Giacomo Fiandrino

Twenty-one cases of blastic plasmacytoid dendritic cell neoplasm: focus on biallelic locus 9p21.3 deletion

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive malignancy derived from precursors of plasmacytoid dendritic cells. We analyzed 21 cases with array-based comparative genomic hybridization (aCGH). Complete or partial chromosomal losses largely outnumbered the gains, with common deleted regions involving 9p21.3 (CDKN2A/CDKN2B), 13q13.1-q14.3 (RB1), 12p13.2-p13.1 (CDKN1B), 13q11-q12 (LATS2), and 7p12.2 (IKZF1) regions. CDKN2A/CDKN2B deletion was confirmed by FISH. This scenario argues for disruption of cell cycle at G(1)/S transition, representing a genetic landmark of BPDCN, and possibly contributing to its pathogenesis. Statistical analysis of overall survival in our series highlighted an association of poor outcome with biallelic loss of locus 9p21.3. We suggest that, in the absence of reliable parameters for predicting prognosis in BPDCN other than age, tumor stage, and/or clinical presentation, simple methods, such as FISH for CDKN2A/CDKN2B, could help to identify the most aggressive cases.

Spleen endothelial cells from patients with myelofibrosis harbor the JAK2V617F mutation.

Increased microvessel density contributes to abnormal BM and spleen microenvironment in myelofibrosis (MF). Taking advantage of the JAK2V617F mutation as a marker of malignancy, in the present study, we investigated whether splenic endothelial cells (ECs) obtained from capillaries by laser microdissection or from fresh spleen tissue by cell culture or cell sorting harbored such mutation in patients bearing the mutation in their granulocytes and undergoing splenectomy for therapeutical reasons. To extend the analysis to the ECs of large vessels, endothelial tissue from the splenic vein was also studied. We found JAK2V617F(+) ECs in 12 of 18 patients also bearing the mutation in their granulocytes. In 3 patients, the mutation was found in at least 2 different EC samples obtained by laser microdissection, cell culture, or cell sorting. The mutation was detected in the splenic vein ECs of 1 of 6 patients investigated. In conclusion, we provide evidence that some ECs from the spleen and splenic veins of patients with MF bear the JAK2V617F mutation. We suggest that splenic ECs are involved in the process of malignant transformation in MF.

Mandibular traumatic peripheral osteoma: a case report.

An osteoma is a slow-growing, benign lesion comprising mature bone tissue. Osteomas rarely occur in maxillary bones, with the exception of the maxillary sinuses. Various possible etiologies have been proposed, including congenital anomalies, chronic inflammation, muscular activity, embryogenetic changes, and trauma. Here we present a case of an osteoma of the buccal plate of the mandible at the site where a sports-related traumatic injury occurred 15 years earlier. Both conventional and 3-dimensional x-ray examinations were used for diagnosis and preoperative evaluation of the possible involvement of the adjacent anatomic structures. The lesion was treated surgically without complications and the patient made a complete recovery. Histologic tests confirmed the preoperative diagnosis. A review of the international literature is also presented.

CD5− diffuse large B-cell lymphoma with peculiar cyclin D1+ phenotype. Pathologic and molecular characterization of a single case

Increased expression of cyclin D1 is notoriously associated with mantle cell lymphoma because of translocation t(11;14)(q13;q32) or variants involving the cyclin D1 gene. We present an unusual case of CD5-negative diffuse large B-cell lymphoma expressing cyclin D1 in the absence of translocation by fluorescence in situ hybridization analysis. Using array-comparative genomic hybridization, we found a complex karyotype without the characteristic chromosomal aberrations accompanying cyclin D1 translocation in mantle cell lymphoma; instead, there was monoallelic deletion of AKT interacting protein and glycogen synthase kinase-3 β genes, both involved in the AKT/glycogen synthase kinase-3 β cascade-controlling nuclear levels of cyclin D1. These findings suggest that posttranslational events regulating cyclin D1 activity may take place also in a subset of diffuse large B-cell lymphomas and contribute to lymphomagenesis. As a consequence, the sole cyclin D1 positivity by immunohistochemistry may not be enough to distinguish pleomorphic/blastoid mantle cell lymphoma from diffuse large B-cell lymphoma. Search for t(11;14) with fluorescence in situ hybridization probes should always be performed in doubtful cases.

Photoinduced dermatitis and oral lichenoid reaction in a chronic myeloid leukemia patient treated with imatinib mesylate

Imatinib mesylate (IM) is a phenylaminopyrimidine that represents the first‐line treatment for chronic myeloid leukemia (CML), Philadelphia chromosome‐positive. It acts as a potent and selective inhibitor of the bcr‐abl fusion protein by a competitive inhibition at the adenosine triphosphate‐binding site of the enzyme, which leads to the inhibition of tyrosine phosphorylation of the proteins involved in bcr‐abl signal transduction. IM is generally well tolerated and usually provokes only mild side effects consisting of nausea, myalgia, edema and muscle cramps.

Congenital aggressive variant of Langerhans cells histiocytosis with CD56+/E‐Cadherin− phenotype

In children <2 years of age, cutaneous involvement is the most frequent presentation of Langerhans cell histiocytosis (LCH). Cutaneous LCH can be localized or associated with dissemination and organ dysfunction. The clinical course is variable, ranging from spontaneous regression to a fatal outcome. We describe a female newborn presenting with congenital cutaneous lesions who rapidly developed pulmonary infiltrates and multiple osteolytic lesions. Skin biopsy showed a dermal infiltrate of medium to large cells morphologically and phenotypically consistent with LCH. The clinical course was rapidly fatal in spite of chemotherapy. No strict correlation between morphology and prognosis has been documented in LCH, but, in our case, distinct morphological and immunohistochemical features (CD56 expression and no E‐Cadherin expression) may have contributed to an aggressive clinical course. Pediatr Blood Cancer 2009;53:1107–1110.

A Metachronous splenic metastases from esophageal cancer: a case report

The spleen is an infrequent site for metastatic lesions, and solitary splenic metastases from squamous cell carcinoma of the esophagus are very rare: only 4 cases have been reported thus far. These lesions are whitish nodules that are macroscopically and radiologically similar to primary splenic lymphomas. We report a case of metachronous splenic metastases from esophageal cancer and multiple splenic abscesses, which developed nine months after apparently curative esophagectomy without adjuvant chemotherapy. The patient underwent splenectomy dissection followed by adjuvant chemotherapy, but liver and skin metastases developed, and the patient died 9 months later.

Unique vascular tumor primary arising in the liver and exhibiting histopathological features consistent with so‐called polymorphous hemangioendothelioma

Reported herein is an unusual vascular tumor primary arising in the liver and exhibiting unique histopathological features. A 47‐year‐old woman underwent left hepatectomy because of a large hepatic mass. On histology the tumor had a composite pattern, consisting of angiomatous, retiform and solid areas, formed by oval to cuboidal to spindle cells, that expressed only endothelial markers (CD31 and factor VIII‐related antigen). These findings led to the diagnosis of a low‐grade vascular neoplasm with morphological features consistent with so‐called polymorphous hemangioendothelioma. The tumor was completely resected. At 24 month follow up the patient was alive, without evidence of disease. Polymorphous hemangioendothelioma is a rare vascular neoplasm, with borderline malignant potential, which usually occurs in lymph nodes and, rarely, at extranodal sites. Its classification as an entity has been questioned recently. The unusual morphological features of the present case, which do not fit neatly with any other recognized hemangioendothelioma subtype, indicate that the family of vascular tumors is broader than currently accepted. In addition the present case widens the spectrum of primary vascular tumors arising in the liver.

Sporotrichoid metastases to the skin from cutaneous squamous cell carcinoma in an immunocompetent patient.

Squamous cell carcinoma (SCC) of the skin may metastasize in more than 5% of cases. Metastases usually involve the primary regional lymph nodes in 85% of cases. The skin is rarely involved by metastases of SCC of the skin. The presence of multiple cutaneous metastases in a figurate array is a very rare occurrence, mostly reported in SCC occurring in immunocompromized patients. The case of a 70-year-old immunocompetent patient, with an ulcerated primary SCC on his right palm and 3 nodules in a linear array on his right arm is described. He also presented with homolateral axillary lymphadenopathy. Histopathologic examination from the 3 nodules revealed SCC of variable grading, with focal fusion of the metastases with the overlying epidermis. The patient had been previously treated with chemotherapy and radiotherapy in another Department, with no benefit. Despite right arm amputation and homolateral axillary lymphadenectomy, the patient died 4 months after a procedure, for pulmonary embolism.

Absence of MYD88 L265P mutation in blastic plasmacytoid dendritic cell neoplasm.

high amount of IL-22 (Fig. 2d). We treated the patient with systemic antibiotics (vancomycin and linezolid) because of sepsis due to methicillin-resistant Staphylococcus aureus (MRSA). The antibiotics improved pyogenic spondylitis causative for sepsis, but did not change the frequency of circulating or skin-infiltrating CD8 tumour cells. Concomitantly with the infection improvement, 5 weeks later, the serum IL-22 level was dramatically decreased (Fig. 2e). Both aggressive and indolent subtypes of CD8 CTCL exist. While the indolent type includes CD8 variants of mycosis fungoides, Sézary syndrome and anaplastic large-cell lymphoma, the aggressive type is represented by primary cutaneous CD8 epidermotropic cytotoxic T-cell lymphoma. In our case, circulating CD8 tumour cells were positive for CD7 (CD8CD7; 47Æ7%), but negative for CD2 (CD8CD2; 38Æ2%), which shares the phenotype with the aggressive type of CD8 CTCL. However, we diagnosed the eruption as CD8 variant of Sézary syndrome because of its clinically indolent course or histologically TIA-1-negative property. The enhanced IL-22 production can be seen in the immunoactivation associated with bacterial infection. Recently, increased serum IL-22 levels were reported in patients with CTCL, suggesting the correlation with bacterial infections in affected skin. The mean serum levels of IL-22 in patients with abdominal septic shock was 111Æ8 pg mL. Our patient showed a higher serum level of IL-22 than those patients, suggesting that CD8 tumour cells produced the high amount of IL-22 possibly responding to bacterial pathogens. We speculate that the malignant CD8 T cells responded to bacterial pathogens and had a capacity to produce IL-22, which contributed to host immune defence.