Erythema gyratum repens associated with pityriasis rubra pilaris

Erythema gyratum repens (EGR) is a rare cutaneous eruption characterized by serpiginous morphology and a migrating scaly border. It is one of the most specific cutaneous paraneoplastic phenomena, and is associated with malignancy in most cases. We report a 46‐year‐old Afro‐Caribbean man with the unequivocal clinical and histological features of pityriasis rubra pilaris (PRP). However, despite improvement on oral acitretin, the morphology of the eruption evolved into the striking serpiginous rash of EGR. The histology findings, although nonspecific, were in keeping with the diagnosis of EGR. No evidence of malignancy was found. Only four cases of PRP evolving into EGR have been reported in the literature, and none was associated with malignancy. All previously reported cases of EGR have been described in white patients, making our case the first reported exception, to our knowledge. The possible role of retinoids in altering the rash of PRP to that of EGR is discussed.     

Paraneoplastic pityriasis rubra pilaris in association with bronchogenic carcinoma

Pityriasis rubra pilaris (PRP) is an uncommon dermatosis occasionally reported in association with an underlying malignancy. We report a 61-year-old woman in whom PRP preceded the diagnosis of bronchogenic carcinoma by approximately 11 months. The clinical picture in this case included atypical cutaneous signs and mucous membrane involvement. Curative treatment of the malignancy with radiotherapy led to resolution of the mucocutaneous changes within months. A presentation of PRP, particularly if atypical, or in an older patient, should prompt consideration of an associated internal malignancy.     

Retroperitoneal undifferentiated pleomorphic sarcoma having microsatellite instability associated with Muir‐Torre syndrome: case report and review of literature

Muir‐Torre syndrome represents a rare autosomal dominant familial cancer predisposition disorder defined by the occurrence of cutaneous sebaceous tumors and an internal malignancy, most commonly gastrointestinal carcinoma. Most examples of hereditary non‐polyposis cancer syndrome (Lynch syndrome), including the Muir‐Torre syndrome, are associated with microsatellite instability (MSI) and germline mutations in mismatch repair genes—most commonly MLH1 or MSH2. We present a 58‐year‐old man with Muir‐Torre syndrome and a large retroperitoneal mass (14.3 cm in greatest dimension) encompassing the left adrenal gland. Sections showed a cellular malignant tumor composed of spindle cells with a high mitotic index and lacking morphologic evidence of adipocytic differentiation. It was weakly reactive for smooth muscle actin (SMA) and negative for desmin, CD117, CD31, CD34, S100 protein and pan‐cytokeratin. Further immunohistochemical analysis revealed intact expression of MLH1 but loss of MSH2 in tumor nuclei. Compared to non‐neoplastic tissue, the tumor showed MSI in five of seven dinucleotide markers. Fluorescence in situ hybridization (FISH) failed to reveal 12q15 amplification, effectively excluding dedifferentiated liposarcoma as a diagnostic consideration. This is a rare case of a patient with Muir‐Torre syndrome who developed a related high‐grade undifferentiated pleomorphic sarcoma as the associated internal malignancy.     

Pityriasis rubra pilaris as the initial manifestation of internal neoplasia

Pityriasis rubra pilaris (PRP) is a rare papulosquamous disorder of unknown aetiology. There are only three cases reported occurring coincident with internal neoplasia We report a case of this disorder presenting as the initial manifestation of a previously undiagnosed malignancy with metastases in the liver. The primary tumour was not detected. The patient had a complete remission of his PRP with topical steroids alone, but died of the malignancy.     

Paraneoplastic pityriasis rubra pilaris: case report and literature review

Pityriasis rubra pilaris (PRP; MIM 173200) is an uncommon papulosquamous inflammatory dermatosis. Only a few cases of PRP associated with an underlying malignancy have been documented. We investigated a 59‐year‐old patient presenting with a fulminant form of PRP recalcitrant to systemic retinoid therapy, in whom the skin disease heralded a diagnosis of cholangiocarcinoma. We searched the MEDLINE database to find articles reporting on similar associations of PRP with malignancies. We identified 10 studies linking PRP and malignancies, but an association between PRP and cholangiocarcinoma has not yet been reported.     

Pityriasis rubra pilaris – a retrospective single center analysis over eight years

Background: Pityriasis rubra pilaris (PRP) is a rare papulosquamous dermatosis. We evaluated evaluate co‐morbidities, complications, and outcome of treatment regimens. Patients and Methods: This is a retrospective study at an academic teaching hospital. We analyzed all patients with the definite diagnosis of PRP seen since 2001. Epidemiologic data, co‐morbidities, response to and course during treatment were investigated. Results: We identified 10 PRP‐patients (6 men, 4 women), mean age 56.4 years, with type I (n = 9) and type IV (n = 1). Three patients had internal co‐morbidities (atrial fibrillation with cardiac insufficiency, dilated cardiomyopathy, diabetes mellitus). Two patients needed psychiatric treatment because of depression. PRP caused ectropium (2 ×), diffuse effluvium (1 ×), and stenosis of the outer ear canal (1 ×). We did not observe a spontaneous remission. Among 9 patients with PRP type I, five were treated with acitretin (two of them as Re‐PUVA), and two with methotrexate (in one patient combined with fumaric acids). Systemic corticosteroids were not effective. One patient was treated with infliximab i.v., 5 mg/kg body weight. Starting with the first application, inflammatory activity decreased and erythema got paler. The treatment was well tolerated. Conclusions: PRP type I is a severe, chronic inflammatory dermatosis responding hesitantly to classic systemic therapies. Tumor necrosis factor‐α antagonists are an effective treatment option for difficult cases.     

Primary signet‐ring cell carcinoma of the axilla

Primary cutaneous histiocytoid or signet‐ring cell carcinoma represents an extremely rare adnexal neoplasm that most frequently presents on the eyelid but more rarely may present in the axilla. As this tumor can resemble metastatic carcinoma with signet‐ring cells, especially lobular carcinoma of the breast, it can often present a diagnostic challenge. We present a case of cutaneous signet‐ring cell carcinoma presenting in the axilla and outline the challenges of diagnosing this rare malignancy.     

Ustekinumab treatment of pityriasis rubra pilaris: A report of five cases

Pityriasis rubra pilaris (PRP) is a rare, chronic, inflammatory skin disease of unknown etiology. Patients refractory to conventional therapies have been treated successfully with biologic drugs such as anti‐tumor necrosis factor agents. Recently, a role of the interleukin‐23/T‐helper 17 axis in PRP has been described. Our objective was to assess the effectiveness of ustekinumab in five patients with adult‐onset PRP refractory to conventional therapies. In the present study, four patients had type I and one patient type II adult‐onset PRP. They were treated with three s.c. doses of ustekinumab at weeks 0, 4 and 16. Clinical response was evaluated monthly during treatment up to a 15‐month follow‐up period. All patients promptly showed a decrease in erythema, follicular hyperkeratosis and scaling. After three injections, complete remission of skin lesions was achieved in four out of five cases and a significant clinical improvement was shown in one case. To the best of our knowledge, this is the largest case series reported on ustekinumab treatment in PRP. Our results, in addition to previous studies from other groups, suggest that ustekinumab may be a possible first‐line treatment for PRP patients refractory to conventional therapies.     

CARD14 Glu138 mutation in familial pityriasis rubra pilaris does not warrant differentiation from familial psoriasis

Some familial cases of pityriasis rubra pilaris (PRP) have the CARD14 gene mutations that are also detected in familial psoriasis vulgaris. However, genotype–phenotype correlation in these two entities is poorly understood. Here, we report a case of PRP with a new mutation in CARD14. Genomic analysis of a 40‐year‐old female patient with sporadic PRP type V identified a heterozygous dominant c.412G>A mutation (p.Glu138Lys) in CARD14. Two types of CARD14 mutations causing Glu138 substitutions have been reported in cases of familial PRP and pustular psoriasis. All three types, including the present case, are predicted to cause similar loss of the negative charges at this site. This suggests that the difference in molecular charge and the resulting change in molecular interaction around the N‐terminal end of the coiled‐coil region of CARD14 molecule do not determine the phenotypic differences between psoriasis and PRP.     

Cases with a spontaneous regression of an infiltrating non‐crateriform keratoacanthoma and squamous cell carcinoma with a keratoacanthoma‐like component

We herein report the natural course of an early/proliferative stage keratoacanthoma (KA) with infiltrating islands of cytological malignancy (case 1) and a squamous cell carcinoma (SCC) with a KA‐like component (case 2), which were observed until their complete regression. The presented case 1 suggests that one of the histopathological forms of KA includes this unusual, infiltrating, non‐crateriform architecture, and also indicates the possibility of complete remission in the KA associated with infiltrating islands of cytological malignancy. In the presented case 2, the peripherally‐associated KA‐like focus was histopathologically considered to be either a remnant of KA focus or verrucous keratosis (hyperplasia). Therefore, the complete spontaneous regression of case 2 suggests that SCC arising in KA still has the potential of spontaneous regression, or that an extremely rare event, namely, the spontaneous regression of (traditional) SCC occurred in the present case.     

Photodynamic therapy efficiently controls dermatophytosis caused by Trichophyton rubrum in a murine model

Hydroa vacciniforme (HV) is a rare photodermatosis that mainly affects children and manifests as vesiculopapular eruptions in sun‐exposed areas without systemic symptoms. HV‐like lymphoma (HVLL) is one of the Epstein–Barr virus (EBV)‐associated lymphoproliferative disorders (LPD) of childhood. Its diagnosis is based on monoclonal T‐cell proliferation; however, its degree of malignancy is controversial owing to its variable prognosis. Elderly‐onset cases of these diseases are extremely rare, and the clinical features remain unknown. It has been shown that late onset is closely associated with a severe phenotype in EBV‐associated LPD including atypical HV. Here we describe a case of elderly‐onset atypical HV accompanied by T‐cell monoclonality, but with a very indolent clinical course. Our patient indicates a possible case with elderly‐onset atypical HV manifesting a favourable course, and that T‐cell monoclonality and age of onset cannot always predict the disease severity, and highlights the difficulty of prognosis prediction in elderly‐onset atypical HV.     

Case of pityriasis rubra pilaris progressed to generalized erythroderma following blockade of interleukin‐17A,but improved after blockade of interleukin‐12/23 p40

We report herein a case of a 72‐year‐old man with pityriasis rubra pilaris (PRP) that was refractory to conventional therapies. His skin lesions progressed to generalized erythroderma despite anti‐interleukin (IL)‐17A antibody therapy. Topical corticosteroids, emollients, systemic retinoid, methotrexate, cyclosporin and phototherapy yielded no therapeutic response. However, blockade of IL‐12/23 p40 dramatically improved his cutaneous lesions. Complete remission was achieved 4 weeks after the first injection of ustekinumab and maintained for more than 48 weeks. Our data indicate that IL‐12 was associated with the onset of PRP in this patient, rather than IL‐23. IL‐12 is critical for the differentiation of T‐helper (Th)1 cells. Thus, the Th1 pathway may be associated with the onset of PRP.     

High‐risk human papillomavirus in a child with digital pigmented Bowen's disease: Case report and dermoscopic findings

Squamous cell carcinoma in situ, also known as Bowen's disease (BD), is a skin malignancy most commonly seen in middle‐aged and elderly adults. Pediatric BD is rare and can be a diagnostic challenge for physicians. Digital BD has largely been associated with human papilloma virus. We report an immunocompetent 11‐year‐old girl with periungual pigmented BD induced by high‐risk human papilloma virus.     

Nonmelanoma skin cancer after renal transplantation: a single-center experience in 1736 transplantations

Background Renal transplantation is associated with an increased incidence of nonmela‐noma skin cancer (NMSC) caused by immunosuppression. Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), the two major histological types of NMSC, exhibit more aggressive biological and clinical courses in renal transplant recipients (RTRs), with higher rates of recurrence and mortality than in the general population. Methods We retrospectively analyzed our experience of NMSC in 1736 renal transplantations performed over a 25‐year period. All cases of skin cancer after renal transplantation were included except those of skin cancer resulting from melanoma and mesenchymal skin tumors. Results In our series, the overall incidence of NMSC after transplantation was 2.2% (n = 39), and SCC represented the most frequent skin malignancy (64.1%), followed by BCC (17.9%), Bowen’s disease (10.2%), basosquamous carcinoma (5.1%), and a rare case of invasive sebaceous carcinoma (2.6%). A shift to newer immunosuppressive regimens after the initial diagnosis of NMSC had been implemented in eight cases (20.5%). The recurrence rate after initial treatment was 41% (n = 16), and distant metastatic disease was diagnosed in 15.4% (n = 6) of NMSC patients. The NMSC‐specific mortality rate was 25.6% (n = 10). Conclusions Nonmelanoma skin cancer remains a significant source of morbidity and mortality in RTRs, and post‐transplant surveillance should be increased.     

Treatment of refractory adult‐onset pityriasis rubra pilaris with TNF‐alpha antagonists: a case series

Background Pityriasis rubra pilaris (PRP) is a rare inflammatory dermatosis with frequent clinical presentation as erythroderma. Conventional systemic treatment is often unsatisfactory and limited by long‐term toxicity. The use of tumour necrosis factor (TNF) antagonists has been reported previously in single cases, but lacking long‐term follow‐up or comparison between different biological agents. Objectives To assess the long‐term efficacy and safety of TNF‐alpha antagonist, infliximab and etanercept, either in monotherapy or in combination therapy of severe, refractory adult‐onset PRP. Methods Seven patients of adult‐onset PRP, six newly diagnosed type‐I and 1 type‐II, which were resistant or ineligible to conventional systemic treatment, received a single course of infliximab or etanercept therapy, alone or in combination with low‐dose acitretin (>0.25 mg/kg/daily). After complete remission and treatment discontinuation, a follow‐up period of 12 months was evaluated for relapses. Results Six patients obtained complete remission after a single course of anti‐TNF‐alpha therapy: mean therapy duration was 19.3 weeks (range 6–48 weeks). All patients obtained significant clearing (>75% of body surface area) of skin lesions at week 12. Two patients with marked keratoderma developed localized disease recurrence during treatment. During follow‐up, only a single patient, affected by type II PRP, had disease relapse. Conclusions Both TNF‐alpha antagonists proved successful for the treatment of refractory, adult‐onset PRP, yielding complete and persistent clinical responses in type‐I PRP. Infliximab was associated with a more rapid onset of action, while treatment duration was comparable with etanercept. PRP type II warranted long‐term therapy and showed relapse after drug discontinuation.     

A case of porocarcinoma arising in pigmented hidroacanthoma simplex with multiple lymph node,liver and bone metastases

Porocarcinoma is a rare skin appendage carcinoma that may arise de novo or be associated with pre‐existing poroma and hidroacanthoma simplex (HAS). Here, we report a case of porocarcinoma arising in pigmented HAS, which led to death from multiple lymph node, liver and bone metastases. A 72‐year‐old Japanese man presented with a brown to focal black flat plaque, measuring 17 × 12 mm, on the posterior region of his right thigh. Histopathological study of the tumor revealed that there was intraepidermal proliferation of small‐sized basaloid cells, and it exhibited the ‘Jadassohn phenomenon’, with dendritic melanocytes, and a few ductal structures were observed. Continuing to the intraepidermal nests, the invasive proliferation of large polygonal cells with occasional intracytoplasmic ductal structures was observed. Carcinoembryonic antigen and epithelial membrane antigen were expressed in some carcinoma cells and they highlighted the intracytoplasmic ductal structures. Multiple lymph node, liver and bone metastases were observed, and the patient died 8 months after the initial surgery. Clinical diagnosis of HAS is extremely rare. Porocarcinoma may be associated with pre‐existing HAS and sometimes shows aggressive behavior. Therefore, pigmented HAS must be included in the differential diagnosis of brown or black lesions. Ishida M, Hotta M, Kushima R, Okabe H. A case of porocarcinoma arising in pigmented hidroacanthoma simplex with multiple lymph node, liver and bone metastases.     

Giant cell angiofibroma or localized periorbital lymphedema?

Giant cell angiofibroma represents a rare soft tissue neoplasm with a predilection for the orbit. We recently encountered a mass removed from the lower eyelid of a 56‐year‐old female that histopathologically resembled giant cell angiofibroma. The process consisted of haphazardly arranged CD34‐positive spindled and multinucleated cells within an edematous, densely vascular stroma. However, the patient had recently undergone laryngectomy and radiotherapy for a laryngeal squamous cell carcinoma. A similar mass had arisen on the contralateral eyelid, and both had developed several months post‐therapy. Lymphedema of the orbit can present as tumor‐like nodules and in some cases may share histopathologic features purported to be characteristic of giant cell angiofibroma. A relationship between giant cell angiofibroma and lymphedema has not been established, but our case suggests there may be one. The potential overlap of these two conditions should be recognized, as should other entities that may enter the differential diagnosis.     

Sebaceous carcinoma within rippled/carcinoid pattern sebaceoma

Although the histogenesis of sebaceous carcinomas remains unclear, the occurrence of intraepidermal or intraepithelial sebaceous carcinoma in the epidermis or conjunctiva may suggest de novo histogenesis. This report describes a case of sebaceous carcinoma within preexisting rippled/carcinoid pattern sebaceoma. This lesion was composed of two (benign and malignant) components, and the benign component of the lesion showed the typical features of a rippled/carcinoid pattern sebaceoma. Although evidence of trauma as well as a vertical orientation was seen in this lesion, the malignant component of the lesion showed histopathological evidence of malignancy (sebaceous carcinoma), such as the aggregations with irregular and infiltrated borders, a sheet‐like growth pattern, and the cytopathological findings of the neoplastic cells, showing a high‐grade of malignancy (a high mitotic index and abnormal mitotic figures). The immunohistochemical staining for p53, Ki‐67 and D2‐40 also favored this diagnosis. This sebaceous carcinoma component was considered to be the incipient stage of carcinoma within preexisting sebaceoma, therefore, it was still considered to be a vertically oriented lesion. This case shows the possibility that abnormal (malignant) sebaceous germinative cells may originate within a sebaceoma, thereby suggesting that some sebaceous carcinomas may develop from preexisting sebaceomas.     

Composite haemangioendothelioma with lymph‐node metastasis: an unusual presentation at an uncommon site

A 48‐year‐old woman presented with red papules on the thigh. Histopathological examination indicated pyogenic granuloma, and the patient was treated with total excision in 2003 and electrocauterization in 2005. Three months later, upon recurrence of the lesions, a diagnosis of composite haemangioendothelioma (CHE) was made. The patient was treated by total excision and lymph‐node dissection, which revealed inguinal lymph‐node metastasis. Despite the surgery, a further local recurrence occurred, subsequently treated by wide excision en bloc, with adjuvant radiotherapy and chemotherapy. Although CHE is defined as a vascular tumour with low‐grade malignancy, the local recurrences and lymph‐node metastases resulted in treatment difficulties in this case. Unlike earlier cases, the tumour in our patient presented as localized numerous small papulonodules, and lymph‐node metastasis was detected within a relatively short time. Dermatologists and pathologists should be aware of this rare condition and include it in the differential diagnosis of vascular lesions.     

Multifocal skin basal cell carcinomata 57 years after topical dry ice treatment

We report a rare case of simultaneous multiple basal cell carcinomata occurring on the back of a patient who had received dry ice treatment to this area almost 6 decades previously. This is also one of the longest recorded disease‐free intervals between skin trauma and basal cell carcinoma development. We discuss the aetiopathology of multiple skin cancers in our patient and the propensity for destructive skin events to predispose to malignancy.