Urticarial lesions in a child with acute lymphoblastic leukemia and eosinophilia

The hypereosinophilic syndrome (HES) is defined by a longer than 6-month history of peripheral blood hypereosinophilia (greater than 1.5 x 10(9)/L), with signs and symptoms of internal organ involvement, in the absence of an identifiable cause. HES is therefore a diagnosis of exclusion. Patients have been reported who initially met the criteria for HES but subsequently developed a rare hematologic malignancy known as acute lymphoblastic leukemia with eosinophilia (ALL-Eo). We report such a case in a 10-year-old boy who presented to the pediatric dermatology clinic with unusual, urticarial skin lesions. Although skin involvement is often reported in cases of HES and ALL-Eo, such findings are variable and reports in the dermatology literature are few. We emphasize the importance of continuous monitoring for underlying malignancy in children with urticarial skin lesions in the setting of unexplained hypereosinophilia.     

Spectrum of cutaneous metastases in 1287 cases of internal malignancies: a study from Turkey

Cutaneous metastases may be either the initial manifestation of an internal malignancy or represent recurrent neoplastic disease. The aim of this study was to investigate the incidence and characteristics of cutaneous metastases in cases of internal malignancy. A total of 1287 patients with internal malignancy were included in the study. Dermatological examinations were performed on all of the patients. Skin biopsies were obtained from the suspected lesions. The type of malignancy, the time of diagnosis of the malignancy, the presence of cutaneous metastasis, and the localization sites of the cutaneous malignancy were noted. Metastases of any kind were seen in 27.4% of cases. Cutaneous metastases were seen in 1.2% of cases and were most frequently localized on the anterior chest as nodules. Cutaneous metastasis was the first sign of internal malignancy in one case. It is concluded that cutaneous metastases occur rarely and the presentation of internal malignancy with skin involvement is uncommon.     

Malignant skin tumours in patients with inherited ichthyosis

Inherited ichthyoses are rare genodermatoses caused by mutations in the genes involved in epidermal development. Although there have been case reports on patients with ichthyosis who developed skin malignancies, it is still unknown whether or not patients with ichthyosis have an increased risk of skin malignancies. Here, we review case series of skin malignancies in patients with ichthyosis and show biological findings which might lead to cancer susceptibility. A survey of the literature revealed 28 cases of inherited ichthyoses with skin malignancy, including 12 cases of keratitis-ichthyosis-deafness (KID) syndrome, seven of autosomal recessive congenital ichthyosis, three of Netherton syndrome and six of miscellaneous ichthyosis. Twenty-four of the 28 cases developed single or multiple squamous cell carcinomas (SCCs). The age at diagnosis of the first skin malignancy ranged from 15 to 54 years. As patients with these particular subtypes of ichthyosis seem to be prone to skin malignancies, including SCC, at an unusually young age, routine cancer surveillance of these patients is strongly recommended.     

Bullous pemphigoid in Liguria: A 2-year survey

BACKGROUND: The epidemiology of bullous pemphigoid (BP) is not clear because of the heterogeneity of the disease, and its possible association with internal malignancies has been under debate for many years. We report the findings of a 2-year study on incident BP cases in the Liguria region of Italy. SUBJECTS AND METHODS: Thirty-two patients with BP were collected over the 2-year period. Diagnosis was made based on clinical findings and confirmed by histology, direct immunofluorescence (DIF) and indirect immunofluorescence (IIF) with salt-split skin and monkey oesophagus, and immunoblotting (IB). All patients were thoroughly investigated for possible malignancies and all were followed up for 6 months to monitor the response to treatment. RESULTS: DIF showed linear deposits at the dermoepidermal junction in all but one patient. IIF gave positive findings for 15 sera tested with monkey oesophagus and 20 tested with salt-split skin. IB gave positive findings in 19 cases. There was a malignancy in six cases, but no clinical or immunological features that could be considered to predict this occurrence. CONCLUSIONS: The findings of this study are in accordance with most of the data found in the literature, including the fact that IgG serum levels did not predict the course of the disease. Contrary to previous indications, IgE levels were not indicative of disease course either. Mucosal lesions, erythema multiform-like lesions, negative IIF findings and antibodies to AgPB2 were not a prediction for the development of malignancy.     

Leser-Trélat sign associated with Sézary syndrome

The Leser-Trélat sign is a rare but well known cutaneous indicator of internal malignancy, most commonly adenocarcinoma of the stomach. There have been only a few cases associated with lymphoproliferative malignancies. Sézary syndrome is a chronic leukemia/lymphoma characterized by generalized erythroderma and circulating Sézary cells. We describe a rare case of the Leser-Trélat sign associated with the Sézary syndrome. The skin sign was alleviated through combination chemotherapy.     

Tripe palms: a significant cutaneous sign of internal malignancy.

Tripe palms is a paraneoplastic keratotic skin sign of great predictive value. It is characterized clinically by a curious rugose thickening of the palms with an accentuation of the normal dermatoglyphic ridges and sulci. Histological examination reveals an undulant epidermis with hyperkeratosis, acanthosis and papillomatosis. More than 80 cases have been reported in the literature; 90% of them were associated with an internal malignancy, mostly a carcinoma of the lung or stomach. We herein report a 66-year-old Chinese man with adenocarcinoma of the lung who presented typical tripe palms. Recognition of this distinctive pattern should prompt a meticulous search for an underlying malignancy, particularly lung or gastric carcinoma.     

Cutaneous manifestations of internal malignancy

Background:

Many malignancies affecting the internal organs display cutaneous manifestations which may be either specific (tumor metastases) or nonspecific lesions.

Aims:

The study is aimed at determining the frequency and significance of cutaneous manifestations among patients with internal malignancy.

Materials and Methods:

750 cases of proven internal malignancy, who attended a cancer chemotherapy center in South India, were studied. Specific infiltrates were confirmed by histopathology, fine needle aspiration cytology (FNAC) and marker studies.

Results:

Out of the 750 patients with internal malignancy, skin changes were seen in a total of 52 (6.93%) patients.

Conclusion:

Cutaneous metastases (specific lesions) were seen in 20 patients (2.66%): contiguous in 6 (0.8%), and non-contiguous in 14 (1.86%). Nonspecific skin changes were seen in 32 patients (4.26%). None of our patients presented with more than one type of skin lesions. Herpes zoster was the most common nonspecific lesion noticed in our patients, followed by generalized pruritus, multiple eruptive seborrheic keratoses, bullous disorder, erythroderma, flushing, purpura, pyoderma gangrenosum, insect bite allergy and lichenoid dermatitis.     

Leukemia cutis in association With Grover's disease

Grover's disease (GD), or transient acantholytic dermatosis, is a persistent recurrent dermatosis that usually occurs in men older than 50 years. Rare cases of GD and hematologic malignancy in the same cutaneous biopsy specimen have been reported. We report a case of GD in association with leukemia cutis. A 72-year-old man with a history of myelodysplastic syndrome presented with numerous pruritic papules on the torso, which were clinically diagnosed as GD. A skin biopsy revealed foci of suprabasal acantholysis and dyskeratosis consistent with GD and dense aggregates of mononuclear atypical cells in the superficial dermis consistent with leukemia cutis. Direct immunofluorescence was negative. This case illustrates the need to consider a diagnostic skin biopsy in any patient who presents with classic clinical findings of GD if there is any indication that the patient may be at higher risk for a hematologic malignancy.     

Skin tumors of xeroderma pigmentosum (I)

Sixty-eight xeroderma pigmentosum (XP) patients, including 41 of Group A and 27 of XP-variant, were examined for skin malignancies such as squamous cell carcinoma (SCC), basal cell epithelioma (BCE), and malignant melanoma (MM). Approximately half of the patients developed skin malignancies on sunlight-exposed areas. The most frequent skin malignancy in both groups was BCE. In this survey, two cases with MM were found for the first time in Japan, one in Group A and one in XP-variant. The most important difference between Group A and XP-variant was in the age of onset of skin malignancies. The average age at the first excision of skin malignancies was 9 in Group A, while that of XP-variant was 32. In Group A, the youngest case was 3 years old, and most of the cases with skin malignancies were younger than 15. In XP-variant, on the contrary, the youngest case was 15 and most cases were older than 20. XP-variant patients were apt to have multiple lesions of BCE. The ratio of BCE to SCC was about 3:1 in Group A, and 8:1 in XP-variant. The strong tendency toward malignancy was seen only on the skin in both groups.     

Extramammary Paget's disease: prognosis and relationship to internal malignancy

Extramammary Paget's disease is a rare cutaneous adenocarcinoma, usually of epidermal origin and glandular differentiation and frequently associated with an underlying adnexal carcinoma and perhaps with underlying internal malignancy. One hundred ninety-seven cases of extramammary Paget's disease (196 cases reported in the English literature from 1962 to 1982 and one case of my own) are reviewed. It remains a rare cutaneous malignancy that occurs primarily in elderly people. It is seen more frequently in women than in men and occurs predominantly in vulvar and perianal locations. Twenty-six percent of patients with this disease will ultimately die of it or an associated internal malignancy. Twenty-four percent of patients with the disease have an associated underlying cutaneous adnexal adenocarcinoma. These patients have a higher mortality rate--46%--than patients with extramammary Paget's disease without underlying cutaneous adnexal adenocarcinoma. Twelve percent of patients with extramammary Paget's disease have an associated concurrent underlying internal malignancy. The location of the underlying internal malignancy appears to be closely related to the location of the extramammary Paget's disease--i.e., a perianal location is associated with adenocarcinoma of the digestive system, a penile-scrotal-groin location with genitourinary malignancy, etc. A directed internal malignancy search may be of benefit in patients who are diagnosed as having extramammary Paget's disease.     

Immunohistochemical localization of cathepsin L and cystatin A in normal skin and skin tumors

Cathepsin L, a cysteine proteinase, and cystatin A, an inhibitor of cysteine proteinases, are thought to regulate the invasion and metastasis of malignant cells. In this study, the expression of cathepsin L and cystatin A in skin tumors was investigated immunohistochemically in order to examine the relationship between these two enzymes in the pathophysiology of malignant cells. Formalin-fixed and paraffin embedded specimens from normal skin, seborrheic keratoses, and squamous cell carcinomas were reacted with polyclonal antibodies against rat cathepsin L or cystatin a which cross-react to human cathepsin L and cystatin A, respectively. The consequent immunostaining of these enzymes was observed to be strong in normal skin (4 cases) and seborrheic keratosis (6 cases). In well-differentiated squamous cell carcinoma (SCC) (9 cases), staining for cathepsin L and cystatin A was moderately positive in differentiated tumor cells and negative in undifferentiated SCC (5 cases). The degree of staining of these enzymes was inversely correlated with the differentiation of the malignant cells. These results suggest that the immunohistochemical analysis of cathepsin L and cystatin A is a useful indicator for an aspect of malignancy in human epidermal keratinocytes.     

A Case of Metastatic Renal Cell Carcinoma Mimicking Granuloma Pyogenicum

Renal cell carcinoma (RCC) is well known for its frequent metastasis and particularly to the lungs, liver, bones and brain, but metastasis to the skin is rare. We report here on a case of metastatic RCC in a 73-year-old man who presented with a 1.5 cm sized, moist, beefy-red and exophytic nodule on the scalp. The lesion had grown rapidly for 2 months and it clinically mimicked granuloma pyogenicum. A skin biopsy revealed a solid mass composed of clear cells with clear cytoplasm and oval hyperchromatic nuclei, and they were arranged in an alveolar pattern. As skin metastasis from renal cell carcinoma signals widespread systemic metastasis and a poor prognosis, clinicians should conduct a careful inspection of the skin of a patient with RCC and they should also have a high index of suspicion for finding a primary internal organ malignancy in the RCC patients who present with a skin lesion.     

Cutaneous scrotal metastasis: origins and clinical characteristics of visceral malignancies that metastasize to the scrotum

Cutaneous metastases occur in about 10% of patients with cancer, occasionally presenting as the initial sign of internal malignancy. Most often cutaneous metastases are an indicator of advanced cancer and are associated with a poor prognosis. The scrotum is a rare site of cutaneous metastasis, and metastatic tumor to the scrotum can be mistaken for other skin lesions. We reviewed the published literature regarding patients who developed cutaneous metastasis to the scrotum. We summarized the clinical characteristics of these men, including primary tumor sites, age at diagnosis, treatment regimens, interval between diagnosis of primary tumor and subsequent metastasis, and outcomes. We extensively searched the PubMed medical database for papers on visceral malignancies with metastasis to the scrotum. We limited our definition to solid organ tumors; thus lymphomas, sarcomas, and melanomas of the scrotum were excluded. We identified 29 patients who developed scrotal metastases from visceral cancers. The colon/rectum (34%), prostate (28%), and lung (14%) were the most frequent sites of tumor origin. The prognosis for these patients is poor: mean patient survival was only four months after diagnosis of metastatic skin lesions. Cutaneous metastasis to the scrotum is a rare manifestation of internal malignancies that most often represents an advanced and/or progressive cancer associated with a poor prognosis. Treatment is often unsuccessful, and the mean patient survival following scrotal metastasis is <4 months.     

Pemphigus vulgaris induced by radiotherapy

A 54-year-old male patient who had been suffering from lymphoma for four years developed pemphigus vulgaris three weeks after exposure to radiotherapy. Skin lesions were initially strictly confined to the irradiated area and later extended over other skin areas. The eruption rapidly improved with glucocorticosteroid therapy which could be stopped after six months. Thirteen cases of pemphigus following X-ray irradiation have been published, twelve of them being associated with an internal malignancy. Clinical data strongly indicate radiation therapy as a provoking factor for the development of pemphigus, but a possible role of the neoplasia in our patient cannot be ruled out. It is suggested that immunological disturbances associated with lymphoma lead to an autoimmune response after exposure to X-rays. Ionizing radiation may alter the antigenicity of the epidermal cell surface or unmask epidermal antigens.     

Seborrheic keratoses and cancer

BACKGROUND: The eruptive appearance of numerous seborrheic keratoses, the sign of Leser-Trélat, has been regarded as a reliable cutaneous marker of internal malignancy. OBJECTIVE: We have evaluated the possible association of malignant disease and the sign in 1752 consecutive cases of seborrheic keratoses. METHODS: First, the Swedish Cancer Registry was searched for records of malignancies in the study population (1958 to 1984), and the expected number of malignancies was calculated. Second, records of persons with malignancy within 1 year before or after the diagnosis of seborrheic keratosis were checked for the sign of Leser-Trélat. Third, a case control study was performed to evaluate the possibility of eruptive seborrheic keratoses among the noncancer patients in the study population. RESULTS: The results showed a slight increased risk of cancer in the study population (relative risk = 1.2; 95% confidence interval = 1.0 to 1.3), mainly because of an increased risk of cutaneous squamous cell carcinoma. In 62 patients with seborrheic keratoses, a malignancy (excluding skin) was diagnosed within 1 year before or after the diagnosis of seborrheic keratosis. Of these 62 patients, 6 were regarded as possibly having presented with the sign of Leser-Trélat. For every one of the 62 cases with seborrheic keratosis and malignancy within one year, an age- and sex-matched control patient without cancer was selected from the study population and the records were checked for sudden and eruptive seborrheic keratoses. Among the control patients, five were regarded as possibly having presented with the sign of Leser-Trélat. CONCLUSION: This study gives no evidence to support the opinion that eruptive seborrheic keratoses are related to internal cancer risk.     

Cutaneous leukocytoclastic vasculitis in dermatomyositis suggests malignancy

BACKGROUND: Dermatomyositis (DM) is a rare connective tissue disease which has been shown to be associated with an underlying malignancy. OBJECTIVE: Evaluation of the prevalence of malignancy in DM at our clinic and search for characteristics of the paraneoplastic form of disease. METHODS: Retrospective review of patient files and histology reports over the period from 1991 to 1998. RESULTS: 23 patients (14 women and 9 men) with DM could be identified in this time period with a median age at diagnosis of 48 years. Malignancies were found in 5 (22%) cases. The skin biopsies of all patients showed features of DM; in 7 cases, a leukocytoclastic vasculitis was detected. Four of the 5 cases with an associated malignancy demonstrated histologically a vasculitis in lesional skin, compared to only 3 out of 18 cases without malignancy (p < 0.05, Fisher's exact test). CONCLUSION: Our data suggest that vasculitis in lesional skin biopsies has a predictive value for the presence of underlying malignancy.     

Multiple Sclerotic Fibromas in an HIV‐Positive Patient Without Evidence of Cowden''s Disease

Dermatomyositis is an inflammatory condition of the skin and muscles, and an underlying malignancy is noted in 10% or more of cases. Clinical features of dermatomyositis include increasing general fatigue and proximal (thighs and shoulders) muscle weakness accompanied by erythematous lesions of the skin. There have been several distinct types of dermatomyositis described. Here we describe a case of vesiculo‐bullous dermatomyositis, which is a rare variant of dermatomyositis. A 49‐year‐old woman was admitted to our hospital with a painful erythematous vesicular eruption of the face, trunk and extremities. In addition, edema of the face and fever were observed. Clinically, dermatomyositis was considered because of typical skin rashes (Gottron's papules, periorbital heliotrope rash and poikiloderma) and serum creatine phosphokinase level of 1,031 IU/L. A skin biopsy was performed. Microscopically, subepidermal vesiculation with marked edema was present. Lymphoplasmacytic infiltration was also observed in the upper dermis. So far only a few case reports of vesiculo‐bullous dermatomyositis have been reported in the literature. It should be kept in mind that dermatomyositis may present subepidermal vesiculation in order to avoid a misdiagnosis and unnecessary delayed treatment. Furthermore, an internal malignancy should be considered in such a variant of dermatomyositis.