DIPNECH: when to suggest this diagnosis on CT.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is an under-recognized disease characterized by proliferation of neuroendocrine cells in the bronchial wall. It is considered a pre-invasive lesion for lung carcinoid tumours and is found in 5.4% of patients undergoing surgical resection for lung carcinoid tumours. Other manifestations of DIPNECH include bronchial obstruction and formation of tumorlets. DIPNECH preferentially affects middle-aged women. Patients are either asymptomatic or present with long-standing dyspnoea due to obstructive syndrome that can be mistaken for asthma. At CT, mosaic attenuation with multiple small nodules is very suggestive of DIPNECH. The aim of this review is to describe DIPNECH-related CT features and correlate them with histology, in order to help radiologists suggest this diagnosis and distinguish DIPNECH from other causes of mosaic perfusion.

[Mastitis revealing Churg-Strauss syndrome]. / Mastite révélatrice d'un syndrome de Churg-Strauss.

BACKGROUND: Churg-Strauss syndrome often involves the skin, and this may sometimes reveal the disease. OBSERVATION: A 25-year-old woman was referred to a gynaecologist for inflammation of the right breast with breast discharge. Cytological analysis of the liquid showed numerous inflammatory cells, particularly polymorphonuclear eosinophils and neutrophils. Ultrasound examination of the breast was consistent with galactophoritis. CRP was normal, and hypereosinophilia was seen. The patient was subsequently referred to a dermatology unit. Skin examination revealed inflammation of the entire breast, which was painful, warm and erythematous; the border was oedematous with blisters. Necrotic lesions were also present on the thumbs and knees. Skin biopsy of the breast showed a dermal infiltrate with abundant infiltrate of polymorphonuclear eosinophils, including patchy necrosis and intraepidermal vesicles. Histological examination of a biopsy sample from a thumb revealed eosinophilic granuloma and leukocytoclastic vasculitis. The patient was also presenting asthma, pulmonary infiltrates and mononeuropathy at L3, consistent with Churg-Strauss syndrome. DISCUSSION: Breast involvement in Churg-Strauss syndrome is very rare (only one other case has been reported). This is the first case in which the breast condition revealed the disease. Cutaneous involvement of the breast is, however, also compatible with Wells' cellulitis. The lesions quickly disappeared with 1mg/kg/d oral prednisolone.

[Cutaneous mucormycosis caused by Rhizopus microsporus]. / Mucormycose cutanée à Rhizopus microsporus.

BACKGROUND: Mucormycosis are rare fungal infections occurring chiefly in the lung or the rhinocerebral compartment, particularly in patients with immunodeficiency or mellitus diabetes. We report the case of an elderly patient with cutaneous mucormycosis caused by Rhizopus microsporus. PATIENTS AND METHODS: An 89-year-old man presented a skin lesion of the forearm rapidly becoming inflammatory and necrotic. The patient had been treated for 2months with oral corticosteroids for idiopathic thrombocytopenia. Histological and mycological examination of the skin biopsy revealed the presence of a filamentous fungus, R. microsporus. The outcome was unfavorable, despite prescription of high-dose liposomal amphotericin B. DISCUSSION: Mucormycosis are infrequent opportunistic infections caused by angio-invasive fungi belonging to the Mucorales order. Cutaneous presentations are rare, and in rare cases the species R. microsporus is isolated in clinical samples. Diagnosis is based on histological examination highlighting the characteristic mycelium within infected tissue, together with ex vivo mycological identification using morphological and molecular methods. Treatment consists of liposomal amphotericin B combined with debridement surgery. CONCLUSION: R. microsporus is a marginal fungal species rarely isolated in clinical practice, and even less in dermatology departments. This clinical case report highlights the severity of infection with this fungus, particularly in the absence of early surgery.

Primary cutaneous Ewing sarcoma: a systematic review focused on treatment and outcome.

BACKGROUND: Despite intensive treatment, the overall prognosis of Ewing sarcoma of the bone remains poor. Primary cutaneous Ewing sarcoma very rarely occurs and the prognosis has been reported to be better in some small series. All cases of Ewing sarcoma are currently treated in the same way, regardless of their location. OBJECTIVES: To determine whether Ewing sarcoma of the bone and primary cutaneous Ewing sarcoma are different in terms of epidemiology and prognosis. METHODS: A systematic review of the literature was carried out using the keywords 'cutaneous Ewing's sarcoma', 'primary Ewing's sarcoma of skin' and 'primary neuroectodermal tumour and skin' in the Medline database. Series of five or more cases were included. RESULTS: Six series met the inclusion criteria, making a total of 61 patients. Median age at diagnosis was 17 years and 33% were male. The median size of the tumour was 2·3 cm. The treatment consisted of surgery in all cases, adjuvant multiagent chemotherapy in 69% of cases, adjuvant chemoradiotherapy in 38% of cases and adjuvant radiotherapy without adjuvant chemotherapy in 3% of cases. Six patients developed metastases, four of whom died. The overall survival was 93% and the 10-year probability of survival was estimated at 91% (95% confidence interval 83-100). CONCLUSION: This systematic review demonstrated epidemiological and prognostic differences between Ewing sarcoma of the bone and primary cutaneous Ewing sarcoma. Primary cutaneous Ewing sarcoma has a female predominance, occurs at a later age, but, more importantly, has a better outcome. Multimodal therapy for Ewing sarcoma is associated with immediate and long-term morbidity and mortality. Although the size of our study does not allow a definitive conclusion about treatment modalities, we suggest that a less toxic approach compared with conventional treatment should be investigated in primary cutaneous Ewing sarcoma.

Clinical and molecular practice of European thoracic pathology laboratories during the COVID-19 pandemic. The past and the near future.

BACKGROUND: This study evaluated the consequences in Europe of the COVID-19 outbreak on pathology laboratories orientated toward the diagnosis of thoracic diseases. MATERIALS AND METHODS: A survey was sent to 71 pathology laboratories from 21 European countries. The questionnaire requested information concerning the organization of biosafety, the clinical and molecular pathology, the biobanking, the workload, the associated research into COVID-19, and the organization of education and training during the COVID-19 crisis, from 15 March to 31 May 2020, compared with the same period in 2019. RESULTS: Questionnaires were returned from 53/71 (75%) laboratories from 18 European countries. The biosafety procedures were heterogeneous. The workload in clinical and molecular pathology decreased dramatically by 31% (range, 3%-55%) and 26% (range, 7%-62%), respectively. According to the professional category, between 28% and 41% of the staff members were not present in the laboratories but did teleworking. A total of 70% of the laboratories developed virtual meetings for the training of residents and junior pathologists. During the period of study, none of the staff members with confirmed COVID-19 became infected as a result of handling samples. CONCLUSIONS: The COVID-19 pandemic has had a strong impact on most of the European pathology laboratories included in this study. Urgent implementation of several changes to the organization of most of these laboratories, notably to better harmonize biosafety procedures, was noted at the onset of the pandemic and maintained in the event of a new wave of infection occurring in Europe.

[Efficacy and risks of topical 5-fluorouracil in Darier's disease]. / Traitement de la maladie de Darier par 5-fluorouracile topique: quelle efficacité, quels risques?

BACKGROUND: Darier's disease, an autosomal dominant disorder, is often resistant to therapy. There have been few encouraging reports in recent years of treatment using topical 5-fluorouracil (5FU) in this indication. We describe three cases of Darier's disease treated with Efudix: though it initially proved very effective, after several months this treatment became inefficacious. PATIENTS AND METHODS: Case 1: a 16-year-old girl with Darier's disease refractory to conventional treatments. Treatment with topical 5FU was initiated. After 3 weeks, her cutaneous lesions had practically disappeared, leaving only pigmented scars. At 6 months, worsening of the disease was controlled by increasing 5FU. At 11 months, the disease worsened and 5FU, which proved inefficient, was stopped. Case 2: a 59-year-old woman presenting treatment-resistant Darier's disease was given 5FU. After 1 week, improvement began and was evident at 4 months. However, after 13 months of treatment, the disease progressed, and increased 5FU proved completely ineffective. Case 3: a 29-year-old woman was hospitalized for inflammatory Darier's disease. Topical 5FU was applied to the left half of the body and a short course of oral corticosteroids was prescribed. After 10 days of treatment, there was a clear improvement. After 6 weeks, the patient showed episodes of healthy skin. However after 3 months, the patient stopped taking her treatment due to inefficacy. DISCUSSION: While topical 5FU seems to be effective initially in treating Darier's disease, this efficacy subsides over time. Although no adverse effects were noted in our patients, use of 5FU can result in serious adverse reactions. Because of the loss of efficacy of this treatment following initial success, coupled with its poorly evaluated safety, caution must be exercised when prescribing it, particularly in patients with dihydropyriminidine dehydrogenase (DPD) deficiency or for use on damaged skin.

[Slowly regressing acute pandysautonomia associated with esophageal achalasia: a case report]. / Pandysautonomie aigue lentement regressive associee a une achalasie de l'oesophage: a propos d'un cas.

Acute pandysautonomia is a rare acute autonomic neuropathy that mainly affects young women. We report a case of idiopathic acute pandysautonomia associated with an esophageal achalasia in a 30-year-old woman. The clinical features were inaugural dysphagia followed by signs of parasympathetic failure of the entire digestive tract, bladder and pupils. Twenty-four hours of electrocardiographic recording showed involvement of sympathetic adrenergic nerves. Esophageal achalasia was patent on esophageal manometry. Upper digestive tract motility was first involved and then extended to the entire digestive tract with intestinal obstruction, which required emergency ileostomy. Recovery of autonomic functions was slow. After 16 months, dysphagia and gut paresis improved and digestive continuity was restored. In case of subacute intestinal pseudo-obstruction associated with autonomic dysfunction, acute pandysautonomia should be suspected. In our report, the association with esophageal achalasia is uncommon.

[Carrington's disease without eosinophils in the bronchial lavage]. / Une maladie de Carrington sans éosinophilie au lavage broncho-alvéolaire.

INTRODUCTION: Idiopathic chronic eosinophilic pneumonia (ICEP) or Carrington's disease is an infiltration of the lung parenchyma by eosinophils without known cause. The diagnosis of ICEP is based on well defined clinical and radiological characteristics associated with blood and/or alveolar eosinophilia. Alveolar hypereosinophilia is marked and regarded as a constant feature. CASE REPORT: We report the case of a 57 year old man seen on account of a cough and deterioration of general health associated with radiographic peripheral pulmonary infiltrates, blood hypereosinophilia but no hypereosinophilia in the bronchial lavage (BL). The diagnosis of ICEP was made after histological examination of a surgical lung biopsy. CONCLUSION: Absence of alveolar hypereosinophilia in ICEP remains exceptional and in this case confirmation of the diagnosis may depend on examination of a lung biopsy.

[Necrobiotic xanthogranuloma without monoclonal gammopathy and with a rapidly fatal outcome]. / Xanthogranulome nécrobiotique sans gammapathie monoclonale d'évolution rapidement fatale.

BACKGROUND: Necrobiotic xanthogranuloma is an extremely rare form of histiocytosis that presents clinically as yellowish infiltrated plaques or nodules. Ocular involvement is seen in over 80% of cases. Histopathology reveals numerous xanthomous histiocytes and collagen necrobiosis. Benign monoclonal gammopathy associated with myeloma is found in 80% of patients, but the course is normally long, with 100% survival at 10 years. CASE REPORT: A 76-year-old man presented skin lesions that subsequently became ulcerated. The clinical appearance and histopathological examination resulted in diagnosis of necrobiotic xanthogranuloma. No monoclonal gammopathy or myeloma was seen. The disease was marked by sensitivity to corticosteroids with failure of other therapies (cyclophosphamide, alpha interferon), onset ofcorticosteroid dependency, iatrogenic Cushing's syndrome and diabetes, which were in part responsible for the infectious complications and subsequent death of the patient. DISCUSSION: Necrobiotic xanthogranuloma is difficult to treat, even in the absence of myeloma or monoclonal gammopathy. Corticosteroids are probably the most efficacious treatment, but can give rise to multiple complications, resulting in this particular case in death of the patient.

[An anicteric cholectasis and nephrotic syndrome: AL amyloïdosis in a 51 years-old man]. / Une cholestase anictérique associée à un syndrome néphrotique chez un homme de 51 ans: découverte d'une amylose AL.

Amyloidosis is a multiple-organ disease for which the diagnosis is often confusing and thereby delayed. Here, we present an archetypal case illustrating such difficulties. A 51 years-old man presented a mixed dyslipemia in November 2002, in June 2004 he has finally been diagnosed with a primary AL-amyloidosis. Within these two years, the arising of a non-icteric cholestasis and a nephrotic syndrome have triggered the search for a disease related to a multiple-organ protein deposition. Confirmation of the AL-amyloidosis was obtained through an histological examination, including direct immuno-fluorescence. Amyloidosis is a life threatening disease that need to be diagnosed at an early stage, in order to maximise the therapeutic expectations. The average survival after the diagnosis of AL-amyloidosis is 5% at 10 years. Often, treatments are initiated late in the course of the disease, at a time when organ lesion are constituted, severely affecting the prognosis.

[Recurrent Castleman's disease of the neck occurring in an infant]. / Maladie de Castleman cervicale récidivante chez un nourrisson.

INTRODUCTION: Castleman's disease is a lympho-proliferative disease of unknown cause. This rare disease, usually localized, is benign and develops in the young adult. The predominant localization is mediastinal. OBSERVATION: A 15 month-old infant was referred for a left latero-cervical mass that had developed since the age of 3 months. Other than this, the clinical examination was normal. Sonography, x-ray and tomodensitometry confirmed the unique nature of the lesion and the absence of loco-regional invasion. Histology following surgical exeresis found a nodule with multiple pseudo-follicular structures. These mitosis-rich structures were arranged concentrically around a vessel and were bordered by small lymphocytes forming a crown. This histological aspect corresponded to Castleman's disease in its vascular hyaline form. Local recurrence was reported twice, 2 and 8 years later and was treated each time with surgical exeresis. Histological examination was always similar to the first. DISCUSSION: Castleman's disease has rarely been reported in infants. The cervical location, at whatever age, is far rarer than the mediastinal form. Supplementary examinations are not always of interest and basically provide information on the isolated or multicentric nature. Surgical exeresis was justified because of the diagnostic doubts and the risk of compression. Diagnosis is based on anatomopathology. Relapses have rarely been described in the literature and raise the question of the potential malignant transformation after several relapses.

[Generalized granuloma annulare: remission during treatment of HIV infection]. / Granulome annulaire généralisé: guérison au cours du traitement d'une infection par le VIH.

INTRODUCTION: Granuloma annulare is a benign dermatosis characterized by pale or erythematous papules grouped in rings or in arch form figures. We report the observation combining a granuloma annulare and a Human Immunodeficiency Virus (HIV) infection, with regression of the granuloma annulare on initiation of treatment of the HIV infection. OBSERVATION: A 33 year-old man presented with an eruption of multiple, erythematous papules predominating on the trunk and limbs but sparing the face. Histology confirmed the diagnosis of generalized granuloma annulare. We diagnosed an HIV infection. Remission of the granuloma annulare was obtained concomitantly when immune restoration was obtained following the prescription of an antiretroviral tritherapy. DISCUSSION: Since 1985, several cases of atypical forms of granuloma annulare have been reported in HIV-infected patients. Nevertheless, the precise relationship between the two diseases is unknown. The case we report on raises the question of the relationship between granuloma annulare and immunodepression.

[Paraneoplastic pemphigus revealing dendritic cell sarcoma originating from Castleman's disease of the neck]. / Pemphigus paranéoplasique révélateur du développement d'un sarcome à cellules dendritiques à partir d'une tumeur de Castleman pulmonaire.

INTRODUCTION: Paraneoplastic pemphigus is associated with Castleman's disease. We report a case of paraneoplastic pemphigus at the stage of the sarcomatous transformation of Castleman's disease, present for many years but without concomitant paraneoplastic pemphigus. The pemphigus was manifested by the most unusual, exclusive, involvement of the mucosa of the mouth and lung. OBSERVATION: A 32 year-old man suffering from extensive ulceration of the oral mucosa was hospitalized in December 2000 for alteration in his general status of health and acute respiratory failure. The search for intercellular anti-substance antibodies on rat spleen was positive, corresponding to anti-envoplakin IgG and leading to the diagnosis of paraneoplastic pemphigus. The thoracic x-ray and scan revealed a hilum tumor, the histological examination of which confirmed the diagnosis of Castleman's disease concomitant to sarcomatous transformation. Following surgical treatment, the respiratory failure worsened. The patient improved with systemic corticosteroids at the dose of 2 mg/kg/d and chemotherapy was initiated. The patient died suddenly within the context of acute respiratory failure, three months after surgery. DISCUSSION: This is a case of paraneoplastic pemphigus of unusual clinical and biological expression: exclusively mucosal involvement with obliterating bronchiolitis, explained by the isolated presence of antibodies recognizing envoplakin, without anti-desmoglein. The transformation of the Castleman tumor into a sarcoma may have unmasked intra-cellular antigens (plakins), initiating the specific immune reaction.

Pulmonary manifestations revealing Rosai-Dorfman disease.

Rosai-Dorfman disease is a rare non-Langerhans cell histiocytosis, mainly involving cervical nodes. We present the case of a patient with a pulmonary form of Rosai-Dorfman disease without peripheral or intra-thoracic lymph nodes, characterized by the presence of pulmonary nodules and cysts associated with bilateral pleural effusions.

Preoperative radiotherapy (RT) for rectal cancer: predictive factors of tumor downstaging and residual tumor cell density (RTCD): prognostic implications.

PURPOSE: To determine predictive factors and prognostic value of tumor downstaging and tumor sterilization after preoperative RT for rectal cancer. METHODS AND MATERIALS: Between 1977 and 1994, 167 patients with a histologically proven adenocarcinoma (70 T2, 65 T3, 29 T4, and 3 local recurrences) underwent preoperative RT. Median dose was 44 Gy (5-73 Gy). Surgery was performed in a mean time of 5 weeks after RT. Pathologic specimens have been reviewed by the same pathologist in order to specify the modified Astler Coller classification (MAC), and to quantify the residual tumor cell density (RTCD). RESULTS: According to the MAC, there was 9 stage 0 (5%), 10 stage A (6%), 103 stage B1-B3 (62%), and 45 stage C1-C3 (27%) tumors. Seventeen percent and 56% of the patients who received a dose > or = 44 Gy had respectively a 0-A and a B tumor, compared to 4 and 69% in those who received a dose < 44 Gy (p = 0.04). Tumor differentiation and a longer interval before surgery were significantly associated with a more frequent downstaging, and preoperative staging correlated well to the postoperative pathological findings. According to the RTCD, 62 tumors (37%) showed no or only rare foci of residual tumor cells (Group 1); 62 (37%) showed an intermediate RTCD (Group 2); and 43 (26%) a high RTCD (Group 3). No predictive factor of RTCD was statistically significant. In univariate analysis, postoperative staging was a significant prognostic factor, with corresponding 5-year overall survival rates in 0-A, B, and C stages of 92, 67, and 26% (p < 0.01). RTCD was not a prognostic factor. However, overall and disease-free survival rates for patients with complete pathologic response of 83% at 2 and 5 years suggested a better outcome in this subgroup of patients. CONCLUSION: The favorable influence of higher doses of preoperative RT on pathologic stage has been observed. Tumor differentiation, preoperative classification and time before surgery were the other predictive factors of tumor downstaging. However, there was no predictive factor of complete pathologic response. Even after preoperative RT, postoperative staging remained a prognostic factor.

Relevance of vertical growth pattern in thin level II cutaneous superficial spreading melanomas.

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Statistical evaluation of diagnostic and prognostic features of CD30+ cutaneous lymphoproliferative disorders: a clinicopathologic study of 65 cases.

Several clinical and histopathologic features of 65 CD30+ cutaneous lymphoproliferations were evaluated for their diagnostic value between CD30+ primary versus secondary cutaneous lymphomas and for their prognostic significance. Primary cutaneous disease, spontaneous regression, and absence of extracutaneous spreading (but not age < or =60 years) were associated with a better prognosis. Epithelial membrane antigen, BNH9, CD15 or CBF.78 antigen were expressed in all types of cutaneous lymphoproliferations. However, epithelial membrane antigen immunoreactivity was more frequently expressed in CD30+ secondary cutaneous large-cell lymphoma. Among CD30+ primary cutaneous large-cell lymphoma, CD15 expression was only seen in localized skin lesions. P53 expression was not associated with spontaneous regression, extracutaneous spreading, or survival. Nested reverse transcriptase-polymerase chain reaction allowed the detection of NPM-ALK transcripts in 10 of 26 CD30+ primary and in 3 of 11 secondary cutaneous large-cell lymphomas. The ALK protein was detected in only 1 of 50 primary and in 4 of 15 secondary cutaneous CD30+ lymphoproliferations. In CD30+ primary cutaneous lymphoproliferation, NPM-ALK transcripts might be expressed by very rare normal or tumoral cells that are undetectable by immunohistochemistry. However, the expression of either NPM-ALK transcripts or ALK-protein was not correlated with prognosis or age in CD30+ cutaneous lymphoproliferations.

Calcifying fibrous pseudotumor of the mediastinum.

Calcifying fibrous pseudotumor has recently been described in the soft tissues. It is a rare benign lesion characterized by the presence of abundant hyalinized collagen with psammomatous or dystrophic calcifications and lymphoplasmacytic infiltrate. We report a case of a young woman with a mediastinal mass treated by a complete resection. The mass had all the pathologic features of calcifying fibrous pseudotumor.