear cell SCCIS and HPV type 21 was detected in the wife’s tumor. Therefore, in summary, although our findings did not show contact transmission of a single tumorassociated etiologic virus, they did confirm the presence of HPV DNA in the clear cell SCCIS from both spouses. We consider it unlikely that the detection of HPV DNA in both of our immunocompetent patient’s clear cell SCCIS merely represents the coincidental ubiquitous presence of viral DNA in the tumor-containing (lesional) skin and normal appearing (nonlesional) adjacent skin. However, we cannot exclude this possibility with absolute certainty because we were not able to evaluate the normal appearing skin adjacent to our patients’ tumors for the presence of commensal, subclinical, skin HPV infection. A viral etiology may be a factor in the cutaneous oncogenesis of nonmelanoma skin cancer. Indeed, HPV has been identified in squamous cell carcinomas from both immunosuppressed patients and immunocompetent individuals. The detection of HPV types in the clear cell SCCIS from two people raises the possibility that this unusual variant of SCCIS is associated with an infectious etiology. If the presence of HPV DNA can be confirmed in additional clear cell SCCIS, it would support the hypothesis that a viral-associated oncogenesis plays a role in the induction of this pathologic variant of skin cancer.

Distinct gene expression profiles in two cases of Merkel cell polyomavirus‐negative Merkel cell carcinoma: shedding light on an esoteric entity

development of keratin squames, and the retention of melanin in certain areas of the skin. Accumulation of the residues of sweat, scales, sebum, emollients, bath oils, and soaps may also contribute to its pathogenesis. The condition usually manifests as asymptomatic, dirtlike, slightly papillomatous, hyperpigmented patches or plaques primarily on the neck and trunk. It can be seen at any age and in both genders. Lesions are resistant to regular washing with soap but are easily removed by wiping with ethyl or isopropyl alcohol. Cases of TFFD can be both diagnosed and treated using this simple procedure. Recurrence is unusual after treatment. Differential diagnoses include dermatosis neglecta (DN), confluent and reticulate papillomatosus of Gougerot and Carteaud, pityriasis versicolor, and acanthosis nigricans. Whether TFFD and DN are different diseases or diverse types of the same disease is still controversial. In DN, the patient neglects to wash the lesion for any of a number of different reasons, the most common of which is poor hygiene. Both TFFD and DN lesions can be treated completely by wiping with alcohol; however, DN lesions can also be cleared by washing with soap and water. The lesions of any of the other disorders included within the gamut of the differential diagnosis cannot be cleared by wiping with alcohol or by washing. Although both of our patients had regular washing habits, their lesions were gradually growing. We were able to remove the lesions easily with alcohol. To the best of our knowledge, only approximately 60 cases of TFFD have been reported in the literature until now. Lack of awareness of this condition, even among dermatologists, is likely to be the major reason for the under-reporting of the entity. Unnecessary skin biopsies and batteries of blood tests can be avoided if TFFD is retained in the differential diagnosis of such presentations.

Human papillomavirus type 73 associated with multiple cutaneous squamous cell carcinomas in an immunosuppressed patient

Our patient was a 43-year-old HIV-positive man, on antiretrovirals with an undetectable viral load and a CD4 count of 80 cells/mm, chronic obstructive pulmonary disease, hemodialysis-dependent renal failure, 15 years of intermittent condyloma accuminata, and periungual verruca vulgaris. His skin was Fitzpatrick Type II, and he had no family history of non-melanoma skin cancer. He presented to our clinic with three years of perianal and penile verrucous plaques, and similar lesions covering his left thumb and the fingerpad and periungual area of his left first finger (Figs. 1 and 2). Histopathology of the perianal lesions demonstrated condyloma, and the lesions on the thumb and finger demonstrated squamous cell carcinoma (SCC) in situ, invasion not excluded (Fig. 3). Human papillomavirus (HPV) detection was performed by polymerase chain reaction (PCR) using the GP primer system. The typing was determined by the cloning, sequencing, and computer analysis of the obtained HPVPCR product. The condyloma was positive for HPV 11, while the SCCs of the finger and thumb were positive for HPV 73. The condyloma was treated with shave removal and electrocauterization followed by imiquimod 5% cream three times per week for three weeks, and the genital area remained clear at one year. Because of the extensive disease of the thumb and finger and the patient’s preference, he underwent amputation of the thumb and the distal phalanx of the finger. Pathological specimens demonstrated extensive SCC in situ with clear margins. Eight months following surgery, the patient presented with verrucous papules at the amputation site on the 713