U.O. Anatomia Patologica I

We evaluated by immunohistochemistry the expression of the Bcl-2 and p53 proteins, as markers of apoptosis control, and of MIB-1, as a marker of cell proliferation, in a series of normal and neoplastic adrenocortical tissues. The specimens were 13 normal adrenals, 13 aldosterone-producing adenomas, 13 non-functioning adenomas and 16 carcinomas. Results were calculated as percentage of immunostained cells by using specific antibodies. No p53 protein was detected in any of the adrenocortical adenomas (functioning and non functioning) or normal adrenals, while p53 was overexpressed in 15 out of 16 carcinomas. In particular, 10 adrenal cancer specimens (62.5%) showed strong staining in a high percentage (range 10-50%) of the malignant cells. The percentage of Bcl-2 positive cells was higher (P<0.05 or less) in non-functioning adenomas (8.1+/-1.9%) and in carcinomas (14.9+/-5.6%) than in normals (2.9+/-0.9%) and aldosterone-producing adenomas (5.3+/-1.3%) since four specimens of the n...

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and clinically aggressive haematologic malignancy caused by neoplastic transformation and clonal proliferation of plasmacytoid dendritic cell precursors. Current treatment approaches are not effective and the outcome remains poor in the majority of patients even after chemotherapy and bone marrow transplantation. In this report we consider the use of interferon alpha for old unfit patients not candidate for intensive strategies.

PATOLOGIA DELL’OSSO E TESSUTI
MOLLI
CIC-DUX4 UNDIFFERENTIATED SMALL ROUND CELL
SARCOMA: REPORT OF A CASE
A.G. Bonadio1, R. Capanna2, M. Gambarotti3, S. Benini3, A.
Franchi4
1 U.O. Anatomia Patologica I Pisa; 2 U.O. Ortopedia 2 Pisa; 3 Anatomia
Patologica, Istituti Ortopedici Rizzoli, Bologna; 4 Dipartimento di
Chirurgia e Medicina Traslazionale, Università di Firenze
Introduction. CIC-DUX4 undifferentiated sarcomas are a
group of EWSR1- negative primitive tumors or Ewinglike
sarcomas with fusion of the human homologue of the
Drosophila capicua (CIC) gene on chromosome 19 and the
double-homebox 4 (DUX4) retrogene on chromosome 4 or
10. The vast majority of these sarcomas occur primarily in
peripheral soft tissues, but rare bone and visceral cases have
been reported 1-3.
Materials and methods. Here we report a case of CIC-DUX4
undifferentiated small cell sarcoma (USCS) in a 26 year old man
involving the soft tissues of left forefoot, between the IV and V
finger.
Results. Macroscopically, the lesion was grey, with areas
of necrosis, measured about 3 cm and was localized in the
subcutis. On hematoxylin and eosin sections, a round cell
component predominated, which was focally set in a myxoid
stroma. Foci of hemangiopericytoma-like vascular growth
pattern and mitoses were present. Immunoistochemically,
tumor cells were weakly positive for CD99, diffusely positive
for WT1 and cytokeratins (Cam 5.2 and AE1/AE3), while
chromogranin, synaptofisin, S100, HMB45, Mart1, calponin,
p63, CD45, TdT, myogenin, desmin and smooth muscle actin
were negative. Upon fluorescent in situ hybridization (FISH)
analysis, CIC gene rearrangement was identified, while SYT
rearrangement was absent.
Discussion. Recently, a distinct CIC-DUX4 fusion derived
from a novel translocation of t(4;19) (q35;q13) has been
detected in some of the Ewing-like sarcomas, and CICDUX4
fusion sarcoma has been established as a new type of
Ewing-like sarcoma. The tumor tends to affect children and
young adults and involves mainly the soft tissues of the trunk
and extremities. Clinicopathologic studies of large series of
CIC-DUX4 sarcomas have not yet been performed because
of its rarity. However, it has been reported that patients with
CIC-DUX4 sarcoma tend to experience an aggressive clinical
course and poor outcome. The diffuse immunohistochemical
staining for cytokeratins observed in this case represents a
potential a diagnostic pitfall.
References
1 Choi EY, Thomas DG, McHugh JB, Patel RM, Roulston D, Schuetze
SM, Chugh R, Biermann JS, Lucas DR. Undifferentiated small round
cell sarcoma with t(4;19)(q35;q13.1) CIC-DUX4 fusion: a novel
highly aggressive soft tissue tumor with distinctive histopathology.
Am J Surg Pathol. 2013;37:1379-86.
2 Antonescu C. Round cell sarcomas beyond Ewing: emerging entities.
Histopathology. 2014;64:26-37.
3 Gambarotti M, Benini S, Gamberi G, Cocchi S, Palmerini E, Sbaraglia
M, Donati D, Picci P, Vanel D, Ferrari S, Righi A, Dei Tos AP. CICDUX4
Fusion-Positive Round Cell Sarcomas of soft tissue and bone:
a single institution morphologic and molecular analysis of 7 cases.
Histopathology. 2016 Apr 15. doi: 10.1111/his.12985

In this report, we describe a case of poorly differentiate myoepithelial cell rich carcinoma in with morphological findings of large poligonal nests with festoonlike pattern sometimes showing central necrosis, reminiscent of a comedo-like pattern and numerous mitoses. Immunohistochemical staining shows positive reaction for cytokeratin AE/1, CAM 5.2, 34 beta E12, vimentin, smooth muscle actin, EMA, S100 protein and oncogene cERB.b2 and negative for estrogen, progesterone, GFAP and chromogranin. Moreover, this carcinoma show the expression of the mammaglobin mRNA, a highly specific marker of breast epithelial cells that it is not expressed in all breast carcinoma.

Ultrasound-guided fine needle aspiration cytology (FNAC) of suspect parathyroid adenomas is sometimes used for the diagnosis of primary hyperparathyroidism (PHPT). FNAC complications are rare or mild. We describe the first case in literature of cutaneous spread of parathyroid carcinoma after FNAC.

Pyoderma gangrenosum (PG) is a rare neutrophilic inflammatory skin disease, characterized by recurrent skin ulcers which in almost 50% of cases 1,2 are associated with systemic autoimmune disorders, including rheumatoid arthritis, chronic hepatitis, inflammatory bowel disease, paraproteinemias and hematological malignancies. First described in 1908 by the French Brocq, only in 1930 it was introduced and called PG by Brunsting and colleagues. The true incidence of PG is not really known as it is based on retrospective studies and case series of individuals with inflammatory bowel disease 4,5 ; however, it is estimated to range between 3 and 10 cases per million people per year. 6 Women are more affected than men, with an average age of onset between 40 and 60 years. 7-10 Pediatrics cases are also described, accounting for 4% of total cases. 6 Mortality in people affected by PG it is 3 times higher than in general population, 8 especially for those with inflammatory bowel disease.

The percutaneous biopsy of native kidneys according to the classical methodology is performed under real time ultrasound guidance with the needle introduction along a trajectory of about 30°, aimed to the lower pole of the kidney. Recently, a variant of the classical technique has been introduced by which a perforated ultrasound probe is used to guide the needle along a perpendicular trajectory to the terminal section of the lower kidney pole where the front and back margins of the cortical kidney tissue join each other without renal sinus interposition so to offer to the needle a 3-4 cm thick cortical tissue front which allows to obtain a cortical tissue sample suitable for histological examination even with a single needle pass, while at the same time limiting the possibility of damaging the smaller kidney calices of the lower group whose lesion causes hematuria. In this paper, we present a large survey (50 patients) to compare to data from the literature obtained by using similar...

Histological detection of axillary lymph node metastases is still the most valuable prognostic parameter for breast cancer, but about 30% of node-negative patients relapse within five years, suggesting that current methods are inadequate for identifying metastatic disease. More sensitive, PCR-based methods for the detection of metastatic cells are now available, enabling the amplification of cancer cell-specific mRNA messages by the RT-PCR assay. An ideal tumour marker, consistently expressed in tumour samples and not at all in normal lymph nodes, remains to be identified. The present study first investigated the expression of seven mRNA markers, CEA, CK19, c-Met, mammaglobin, MUC-1, β1→GalNAc-T and p97, selected on the basis of their previously reported specificity for breast cancer cells. Eighteen lymph nodes were examined from patients without tumours. Only mammaglobin mRNA and CEA mRNA were not expressed in normal nodes. All of the other markers showed a band of expression in 17...

IgG4-Related Disease (IgG4-RD) is a fibroinflammatory condition characterized by a typical histopathological pattern (dense lymphoplasmacytic infiltrate with prevalent IgG4+ plasma cells and storiform fibrosis), which may involve the kidney both directly (IgG4-related kidney disease, IgG4-RKD) or indirectly, as a consequence of post-renal ureteral obstruction due to retroperitoneal fibrosis (IgG4-RD RF). The most frequent presentation of IgG4-RKD is IgG4-related tubulointerstitial nephritis (TIN), but a glomerular disease can be present, in most of the cases a membranous nephropathy. Albeit steroid-responsive, in some cases renal manifestations may lead to progressive and permanent organ damage. In this review we describe four clinical cases representative of typical and less typical renal manifestations of IgG4-RD, emphasizing a potential, subclinical, early involvement of the kidney in the disease.

Amyloid A nephropathy is a possible complication of chronic inflammatory disease. Proteinuria and kidney failure are the main features of the disease. Tocilizumab (TCZ), an IL6-R antibody approved for rheumatoid arthritis, is a promising choice for histologically demonstrated nephropathy. We describe a case of kidney amyloid associated with Sweet syndrome treated with TCZ. The patient was affected by Sweet syndrome associated with proteinuria. Kidney biopsy showed amyloid deposits. During the follow-up, cutaneous and renal findings were refractory to many immunosuppressive regimen (cyclophosphamide, leflunomide, interferon and steroid). After few years, the patient developed rapidly progressive nephropathy associated with nephrotic syndrome (proteinuria up to 6 g/die). A second kidney biopsy was performed and it showed worsening of amyloid nephropathy. Thus, TCZ was administrated (8 mg/kg once a month) and it stabilized kidney function and induced partial remission of the nephrotic syndrome in the following 2 years.

Summary. Primary cutaneous follicle center lymphoma (PCFCL) is a rare low-grade cutaneous B-cell lymphoma. Clinically, PCFCL is usually an erythematous subcutaneous nodule or an infiltrated plaque. The dermoscopy is non-specific and it is characterized by polymorphous vascular pattern, arborizing vessels over a salmon-colored background and white areas. We reported a case of a 36-year-old woman presented with a rapidly growing, flashed-color, exophytic, soft consistency nodule on her scalp. Dermoscopy showed a diffuse structureless, skin-color area associated with a rare arborizing vascular pattern and brown circles. We reported a peculiar clinical and dermoscopic variant. This clinical presentation of PCFCL is unusual and represents a pitfall in the early clinical diagnosis. Histopathology is mandatory for a correct diagnosis.

Background: Mitochondrial tRNA (MTT) genes are hotspot for mitochondrial DNA mutation and are responsible of half mitochondrial disease. MTT mutations are associated with a broad spectrum of phenotype often with complex multisystem involvement and complex genotype-phenotype correlations. MT-TL1 mutations, among which the m.3243A>G mutation is the most frequent, are associated with myopathy, maternal inherited diabetes and deafness, MELAS, cardiomyopathy, and focal segmental glomerulosclerosis. Case study: Here we report the case of an Italian 49-years old female presenting with encephalomyopathy, chronic proteinuric kidney disease and a new heteroplasmic m.3274_3275delAC MT-TL1 gene mutation. Conclusions: Our case demonstrates a systemic mitochondrial disease caused by the heteroplasmic m.3274_3275delAC MT-TL1 gene mutation, not yet described in the literature. A mitochondrial disease should be suspected in case of complex multisystem phenotypes, including steroid-resistant nephr...