Combined renal proximal tubulopathy and crystal storing histiocytosis in a patient with κ light chain multiple myeloma.

Multiple myeloma accounts for 10-15% of all hematologic malignancies, and 20% of deaths related to cancers of the blood and bone marrow. Diagnosis is defined by the presence of a serum monoclonal spike (M-spike) of more than 3 g/dL or more than 10% clonal plasma cells in the bone marrow and at least one myeloma-defining event, such as hypercalcemia, anemia, bone lesions, or renal impairment. The kidney is a major target organ, and renal impairment is frequently the first manifestation of the disease. Renal damage occurs in up to 40% of patients and 10-20% will require dialysis. Monoclonal immunoglobulin light chains are the major causes of renal complications in multiple myeloma. Glomerular disease, with the deposition of monoclonal immunoglobulins or their components, includes monoclonal immunoglobulin deposition disease, AL or AH amyloidosis, type I cryoglobulinemia, proliferative glomerulonephritis with monoclonal IgG deposits, immunotactoid glomerulopathy, and fibrillary glomerulonephritis. In addition, tubulointerstitial diseases with the deposition of monoclonal immunoglobulins or their components, are constituted by light chain cast nephropathy, light chain proximal tubulopathy, and crystal-storing histiocytosis.We report the case of a 66-year-old woman who presented with albumin-predominant moderate proteinuria and renal failure. Serum and urine immunofixation electrophoresis showed monoclonal κ light chain in both. Renal biopsy confirmed κ-restricted crystal-storing renal disease involving proximal tubular epithelial cells and crystal storing histiocytosis. Multiple myeloma with crystal storing histiocytosis was discovered in bone marrow biopsy. Thus, we present an unusual case of a myeloma patient presenting light chain proximal tubulopathy and crystal-storing histiocytosis both in the kidney and in the bone marrow.

Acute Generalized Exanthematous Pustulosis (AGEP) in 12 Patients Treated for SARS-CoV-2 Positive Pneumonia.

ABSTRACT: The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rapidly spreading throughout the world. The study describes 12 patients with SARS-CoV-2 pneumonia, who developed an acute erythematous rash with nonfollicular pinhead-sized pustules, without mucosal involvement. The clinical differential diagnosis was viral rash, acute generalized exanthematous pustulosis (AGEP), or multiform erythema. computed tomography with a diagnosis of interstitial pneumonia and a respiratory tract sample positive for SARS-CoV-2 in a reverse transcriptase polymerase chain reaction assay. Patients had signs of respiratory distress and were treated with hydroxychloroquine, darunavir, ritonavir, heparin, ceftriaxone, and azithromycin. Punch biopsies showed subcorneal pustules typical of AGEP. Dermal microvascular injury and thrombosis as described in skin damage by SARS-CoV-2 infection was not observed. The direct immunofluorescence for IgG, IgA, IgM, and C3 was negative in 8 patients investigated. A polymerase chain reaction for RNA SARS-CoV-2 performed on frozen skin was negative in 5 of 6 patients. Most of our patients were treated with systemic corticosteroids. After some days (4-10), the diffuse erythema and pustules had improved. AGEP is classified as a severe cutaneous adverse reaction, provoked by drugs and acute infections. Characteristically, removal of the offending agent leads to spontaneous resolution typically in less than 15 days. The recognition of AGEP is important, in order to avoid confusion with a systemic infection and consequently to avoid incorrect treatment. Cutaneous adverse reactions to drugs are common and are major health problems worldwide causing considerable costs for health care systems. We suggest that in the patients with AGEP during SARS-CoV-2 pneumonia, viral infection is a risk factor for developing drug reaction.

Congenital Unilesional Cutaneous Langerhans Cell Histiocytosis: A Case Report.

ABSTRACT: Langerhans cell histiocytosis (LCH) is a clonal proliferation of bone-marrow-derived cells, which normally reside as epidermal and mucosal dendritic cells involved in antigen presentation. It is a rare disease more common in children than adults, that is believed to be neoplastic in most cases. The diagnosis is based on clinical and radiological findings in combination with histopathologic, immunophenotypic, or ultrastructural analyses. LCH have a broad spectrum of clinical manifestations, ranging from benign cutaneous lesions to malignant multisystem disease. Based on the extent of involvement at diagnosis, LCH can be divided in single-system LCH when only one organ or system is involved, usually with multiple lesions, and multisystem LCH, when 2 or more organs or systems are involved at diagnosis. One variant of LCH is characterized by congenital isolated cutaneous involvement. It typically manifests at birth or in the postnatal period with a widespread eruption of red-to-brown papulo-nodules or, more uncommonly, a solitary lesion. The overall prognosis for single lesion skin limited LCH is excellent and most lesions spontaneously resolve within 4-18 weeks. Systemic involvement is rare. Skin findings cannot predict systemic disease and obtaining an oncology consultation is recommended for further evaluation. Herein, we present an additional case in a full-term, well-appearing, female infant with an isolated, asymptomatic, ulcerated, papule of the left arm, that was noted at birth.

NeuN, a DNA-binding neuron-specific protein expressed by Merkel cell carcinoma: analysis of 15 cases.

AIM: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma, with an increasing worldwide incidence. It presents as a painless red to purple nodule on sun-exposed skin. MCC is presumed to arise from resident cutaneous Merkel cells. The pathogenesis of MCC is likely multifactorial with immunosuppression, UV-induced skin damage, and Merkel cell polyomavirus contributing to the development. The diagnosis of MCC relies upon characteristic morphologic features and use of immunohistochemical stains. Histologically, the differential diagnosis of Merkel cell carcinoma includes the 'small round cell' tumor group, particularly metastatic small cell carcinoma and hematological malignancies. This study investigates the expression of NeuN antibody, which recognizes the protein NeuN, normally present in most neuronal cell types and neuronal tumors, in Merkel cell carcinomas. METHODS AND RESULTS: Fifteen cases of Merkel cell carcinoma (7 men and 7 women; mean age 74 years) were retrieved from the institute database between the years 2011-2020. The immunohistochemical profile was investigated: CK20 (14/14), Neurofilament, (12/12), Synaptophysin (14/14); Chromogranin A (11/13), PAX5 (10/12), TDT (5/12), CK7 (1/14), TTF1 (0/14). Infection by Polyoma virus was detected in 11 of 14 patients. Most tumors showed middle/strong expression of NeuN. No cutaneous structures, or epidermal Merkel cells, showed expression of NeuN. The expression of NeuN was investigated in 17 primary small cell lung carcinomas: 2 cases were positive for Neu-N. CONCLUSIONS: Awareness of the staining pattern of Neu-N could aid in diagnosis of Merkel cell carcinoma, avoiding misinterpretation and erroneous diagnosis with other tumors.

A case of trichogerminoma: a rare cutaneous follicular neoplasm.

Trichogerminoma, first described by Sau et al. in 1992, is a rare cutaneous adnexal neoplasm of the hair germ cell and usually associated with benign clinical course and favorable outcome. About 30 cases have been reported, all with similar histological features. However, due to a small but potential risk of malignancy, complete excision of the tumor is the treatment of choice. There is still controversy over its inclusion into the spectrum of trichoblastoma.Herein, we report an additional case occurring in the left buttock of a 47-year-old female, presenting with a subcutaneous solitary nodule composed of lobules of basaloid cells, with peripheral palisading and round cell nests or "cell balls" arranged in the central part. The lobules are separated by a fibrous or myxoid stroma. There are no clefts separating the tumor cells and surrounding stroma, but clefts separating stroma by the surrounding adipose tissue can be seen. Typical mitotic figures are frequently present (4-5 per 10 high-power fields). Immunohistochemistry shows the tumor cells are positive for pan-CK (AE1/AE3), CK5/6, p40, GATA 3, whereas they are negative for CK7, CK20, chromogranin A, synaptofisin, androgen receptor, estrogen receptor, and calretinin. Staining for CK20, synaptofisin, and chromogranin A detect Merkel cells scattered within the lobules. Ki67 highlights a nuclear proliferative rate of about 20%.Trichogerminoma should be distinguished from other trichogenic tumors made up of basoloid cells or hair follicular differentiation. The mainly differential diagnosis includes trichoblastoma, trichoepitelioma, tricholemmoma, and basal cell carcinoma.Herein, we report a case of trichogerminoma which, unlike the cases previously reported, showed numerous mitotic figures and a higher Ki67 nuclear proliferative rate.

Langerhans cell histiocytosis of an intra-mammary lymph node in an 18-year-old woman.

We describe an 18-year-old woman with several month's history of a 12 x 7 mm palpable mammary nodule, that was hypoechoic, with regular margins and vascularization areas by ultrasound. A fibroadenoma was hypothesized (American College of Radiology BI-RADS 3). A 14 G needle biopsy was performed, showing a LC proliferation suspected for LCH of a lymph node, with florid dermatopathic lymphadenopathy in differential diagnosis. The multidisciplinary team of the breast clinic decided to perform a lumpectomy and a diagnosis of LCH involving an intra-mammary lymph node was made. Langerhans cells (LC) are dendritic cells characterized by grooved nuclei, irregular nuclear contours, and abundant cytoplasm, that normally reside in the skin and mucosal surfaces. They were positive for CD1a, langerin/CD207, and S100 by immunohistochemistry. Langerhans cell histiocytosis (LCH) is a clonal proliferation of histiocytes that is thought to be neoplastic in most cases. Reactive LC can be distinguished from LCH by cyclin D1 immunostaining, which is positive only in LCH. About 50% of cases have BRAF V600E mutations. The revised classification of histiocytes divides LCH in subtypes: LCH SS (single system), LCH lung positive, LCH Multiple System/Risk Organ negative and LCH Multiple System/Risk Organ positive. Localized disease can progress to multisystem involvement. The diagnosis of LCH is based on clinical and radiological findings in combination with histopathological, immunophenotypic or ultrastructural analyses identifying tissue infiltration by LC. It is recommended that biopsy confirmation of suspected LCH be performed in all cases. Lymph nodes may be the only site of disease or a part of multisystem involvement by LCH. The histologic differential diagnosis is discussed.

Microsatellite Instability in Medullary Carcinoma of the Colon.

Medullary carcinoma (MC) of the large intestine is a relatively new histological type of adenocarcinoma characterized by poor glandular differentiation and an intraepithelial lymphocytic infiltrate. MC can be associated to a defective mechanism for DNA mismatch repair, caused by the so-called microsatellite instability (MSI). We present the case of a 44 years old Caucasian woman, who referred to the Emergency Room with symptoms mimicking an acute appendicitis. Computed tomography and colonoscopy demonstrated an ulcerated and stenotic lesion of the caecum without signs of metastasis and peritoneal carcinosis. Patient underwent a laparoscopic right colectomy. The final pathologic findings provided the diagnosis of medullary carcinoma with MSI. Patient then underwent adjuvant chemotherapy according to the FOLFOX-4 protocol (association of 5-Fluorouracil, Leucovorin, and Oxaliplatin) for twelve cycles. At two-years follow-up, patient is disease free. MC in association with MSI is a non-frequent tumor of the colon characterized by a better prognosis compared to other types of poorly differentiated adenocarcinoma. In the observed case, 24 months after the surgical operation, the patient is in good health and there is no evidence of metastasis or relapse.