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.

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.

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.

[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.

[Myoepithelial carcinoma of the lacrimal gland]. / Le carcinome myoépithélial de la glande lacrymale.

INTRODUCTION: Myoepithelial carcinomas are unusual tumors most often located in salivary glands. It is very rarely located in lacrimal glands; only 5 cases have been reported. We report a sixth case. OBSERVATION: An 88-year-old male patient presented with diplopia, painless right sided exophthalmia, as well as eyeball deviation due to a tumor located at upper external quadrant of the orbit. A biopsy initially suggested a sarcoma. The pathological analysis of the biopsy allowed diagnosing a myoepithelial carcinoma of the lacrimal gland. Despite the monoblock resection of the tumor, a recurrence was observed 3 months after removal. The patient died 8 months after the initial surgery. DISCUSSION: This case illustrates the clinical and pathological characteristics of a myoepithelial carcinoma. This tumor has a high grade of malignancy, and is very rarely described in lacrimal glands. The morphological diagnosis of this tumor is difficult with a problematic differential diagnosis with fusiform cells sarcomas (leiomyosarcoma, undifferentiated sarcoma), and epithelial-myoepithelial carcinoma.

[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.

Chronic bronchiolitis in ankylosing spondylitis.

The pleuro-pulmonary signs of ankylosing spondylitis are generally asymptomatic, typically represented by biapical lung fibrosis. To our knowledge, the severe bronchiolitis which is sometimes observed in other spondyloarthropathies has not been described in ankylosing spondylitis. We report two cases of severe chronic bronchiolitis in ankylosing spondylitis patients. Their clinical and radiological presentation were similar, characterized by progressive deterioration of stage III-IV dyspnea, non-reversible obstructive ventilatory defect, and CT scan showing air trapping with mosaic attenuation and ground-glass opacity in expiration. Lung biopsies confirmed the diagnosis of severe follicular bronchiolitis in one patient and constrictive bronchiolitis is suspected in the other. Only the patient with follicular bronchiolitis responded positively to treatment with low doses of macrolides.

[Extremely rapid progression of oral cavity carcinosarcoma]. / L'évolution extrêmement rapide d'un carcinosarcome de la cavité orale.

INTRODUCTION: Carcinosarcoma is a very rare malignant tumor of the salivary glands including accessory salivary gland, associating malignant mesenchymal and epithelial tissue. It usually occurs after 50 years of age. Its prognosis is very poor. We present a case of carcinosarcoma having evolved extremely rapidly. CASE REPORT: A 38-year-old female patient presented with an inflammatory budding lesion of the mandibular gingival mucosa. The diagnosis of carcinosarcoma having developed from an accessory salivary gland was made after testing biopsies. The carcinosarcoma could not be removed because of an extremely rapid tumor growth, its volume having increased three fold in 2 weeks. The patient died in a few weeks. DISCUSSION: The occurrence of carcinosarcoma at 38 years of age is exceptionally rare. The rapidly evolution of carcinosarcoma is well documented. It may prevent complete excision. This case led us to suggest an emergency management for carcinosarcomas.

Eumycetoma of the foot caused by Exophiala jeanselmei in a Guinean woman.

Eumycetomas are chronic infectious entities characterized by presence of mycotic grains in (sub-)cutaneous tissues, after accidental inoculation of an exogenous filamentous fungus in the skin. The lesions evolve towards painless pseudotumor of the soft parts. We report the original case of a Guinean woman exhibiting eumycetoma of the right foot. Both laboratory tests identified a dematiaceous fungus, Exophiala jeanselmei, as the responsible infectious agent. A medical treatment with voriconazole alone was sufficient to notice a substantial clinical improvement. This finding is unusual as E. jeanselmei is uncommon in Guinea-Conakry, and as optimal treatment rather associate antifungal azoles and surgical excision.

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.

Organising pneumonia can be the inaugural manifestation in connective tissue diseases, including Sjogren's syndrome.

Connective tissue diseases are known to be one of the causes of organising pneumonia (OP). However, this association is rare and signs of OP usually occur in the context of an already diagnosed disease. We report three cases of OP preceding the articular symptoms of the underlying connective tissue disease by 3-6 months in two cases of rheumatoid arthritis and by 36 months in one patient with primary Sjögren's syndrome. The diagnosis of post-infectious OP had initially been suspected in the three cases and the patients had not been followed up further. The occurrence of OP preceding articular or any other extrapulmonary involvement of connective tissue disease had been reported in only four cases in the literature and, to our knowledge, no case preceding Sjögren's syndrome had ever been reported. These observations suggest that exhaustive investigations should be considered when OP is diagnosed, including antinuclear auto-antibodies and investigations for Sjögren's syndrome, even when there are no clinical signs suggesting an underlying connective tissue disease. These investigations should also be repeated during the course of the disease, especially in the case of OP continuing to progress under treatment and, of course, if signs of connective tissue disease appear.

[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.

Hepatitis B virus reactivation after a resolutive acute hepatitis leading to a diagnosis of T cell lymphoma.

A case of hepatitis B virus reactivation leading to the diagnosis of a T cell lymphoma is reported. A 66-year-old woman with a past history (10 years before) of spontaneously recovered acute hepatitis B (with disappearance of serum hepatitis B surface antigen and appearance of anti-HBs), has been referred for hepatologic consultation for acute hepatitis. The patient was found positive again for hepatitis B surface antigen as well HBeAg and hepatitis B virus DNA. No other cause of liver disease was identified and a diagnosis of spontaneous hepatitis B virus reactivation was made. Five months later a peripheral T cell lymphoma was diagnosed. This unusual case confirms that natural immunity is not protective against hepatitis B virus reactivation and shows that such hepatitis B virus reactivation may precede the usual clinical manifestations of a peripheral T cell lymphoma.

[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.