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Tumor-induced osteomalacia (TIO) is an acquired fibroblast growth factor 23 (FGF23)-related hypophosphatemic osteomalacia caused by phosphaturic mesenchymal tumors (PMTs) developed in the bone or soft tissue. Diagnostic delay should be addressed, and ideal techniques to localize PMTs and efficient treatment options should be explored to improve the outcomes of this rare disease. To clarify the detailed clinical course and outcomes of TIO patients, retrospective questionnaire surveys were conducted among physicians from the Japanese Society for Bone and Mineral Research (JSBMR) and the Japan Endocrine Society (JES). The primary survey collected the number of TIO patients between January 2007 and December 2018. The secondary survey aimed to obtain the detailed characteristics, laboratory data, and outcomes. Eighty-eight patients (52 males, mean: 52 years old) were included, and 24 patients were clinically diagnosed with TIO without localized PMTs. The median duration from the onset to detection of high FGF23 levels was 3.4 years, with 77 patients being initially misdiagnosed. Among the methods used to detect small, localized PMTs (≤10 mm), fluorine-18-fluorodeoxyglucose-positron emission tomography/computed tomography and somatostatin receptor scintigraphy were less sensitive than somatostatin receptor positron emission tomography/computed tomography (SRPET/CT). Systemic venous sampling (SVS) of FGF23 was performed in 53 patients; among them, SVS was considered useful for detecting localized PMTs in 45 patients with diverse tumor sizes. Finally, 45 patients achieved biochemical remission by surgery, 39 patients continued pharmaceutical treatment, including burosumab (11 patients), and four patients died. These results encouraged us to further increase the awareness of TIO and to improve the accessibility of SRPET/CT and SVS. Further evidence about the efficacy of new pharmaceutical treatments is awaited. © 2022 American Society for Bone and Mineral Research (ASBMR).

Tumor-induced osteomalacia TIO is a rare paraneoplastic syndrome caused by excessive production of fibroblast growth factor 23 FGF23 by a tumor. Previous studies have revealed generalized mineralization defects and low areal bone mineral density aBMD in TIO. However, data on the bone microarchitecture in TIO are limited. In this study, we evaluated the microarchitecture in the peripheral distal radius and tibia and axial lumbar spine skeleton using high-resolution peripheral quantitative computed tomography HR-pQCT and trabecular bone score TBS and investigated related factors in a large cohort of Chinese patients with TIO. A total of 186 patients with TIO who had undergone dual-energy X-ray absorptiometry DXA or HR-pQCT scans were enrolled. Compared with age-, sex- and BMI-matched healthy controls, TIO patients n=113 had lower vBMD, damaged microstructure and reduced bone strength in the peripheral skeleton, especially at the tibia. The average TBS obtained from 173 patients was 1.15 ± 0.16. The proportion of patients with abnormal TBS

Background Castleman disease (CD) is a lymphoproliferative B-cell disease that is diagnosed from lymphoid hyperplasia with vascular proliferation. Symptoms may include fever, night sweats, and weight loss. Cutaneous manifestations often may go unnoticed since little has been described in the literature regarding them. Materials and methods A search of CD with cutaneous manifestations was performed in PUBMED, ProQuest, Ovid, Scopus, EMBASE, and Medline. All articles included patients over 18 years of age with a diagnosis of CD and cutaneous manifestations. Results A total of 68 articles were included. The most common cutaneous manifestations include paraneoplastic pemphigus and erythematous-brown plaques, papules, or nodules. Patients presenting with these manifestations should always have a thorough physical exam, and clinicians should try to identify any palpable lymph nodes. A complete workup to rule out other neoplasias needs to be performed as well. Conclusions A better understanding of these skin manifestations of CD may help physicians promptly diagnose and reconsider the path of diagnostic tests to identify this entity.

To describe our clinical experience with surgical treatments for sinonasal phosphaturic mesenchymal tumors diagnosed at our institution.Retrospective case series.Affiliated Sixth People's Hospital, Shanghai Jiao Tong University.We retrospectively reviewed the medical records of 10 patients diagnosed with phosphaturic mesenchymal tumors associated with tumor-induced osteomalacia between December 2014 and October 2019.There were 4 men and 6 women with a disease course of 1 to 19 years. All patients exhibited hypophosphatemia and tumor-induced osteomalacia. The tumor was located in the sinonasal region, frontal bone, and temporal bone in 8 patients, 1 patient, and 1 patient, respectively. Technetium-99m octreotide scintigraphy was used for tumor localization in 4 cases. Six patients underwent endoscopic resection; the remaining 4 underwent unilateral transorbital anterior and posterior ethmoid artery ligation + endoscopic resection, endoscopic resection + skull base repair, internal carotid artery stenting + transcatheter arterial embolization + temporal bone tumor excision + adipose tissue plugging, and endoscopic resection + transfrontal craniotomy (n = 1 each). Two patients had a history of incomplete endoscopic resection. All patients achieved clinical remission and normalized biochemical indices after surgery. Only 1 patient developed recurrence and died of a brain hernia.A diagnosis of sinonasal phosphaturic mesenchymal tumors should be based on a combination of clinical, imaging, and pathological findings. Technetium-99m octreotide scintigraphy helps in locating the tumor. Complete surgical excision guarantees clinical remission, and preoperative transcatheter arterial embolization or feeding artery ligation may reduce intraoperative bleeding in cases of highly vascularized tumors.

A 60‐year‐old woman was urgently admitted to our hospital because of vertigo and left hemiplegia. Laboratory examination showed thrombocytopenia, high levels of D‐dimer and carcinoembryonic antigen. Brain magnetic resonance imaging (MRI) revealed multiple bilateral cerebral infarctions. Chest computed tomography (CT) showed an irregularly shaped tumor in the upper lobe of the left lung and mediastinal node swelling. The histopathological findings revealed adenocarcinoma negative for anaplastic lymphoma kinase fusion gene, sensitive epidermal growth factor receptor mutations. A diagnosis of lung adenocarcinoma initially presenting as arterial thromboembolism was made, and she was treated with direct oral anticoagulant (DOAC). Subsequently, pembrolizumab therapy was initiated because tumor cells were positive for programmed cell death protein 1 (PD‐L1;60%), and resulted in reduction of the tumor with normalization of the platelet count and d‐dimer. The treatment has been continued for over one year without any recurrence of the disease or thromboembolism., The prognosis in patients with NSCLC initially presenting as Trousseau's syndrome is extremely poor. This is the first report in which a patient was successfully treated with DOAC and immune‐check point inhibitor in lung adenocarcinoma initially presenting as Trousseau's syndrome.

Accumulating data on patients with autoimmune encephalitis have shed light on specificities concerning clinical presentation and outcomes, which are dependent on the antigen targeted by the autoantibodies found in the patients' cerebrospinal fluid or sera. Such specificities include seizure-related clinical manifestations as well as the responsiveness to antiepileptic drugs. Although increased enthusiasm accompanies the discovery of novel antibodies and their associated clinical syndromes, several issues remain unsettled. First, it appears that therapy needs to be personalized in the view of the severity of each antibody-mediated syndrome, patient-related characteristics, and timing of treatment. Second, the lack of randomized controlled trials is a major drawback in the formulation of an appropriate immunotherapeutic strategy. In this review, we discuss the novel developments and challenges for the diagnosis and treatment of epilepsy in patients with well-characterized autoimmune encephalitis, and delineate the principles for a rational approach toward precision medicine in this emerging field.

Eosinophilic dermatosis of hematological malignancy is a paraneoplastic skin eruption associated with chronic lymphocytic leukemia and other B-cell malignancies. It clinically resembles an insect bite reaction and it can precede the symptoms of the hematological malignancy or be related to a more aggressive course. Different treatments have been proposed, but partial response and recurrence are frequent. Herein, we describe a case of eosinophilic dermatosis associated with mantle cell lymphoma with remission after lenalidomide therapy.

Doege‐Potter syndrome is a rare hypoglycemic paraneoplastic disorder. This case describes that severe and symptomatic hypoglycemia can occasionally be due to a rare malignant neoplasm, and the differential diagnosis of malignancy should not be overlooked in this setting.

OBJECTIVES To describe the natural history and factors influencing diagnostic delays among patients with autoimmune blistering diseases of the mouth. MATERIALS AND METHODS In this cross-sectional study, 27 newly diagnosed patients were interviewed, and professional and patient delays were calculated. Disease extent and severity scores were determined using Saraswat scoring system. RESULTS Twenty-seven patients were interviewed and examined. Patient delay was significantly longer in patients who had desquamative gingivitis as initial presentation, in those who tried to use home remedies and over the counter medications, and in patients with less severe disease. Most patients (n = 21 [77.7%]) made more than one consultation, and the mean time needed to reach a definitive diagnosis (i.e. professional delay) was 83.2 ± 21.4 days (range from 21 to 130 days). Professional delay was significantly correlated with the number of previous consultations (r = .78) and was significantly longer in patients who had desquamative gingivitis as initial presentation. CONCLUSION Diagnosis of oral blistering diseases is often delayed. Diagnostic delay is more common in patients presenting with desquamative gingivitis and those with less severe disease. Improving patients and healthcare professionals' awareness about oral blistering diseases might help reduce diagnostic delay.

Objectives: An association between cancer and dermatomyositis (DM) is well recognized. The high frequency of malignancies detected close to DM diagnosis suggests that DM can be a paraneoplastic syndrome. Recently anti-TIF1-gamma has been discovered to be associated with cancer and DM. A meta-analysis claimed pooled sensitivity of anti-p155 for diagnosing cancer-associated DM to be 78% and specificity to be 89%. Thus anti-TIF1-gamma has shown promising results as a marker forcancer-associated DM . However, none of the studies evaluated anti-TIF1-gamma association with cancer with or without other rheumatic disorders than DM. To clarify the specificity of anti-TIF1-gamma antibodies as a biomarker for cancer-associated DM we analyzed frequency of anti-TIF1-gamma antibodies in other cancer associated rheumatic syndromes as well as in cancer patients and healthy controls. Methods: Sera from patients with paraneoplastic rheumatic syndrome (n=91), patients with solid cancer (n=95) and healthy controls (n=80) were analyzed for the frequency of anti-TIF1-gamma IgG by ELISA using a commercially available recombinant TIF1-gamma protein as coating antigen. The cut-off value was calculated by adding 2SD to the mean OD value of 80 healthy controls. Results: Positivity for anti-TIF1-gamma IgG was 3,3% (n=3) in patients with paraneoplastic rheumatic syndrome, 3,1% (n=3) in cancer patients and 1,3% (n=1) in healthy controls. There was no significant difference in positivity between the groups (p>0,05). Conclusion: AntiTIF1-gamma antibodies are rarely present in patients with solid cancers or paraneoplastic rheumatic syndromes. This finding strengthens the approach to use anti-TIF1-gamma IgG as marker for cancer-associated DM. This article is protected by copyright. All rights reserved.

Tumor‐induced osteomalacia (TIO) is caused by phosphaturic mesenchymal tumors producing fibroblast growth factor 23 (FGF23) and is characterized by impaired phosphate metabolism, skeletal health, and quality of life. UX023T‐CL201 is an ongoing, open‐label, phase 2 study investigating the safety and efficacy of burosumab, a fully human monoclonal antibody that inhibits FGF23, in adults with TIO or cutaneous skeletal hypophosphatemia syndrome (CSHS). Key endpoints were changes in serum phosphorus and osteomalacia assessed by transiliac bone biopsies at week 48. This report focuses on 14 patients with TIO, excluding two diagnosed with X‐linked hypophosphatemia post‐enrollment and one with CSHS. Serum phosphorus increased from baseline (0.52 mmol/L) and was maintained after dose titration from week 22 (0.91 mmol/L) to week 144 (0.82 mmol/L, p

Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare paraneoplastic intraocular disease that causes progressive visual loss in patients driven by an IgG factor associated with an underlying malignancy. Characteristic ocular findings include exudative retinal detachment, rapid cataract formation and uveal melanocytic tumours. The awareness and documentation of BDUMP has increased during the past decade, and the increasing amount of data collected demonstrates the effect of treatment with plasmapheresis and the value of diagnostic tools in BDUMP such as genetic and immunologic investigations. The literature of BDUMP has not been reviewed since 2003, and there is a growing need for an updated review on diagnosis and management of BDUMP. We review the literature and report a case of BDUMP with a white ciliary body tumour, iris rubeosis, increased iris pigmentation and cataract.

Paraneoplastic pemphigus (PNP) is a rare but severe multiorgan autoimmune disease that occurs in the presence of an underlying neoplasm. It is clinically characterized by a painful oral stomatitis, and a range of skin eruptions. In PNP, autoantibodies are directed against the intracellular desmosomal and hemidesmosomal plaque proteins of the plakin family: envoplakin, periplakin, desmoplakin, BP230 and plectin. In addition, the desmosomal proteins desmoglein (Dsg) 3 and less frequently Dsg 1 are targeted, as well as the protease inhibitor alpha-2-macroglobulin-like antigen-1 (A2ML1).(1-4) Diagnosing PNP largely depends on the demonstration of these autoantibodies. Immunoblotting and immunoprecipitation are sensitive and specific methods to detect these circulating antibodies. This article is protected by copyright. All rights reserved.

Elastosis perforans serpiginosa (EPS) is a rare skin disorder in which there is transepithelial elimination of elastin fibers. It belongs to a group of perforating disorders of which there are four classic types. The EPS type is extremely rare. There have been no previous reports of elastosis perforans serpiginosa occurring as a paraneoplastic phenomenon. We report a case of paraneoplastic elastosis perforans serpiginosa in the setting of stage 4 ovarian cancer.

A 63-year-old Japanese man with non-Hodgkin B-cell lymphoma presented with erythematous skin lesions on his entire body, with oral, ocular and anal mucosal lesions. The patient was diagnosed with paraneoplastic pemphigus. Immunofluorescence showed both immunoglobulin (Ig)G and IgA antibodies to keratinocyte cell surfaces. Various immunoblot and enzyme-linked immunosorbent assays showed both IgG and IgA antibodies to various autoantigens, including desmogleins, desmocollins, envoplakin, periplakin and bullous pemphigoid antigens. This was a unique case with a very rare autoantibody profile in paraneoplastic pemphigus.

Introduction Myelodysplastic syndrome (MDS) comprises a heterogeneous group of clonal disorders of haematopoietic stem cells, characterised by dysplastic haematopoiesis and dysregulated apoptosis resulting in various degrees of cytopenia, whereas canonical cytologic, cytogenetic and histopathologic findings guiding the diagnosis MDS are widely accepted, the MDS-phenotype can be masked by coexisting/paraneoplastic immunologic disease. Autoimmune disorders have an estimated incidence of 10% among patients suffering from MDS and are causally related to increased morbidity and mortality, younger age at diagnosis and more complex genetics. Conversely, systemic inflammatory disorders may be an early manifestation of MDS, show good response to immunosuppressive therapy and frequently disappear during the course of specific haematologic therapy. Objective Monocentric report on clinical phenotypes found in MDS or bone marrow failure with paraneoplastic inflammatory disease. Methods Clinical case reports and systematic review about MDS pathophysiology and treatment. Results We report eight patients diagnosed with MDS or bone marrow failure, who presented with paraneoplastic autoimmune diseases. Six of eight patients were treated with the hypomethylating agent 5-azacytidine, three of which achieved meaningful response with regard to inflammation control and haematologic recovery. Conclusions As paraneoplastic syndromes are often mistakenly diagnosed as idiopathic autoimmune disorders, we propose that coexistence of an underlying myelodysplastic syndrome should be considered early in the diagnostic work up. 5-Azacytidine is effective in controlling paraneoplastic inflammation.

Paraneoplastic pemphigus (PNP) is a rare, life-threatening, autoimmune, mucocutaneous blistering disease associated with neoplasia. Both humoral and cellular immunity are involved in the pathogenesis of PNP. Characteristically, PNP has a diverse spectrum of clinical and immunopathological features. We retrospectively analyzed 12 Korean patients with PNP who were diagnosed between 1993 and 2011. We performed analysis of the clinical features, clinical outcomes, underlying neoplasia, histological features and laboratory findings. All of the patients except one had severe mucosal involvement. Two patients had only mucosal lesions but no cutaneous involvement was observed. Erythema multiforme or lichen planus-like eruptions rather than bullous lesions were more commonly observed skin rashes. The most common histological features were interface dermatitis and apoptotic keratinocytes. There were associated hematological-related neoplasms in 11 patients, with Castleman's disease (n = 4) as the most frequent. Twelve patients were followed for 5-148 months (mean, 43.0). The prognosis depended on the nature of the underlying neoplasm. Six patients died due to respiratory failure (n = 3), postoperative septicemia (n = 1), lymphoma (n = 1) and sarcomatosis (n = 1). The 2-year survival rate was 50.0%, and the median survival period after diagnosis was 21.0 months. Immunoblotting was performed in 12 patients and autoantibodies to plakins were detected in 11 patients. The results of this study demonstrated the clinical, histological and immunological diversity of PNP. Widely accepted diagnostic criteria that account for the diversity of PNP are needed.

Tumor-induced osteomalacia (TIO) is an acquired form of hypophosphatemia. Tumor resection leads to cure. We investigated the clinical characteristics of TIO, diagnostic methods, and course after tumor resection in Beijing, China, and compared them with 269 previous published reports of TIO. A total of 94 patients with adult-onset hypophosphatemic osteomalacia were seen over a 6-year period (January, 2004 to May, 2010) in Peking Union Medical College Hospital. After physical examination (PE), all patients underwent technetium-99m octreotide scintigraphy (99Tcm-OCT). Tumors were removed after localization. The results demonstrated that 46 of 94 hypophosphatemic osteomalacia patients had high uptake in 99Tcm-OCT imaging. Forty of them underwent tumor resection with the TIO diagnosis established in 37 patients. In 2 patients, the tumor was discovered on PE but not by 99Tcm-OCT. The gender distribution was equal (M/F = 19/20). Average age was 42 ± 14 years. In 35 patients (90%), the serum phosphorus concentration returned to normal in 5.5 ± 3.0 days after tumor resection. Most of the tumors (85%) were classified as phosphaturic mesenchymal tumor (PMT) or mixed connective tissue variant (PMTMCT). Recurrence of disease was suggested in 3 patients (9%). When combined with the 269 cases reported in the literature, the mean age and sex distribution were similar. The tumors were of bone (40%) and soft tissue (55%) origins, with 42% of the tumors being found in the lower extremities. In summary, TIO is an important cause of adult-onset hypophosphatemia in China. 99Tcm-OCT imaging successfully localized the tumor in the overwhelming majority of patients. Successful removal of tumors leads to cure in most cases, but recurrence should be sought by long-term follow-up. © 2012 American Society for Bone and Mineral Research.

OBJECTIVE. IgG4-related disease (IgG4-RD) is a fibroinflammatory disease of unclear etiology. Some studies suggest that IgG4-RD predisposes patients to malignancy or is a forme fruste of cancer, but we have frequently observed IgG4-RD patients who have a history of malignancy preceding the clinical onset of IgG4-RD. This study was undertaken to characterize IgG4-RD in the setting of previous malignancy diagnosis. METHODS. We identified IgG4-RD patients with a history of invasive malignancy from a well-defined cohort of 125 patients and compared their malignancy history to those of 2 reference groups. First, we calculated a standardized prevalence ratio against general US population estimates from the Surveillance, Epidemiology, and End Results (SEER) database. Second, we identified up to 5 age- and sex-matched controls for each case and calculated the odds of malignancy among those with IgG4-RD compared to controls, using conditional logistic regression. RESULTS. The mean ± SD age at IgG4-RD onset was 50.3 ± 14.9 years, and 61% of the patients were male. Twenty (16%) had been diagnosed as having malignancies (total 21 malignancies) before the diagnosis of IgG4-RD. The observed prevalence of malignancy in this cohort was 2.5 times higher (95% confidence interval [95% CI] 1.1–3.6) than expected compared to the SEER database. Compared to matched controls, the frequency of history of malignancy was >3-fold higher in IgG4-RD patients (95% CI 1.6–6.2). CONCLUSION. Our findings suggest that, in a subset of patients with IgG4-RD, malignancy may be associated with subsequent IgG4-RD development. Potential explanations include shared risk factors for both IgG4-RD and cancer, the triggering by cancer of autoantigen expression leading to IgG4-RD, and an increased risk of IgG4-RD resulting from cancer treatment.

Paraneoplastic pemphigus (PNP) is an autoimmune bullous disease, which associates mainly with lymphoproliferative neoplasms. Bronchiolitis obliterans (BO) with progressive respiratory failure is a significant cause of death in PNP. We report a case of PNP associated with follicular lymphoma and BO, which showed findings suggesting coexistence of bullous pemphigoid (BP). The patient showed bullous and ulcerative lesions on the lips and oral cavity, and flaccid blisters on the trunk and thighs associated with anti-desmoglein (Dsg)3 antibodies. At later disease stage after commencement of treatment, anti-BP180 antibodies and tense blister formation were observed. It was proposed that persistent interface dermatitis is the first event in PNP, and subsequently induce the production of autoantibodies to Dsg and components of the basement membrane zone, resulting in both intraepidermal and subepidermal blisters. We speculate that interface dermatitis caused by autoreactive T cells induced autoantibody production against Dsg3, and subsequently against BP180.

Hemophagocytic lymphohistiocytosis (HLH) is characterized by dysregulated immune activation. Primary HLH involves hereditary deficits in cytotoxic lymphocytes while secondary HLH is triggered by extrinsic factors. The HLH-2004 criteria are widely used for clinical diagnosis, yet their specificity for HLH or their ability to differentiate primary from secondary disease is unclear, potentially leading to inappropriate treatment. We describe several cases where fulfillment of HLH-2004 criteria obscured the diagnoses of underlying malignancies and delayed curative management. These issues are remedied without waiting for genetic testing results through an alternative diagnostic approach using flow cytometry-based immunologic assays and a thorough investigation for malignancy.

Ornithine transcarbamylase deficiency (OTCD) disrupts the metabolic pathway responsible for converting nitrogenous waste to urea, allowing for excretion. When impaired, ammonia levels accumulate in the blood resulting in severe, sometimes life-threatening toxicities. Abnormalities of the urea cycle are often inherited, though there are some rarer acquired forms. We describe two cases of acquired OTCD in pediatric patients with fibrolamellar hepatocellular carcinoma (FL-HCC). We detail its presentation and management, explore potential underlying pathophysiology, and propose a practice change to optimize care of FL-HCC patients.

Hypercalcemic nude mice bearing a canine adenocarcinoma (CAC-8) model of humoral hypercalcemia of malignancy (HHM) were treated daily with gallium nitrate (60 mg/kg of elemental gallium subcutaneously (SC) on day 0, followed by 20 mg/kg/day) for 5 days. Gallium nitrate significantly decreased (p < 0.01) serum calcium in tumor-bearing animals on days 2 and 5 of treatment (mean 13.7 ± 0.7 mg/dl on day 0 versus 11.6 ± 0.3 on day 2 and 12.4 ± 0.5 on day 5). Urinary calcium excretion was decreased (p < 0.05) in the gallium-treated, tumor-bearing animals (0.11 ± 0.01 mg calcium/mg creatinine) compared with hypercalcemic tumor-bearing mice (0.30 ± 0.06). Both nontumor control and tumor-bearing mice treated with gallium nitrate lost body weight during the treatment period (p < 0.01). Gallium nitrate had no effect on tumor growth. Histomorphometric evaluation of lumbar vertebrae stained for tartrate-resistant acid phosphatase revealed a significant decrease (p < 0.05) in the number of osteoclasts/mm trabecular bone and perimeter of trabecular bone lined by active osteoblasts (p < 0.01) in the gallium-treated tumor-bearing mice compared with tumor-bearing controls. Osteoclast length (mm) was significantly increased in both the nontumor and tumor-bearing gallium-treated animals (p < 0.05) compared with nontumor and tumor-bearing control mice. Serum tumor necrosis factor α (TNF-α) levels were increased in tumor-bearing animals, but gallium nitrate had no effect on circulating levels (not detectable in nontumor control mice versus 82 ± 21 pg/ml in tumor-bearing mice and 107 ± 12 pg/ml in gallium-treated tumor-bearing mice). Concentrations of gallium in bone were undetectable in untreated control mice (

Intravenous aminohydroxypropylidene bisphosphonate (APD) normalizes serum calcium in most hypercalcemic cancer patients, however the optimal therapeutic scheme has not been established. We compared in a randomized prospective trial the efficacy and the tolerance of APD given as a 3-day treatment of daily 2-h infusions of 0.5 mg/kg·d in 250 ml of saline (group A) with single 24-h infusions of 1.5 mg/kg (group B) or of 0.5 mg/kg in 1 liter of saline (group C). Thirty-three cancer patients remaining hypercalcemic after a 48-h rehydration period were included and monitored daily until normocalcemia or treatment failure was documented. Serum calcium became normal in all but 1 patient (in group C) but remained normal for only 1 or 2 days in 4 other patients (1 in A, 1 in B, 2 in C). The decline in total or ionized serum calcium was slightly less marked in group C than in the two other groups, but the differences were not significant. The fall of fasting urinary calcium excretion was however significantly less rapid in group C (p < 0.05 from day 1 to day 4). Serum concentrations of iPTH and 1,25-dihydroxyvitamin D [1,25-(OH)2D] increased significantly in the three groups. Serum magnesium concentrations fell slightly from 1.41 ± 0.05 to 1.28 ± 0.04 mEq/liter (p < 0.001) after rehydration but returned to normal after APD administration (day 5, 1.52 ± 0.04 mEq/liter, p < 0.001 versus day 0). On the other hand, APD induced a fall in serum phosphate levels, from 2.9 ± 0.1 to 2.3 ± 0.1 mg/dl on day 4 (p < 0.001), without any significant change in TmP/GFR. Treatment was very well tolerated; we only observed 3 cases of drug-induced fever, 1 in each group. Based on this and other dose-response trials, we recommend a total dosage of 1.0 to 1.5 mg of APD/kg body weight for the therapy of tumor-associated hypercalcemia; this treatment can be safely and efficiently given as a single 24 h infusion or as daily 2 h infusions for 3 days.

The skin often mirrors changes in the organism it envelops. Many neoplastic diseases that affect internal organs display cutaneous manifestations, which may be the presenting signs and symptoms of the underlying malignancy. These may reflect direct involvement of the skin by the tumor (ie, tumor metastasis) or indirect involvement, in which changes in the skin occur in the absence of malignant cells. This review focuses on the latter conditions, which are often referred to as paraneoplastic dermatoses. Included in the discussion are the cutaneous manifestations of inherited syndromes that are associated with an increased risk of internal malignancy, cutaneous changes in patients with hormone-secreting tumors, and the wide spectrum of proliferative and inflammatory dermatoses that have been associated with internal cancer.

Paraneoplastic pemphigus is the term used for an exclusive subset of pemphigus. The clinical lesions may resemble pemphigus, pemphigoid, erythema multiforme, graft-vs.-host disease, or lichen planus. A common denominator in all patients is the concomitant occurrence of either occult or confirmed systemic neoplasm. It is imperative to confirm the diagnosis through microscopy, where intraepidermal suprabasal cleavage, epidermal acantholysis, dyskeratotic keratinocytes and vacuolar changes in the basal epidermis, interfacial dermatitis, and epidermal exocytosis can be seen. Furthermore, the deposition of immunoglobulin G (IgG) and complement in the epidermal intercellular spaces, detected by direct and/or indirect immunofluorescence, is equally crucial for confirming the diagnosis.