[Enlarged mediastinal lymph nodes of a patient with malignant melanoma stage IV under pembrolizumab treatment]. / Mediastinale Lymphknotenvergrößerung bei einer Patientin mit malignem Melanom Stadium IV unter Therapie mit Pembrolizumab.

A 40-year-old patient with malignant melanoma pT4bN0M1a stage IV (AJCC classification 2017) was treated with the PD-1/PD-L1 antibody pembrolizumab. Three months after treatment initiation the patient developed enlarged mediastinal lymph nodes despite the partial response of the cutaneous metastases. An elective lymph node extirpation was performed. The histopathological result was consistent with a sarcoid-like reaction. Treatment was discontinued and a pulse therapy with systemic steroids led to a significant remission of the lymphadenopathy. This side effect can manifest both during PD-1/PD-L1 antibody and CTLA-4 antibody therapy and should be included in the differential diagnosis of mediastinal lymphadenopathy.

IgG4-related membranous glomerulonephritis and generalized lymphadenopathy without pancreatitis: a case report.

BACKGROUND: IgG4-related disease is a recently described pathologic entity. This is the case of a patient with nephrotic syndrome and lymphadenopathy due to IgG4-related disease. Such a kidney involvement is quite peculiar and has only been described a few times recently. Renal biopsy showed a glomerular involvement with membranous glomerulonephritis in association with a tubulo-interstitial nephropathy. Moreover, the patient was not suffering from pancreatitis. CASE PRESENTATION: The patient is a middle-aged man of Moroccan origin. He has developed recurrent episodes of diffuse lymphadenopathies, renal failure and nephrotic syndrome. Renal biopsies showed membranous glomerulonephritis. DISCUSSION AND CONCLUSION: The diagnostic approach of this atypical presentation is discussed in this case report as well as diagnostic criteria, therapeutic strategies, biomarkers and pathophysiology of IgG4-related disease. IgG4-related membranous glomerulonephritis is a well-established cause of membranous glomerulonephritis. It must be sought after in every patient with a previous diagnosis of IgG4-related disease and in every patient with this histological finding on renal biopsy. Corticoids are still the first-line treatment of IgG4-related disease. New therapeutic strategies are needed to avoid glucocorticoids long term side-effects. Interestingly, the patient was prescribed cyclophosphamide in addition to glucocorticoids for an immune thrombocytopenia. This treatment had a very good impact on his IgG4-related disease.

Pattern and predictors of paradoxical response in patients with peripheral lymph node tuberculosis.

INTRODUCTION: Many of the patients with lymph node tuberculosis show 'Paradoxical Response" in the form of appearance of new lymph node (LN) or increase in the size of existing LN, development of new disease in other organ and worsening of the disease while on treatment. Reason behind such response in only selective patients is not clearly understood. We evaluated the pattern and predictors for paradoxical response(s) (PR) in patients with peripheral lymph node tuberculosis (TB). MATERIALS AND METHODS: Study included patients aged > 6 years with peripheral lymphadenopathy of tubercular etiology attending a tertiary care hospital from Jan 2010 to Dec 2010. PR in our study was defined as worsening of pre-existing disease or development of new lesions in a patient who has been on anti-TB therapy for at least 2 weeks. RESULT: One hundred ten patients with peripheral lymph node TB were included. Their mean age was 27.5 ± 5 years and 68 (62%) were females. PR occurred in 28 (25%) patients, at a mean onset time of 6 weeks (range 2-12 weeks) after starting anti-TB medication. Four of these 28 patients experienced PR on two occasions. Of these, 22 (79%) patients presented with enlarged lymph nodes only, 8 (29%) with new nodes at same or different site and 2 (7%) with discharging sinus. PR was observed more in younger age group (p> 0.05), female gender (p> 0.05), unilateral lymphadenopathy (p> 0.05) and those with positive AFB on initial examination (p< 0.01). CONCLUSIONS: Paradoxical response in peripheral lymph node TB is associated with younger age, female gender, unilateral lymphadenopathy and those with positive AFB on initial examination.

Adult-onset Periodic Fever, Aphthous Stomatitis, Pharyngitis and Cervical Adenitis Syndrome Responsive to Colchicine.

We herein report a rare case of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome that occurred in an 18-year-old man. He visited our hospital with recurrent episodes of a fever, pharyngitis and adenitis without suggestive findings of infection. These episodes resolved within 5 days and recurred quite regularly, with an interval of about 30 days. As the febrile episodes significantly impaired his quality of life, he was treated with colchicine (0.5 mg) as prophylaxis. This completely prevented the episodes during six months of follow-up. Colchicine may therefore be effective in cases of adult-onset PFAPA syndrome.

Xeloda Oral, Trastuzumab, and Pertuzumab Combined Drug Therapy Reduced Cervical Lymphadenopathy and Dermal Involvement in Patient With Recurrent Breast Cancer: Case Report.

We report the case of a 42-year-old woman who was diagnosed with breast cancer that recurred 3 years later, with supraclavicular lymphadenopathy and dermal involvement. The main drug used in the therapy was trastuzumab; however, the association of this drug with docetaxel was not able to decrease or cease the effect of the inflammatory BCA component with erythema and thickening of the skin as well as the supraclavicular lymphadenopathy previously diagnosed. Thus, a combined therapy was required. The patient was started on 6 cycles (1 per month) of trastuzumab subcutaneous 600 mg, pertuzumab intravenous 840 mg (as an attack dose, later on 420 mg), and xeloda oral 1000 mg. As a result, the patient showed a significant improvement in erythema and thickening of the skin in the neck and the right part of her trunk, besides decrease in supraclavicular lymphadenopathy. After 6 cycles, her skin was almost restored. Intravenous trastuzumab can be an effective single agent; however, its association with other chemotherapies-such as pertuzumab-can present a synergic effect, which can increase the survival expectations of metastatic HER2+ patients. Additionally, as reported in the literature, the use of xeloda plays a key role in restoring the skin health of patients with breast cancer presenting with skin metastasis. Our findings suggest that trastuzumab, pertuzumab, and xeloda combined therapy, following the schedule and posology handled in this study, can be a good treatment for recurrent HER2+ breast cancer with signs of supraclavicular lymphadenopathy and severe inflammatory BCA component with erythema and thickening of the skin.

Histopathology of thymectomy specimens from the MGTX-trial: Entropy analysis as strategy to quantify spatial heterogeneity of lymphoid follicle and fat distribution.

The thymectomy specimens from the "thymectomy trial in non-thymomatous myasthenia gravis patients receiving prednisone therapy" (MGTX) underwent rigid and comprehensive work-up, which permits analysis of the spatial distribution of histological and immunohistological features. This analysis revealed strong intra- and inter-case variability. While many histological features (e.g. median percent fat content among different specimens) can easily be correlated with clinical parameters, intra-case spatial variability of histological features has yet defied quantification and statistical evaluation. To overcome this gap in digital pathology, we here propose intra-case entropy of measured histological features in all available slides of a given thymectomy specimen as a quantitative marker of spatial histological heterogeneity. Calculation of entropy led to one value per specimen and histological feature. Through these 'entropy values' the so far neglected degree of spatial histological heterogeneity could be fed into statistical analyses, extending the scope of clinico-pathological correlations.

Successful treatment by rituximab in a patient with TAFRO syndrome with cardiomyopathy.

  TAFRO syndrome is a newly defined disease entity which is characterized by thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly. A histological pattern of multiple lymphadenopathy of atypical Castleman's disease (CD) is also an important characteristic. A 48-year-old man was referred to our hospital with fever, asthenia, bilateral pleural effusion, ascites, generalized edema, dyspnea, hypoalbuminemia, severe thrombocytopenia, anemia, renal failure and proteinuria, whereas bacterial culture and serological and PCR tests for various viruses were all negative. A CT scan showed multiple lymphadenopathy and tissue sampling of inguinal lymph nodes showed a compatible histology with plasma cell type CD. A diagnosis of TAFRO syndrome was made. Ten days after hospitalization, sudden cardiac insufficiency and anuria developed. Despite glucocorticoid pulse therapy, tocilizumab and plasmapheresis, clinical and laboratory features did not improve. On the 34(th) hospital day, we started rituximab. His general condition started to improve in several days, and by one month later anasarca had improved drastically. Thrombocytopenia and renal function gradually improved and finally normalized. Cardiac motion also improved. This is the first report of a TAFRO syndrome patient with cardiomyopathy, who was successfully treated with rituximab.