Kazuo Hara

Clinicopathologic study of nasal T/NK‐cell lymphoma among the Japanese

A high prevalence of nasal lymphoma expressing a T‐ or natural killer (NK)‐cell phenotype (NTCL) with frequent association of Epsteln‐Barr virus (EBV) has been indicated in Asians. To Characterize NTCL among the Japanese, the clinlcopathdogic features of 32 cases were evaluated and the casses worn also analyzed for EBV‐RNA using an ISH method. Morphologically, 31 cases were Identified by atypical pleomorphic lymphoid infiltrates with polymorphous, anglcentric, and necrotic features. Their lymphoma cells ranged in size from small to large and were mixed in varying proportion from case to case. The other one case showed a monomorphic ‘blastic’ appearance. EBV‐encoded small RNA (EBER) was detected in the neoplastic cells of 27 of the 32 cases examined. In the five EBV‐negative cases, one was the ‘blastic’ type. Clonal T‐cell receptor gene rearrangement was detected in none of seven cases examined. The patients had a median follow‐up of 9 months (range, 1 month to 14 years and 11 months). The Kaplan‐Meler estimate of overall survival was 49% at 5 years, correlating with clinical stage. These data support the concept that most cases of NTCL are identified as tumors with T/NK‐cell characteristics and EBV association, distincity different from other peripheral T‐cell lymphomas. Furthermore, the one case of an EBV‐negative ‘blastic’ variant appears not to fit well Into the pleomorphic category but more closely resembles the pathologic features of extranasal angiocentric lymphoma with lymphoblastold appearance. This study also showed no clear difference in clinical aspects other than the original site or in prognosis, between NTCL and extranasal angiocentric lymphomas despite the higher incidence of EBV association and the tendency for that peculiar anatomical site to be restricted to the former group.

Aberrant nuclear/cytoplasmic localization and gene mutation of beta-catenin in classic pulmonary blastoma: beta-catenin immunostaining is useful for distinguishing between classic pulmonary blastoma and a blastomatoid variant of carcinosarcoma.

It is now known that gene mutation of β-catenin with subsequent nuclear/cytoplasmic (N/C) overaccumulation of the protein plays an important role in tumorigenesis of various organs. We recently demonstrated that low-grade adenocarcinoma of the fetal lung type (L-FLAC)/well-differentiated fetal adenocarcinoma (WDFA), the epithelial prototype of classic pulmonary blastoma (CPB), shows N/C localization of β-catenin with genetic mutation. This prompted us to further investigate the state of β-catenin abnormality in CPB and related neoplasms. We studied 9 lung tumors previously diagnosed as biphasic pulmonary blastoma (PB). Histologically, 4 cases (median age 34 years) were CPB with l-FLAC/WDFA as the epithelial component, whereas 5 cases (median age 65 years) were a variant of carcinosarcoma with high-grade FLAC/clear cell adenocarcinoma with fetal lung features as the epithelial component, which we term the blastomatoid variant of carcinosarcoma (BCS). Immunohistochemically, all 4 CPBs showed aberrant N/C localization of β-catenin both in the epithelial and mesenchymal components, with especially high staining intensity in the budding glands and morules. In contrast, all 5 BCSs showed preserved or diminished membranous expression and no significant N/C expression of β-catenin in the epithelial component, and absent or focal N/C expression of β-catenin in the mesenchymal component. Mutational analysis of exon 3 of the β-catenin gene revealed that 3 CPBs harbored missense mutations (S29F, S37F, and S37F), whereas none of the 5 BCSs had this mutation. This study suggests that β-catenin gene mutations may play a role in the tumorigenesis of CPB. Although CPB and BCS have often been grouped together as biphasic PB, they are different entities based on immunohistochemical and molecular analysis of β-catenin. Immunostaining for β-catenin is useful for the discrimination.

Imatinib mesylate inhibits the growth of metastatic lung lesions in a patient with dermatofibrosarcoma protuberans

derived from the neural crest, whereas Langerhans cells are derived from bone marrow. Merkel cells are considered to originate from the neural crest and to form specialized nerve endings. Thus, it is of interest that the p63-negative cells did not originate from epidermal germinative cells. In contrast, skin appendages are derived from epidermal germinative cells in the embryonic stage. The observation that p63 expression was limited to myoepithelial cells both in the eccrine and apocrine glands supports the hypothesis that myoepithelial cells of the sweat glands originate not from mesenchymal cells but from primary epithelial germinative cells. The fact that p63 expression was limited to the outer root sheath cells and hair matrix cells suggests that cells of the inner root sheath would be more differentiated than those of the outer root sheath and hair matrix. Similarly, in terms of p63 expression, vacuolated cells in sebaceous glands and secretory cells of sweat glands are definitively more differentiated than germinative cells. Our results support the concept that p63 is critical for maintaining the germinative cells necessary to sustain epithelial development and morphogenesis. From this exploration of the localization of p63 protein in normal human skin, we postulate that p63 protein may be essential for regulating the differentiation of cells in normal human skin.

Interdigitating cell sarcoma. A morphologic, immunohistologic, and enzyme-histochemical study.

A 58‐year‐old man presented with an unusual sarcoma of the cervical lymph node. The tumor also involved the mesenteric lymph node and jejunum. Tumor cells possessed intracytoplasmic S100 protein, Leu‐3a (T4), and HLA‐DR antigens. The neoplastic cells also showed membranous ATPase activity. LeuM1, T6, Leu1, Leu2a, B1, lysozyme, and immunoglobulin were not recognized. Their fine structure was similar to that of interdigitating cells. These data are consistent with derivation from lymph node interdigitating reticulum cell.

Lichen planus pemphigoides: Identification of 180 kd hemidesmosome antigen

We describe a man with lichen planus pemphigoides. Direct immunofluorescence studies of peribullous skin showed linear deposition of IgG and C3 in the basement membrane zone. Indirect immunofluorescence studies disclosed circulating anti-basement membrane zone antibodies. Immunoelectron microscopy demonstrated binding of antibodies to the hemidesmosomes and lamina lucida. The patients serum defined only the minor bullous pemphigoid antigen with a molecular weight of 180 kd. These findings suggest the coexistence of lichen planus and bullous pemphigoid in lichen planus pemphigoides.

Nodal T/NK‐cell lymphoma of nasal type: a clinicopathological study of six cases

Aims:  To investigate the clinicopathological features of six unusual cases of nodal CD56+ and Epstein–Barr virus (EBV)+ T/natural killer (NK)‐cell lymphoma, a putative nodal counterpart of nasal NK/T‐cell lymphoma (nodal T/NK‐cell lymphoma of nasal type) in comparison with nasal NK/T‐cell lymphoma with secondary lymph node involvement (n = 24) and peripheral T‐cell lymphoma (PTCL) of cytotoxic molecule (CTM)+ and EBV+ type (n = 21).

Nestin expression as a new marker in malignant peripheral nerve sheath tumors.

Malignant peripheral nerve sheath tumor (MPNST) can be difficult to diagnose because it lacks specific immunohistochemical markers. S‐100, which is a useful marker of MPNST, has limited diagnostic utility. Recent studies suggest that nestin, which is an intermediate filament protein, is expressed in neuroectodermal stem cells. The diagnostic utility of immunostains for nestin and three other neural markers (S‐100, CD56 and protein gene product 9.5 (PGP 9.5)) were evaluated in 35 cases of MPNST and in other spindle cell tumors. All MPNST cases were strongly positive for nestin and had cytoplasmic staining. Stains for S‐100, CD56, and PGP 9.5 were positive in fewer cases (17/35, 11/35, and 29/35 cases, respectively), and had less extensive staining. Nestin was negative in 10/10 leiomyomas, and weak nestin expression was seen in 10/10 schwannomas, 3/10 neurofibromas, 2/8 synovial sarcomas, 2/10 liposarcomas, 4/7 carcinosarcomas and 3/7 malignant fibrous histiocytomas. In contrast, strong nestin positivity was seen in 10/10 rhabdomyosarcomas, 15/19 leiomyosarcomas, and 9/9 desmoplastic melanomas. Nestin is more sensitive for MPNST than other neural markers and immunostains for nestin in combination with other markers could be useful in the diagnosis of MPNST.

Anomaly of the inferior vena cava observed by CT

Computed tomography (CT) is a good modality for diagnosing diseases of the retroperitoneal space and capable of showing the abnormality of inferior vena cava (IVC) without using invasive technique. To determine the incidence of the anomaly of IVC, the computed tomograms were investigated retrospectively. The incidence were 0.69% in left side IVC, 1.03% in double IVC and 0.08% in azygos continuation.

Clinicopathological analysis of the age-related differences in patients with Epstein–Barr virus (EBV)-associated extranasal natural killer (NK)/T-cell lymphoma with reference to the relationship with aggressive NK cell leukaemia and chronic active EBV infection-associated lymphoproliferative disorders

Takahashi E, Ohshima K, Kimura H, Hara K, Suzuki R, Kawa K, Eimoto T & Nakamura S for the NK‐cell Tumor Study Group 
(2011) Histopathology59, 660–671

Melanocytic lesions in lymph nodes associated with congenital naevus

Two cases of melanocytic lesions in lymph node associated with congenital naevus are presented. The first was a 30‐year‐old man with a nodular melanoma arising in a small congenital naevus. The second was a 2‐year‐old male infant with a giant congenital naevus. In both cases, naevus cell aggregates were observed in the capsule, trabeculae, perisinusoidal areas and lymphatic vessels surrounding the nodes. In the first case, clusters of large atypical melanocytes were present amongst naevus cell aggregates in the perisinusoidal areas as well as in the lymphoid parenchyma. Between the naevus cells and large atypical melanocytes, transitional forms were observed which supports the idea that the presence of large atypical melanocytes is indicative of benign naevus cells. In the second case, marginal sinuses were packed with clusters of large melanin‐rich cells. Immunohistochemically, these cells were S‐100 protein negative, but ultrastructural studies proved them to be melanocytes. They were considered indicative of spread of benign naevus cells via lymphatic vessels. Arrested migration of naevus cells during embryogenesis and benign spread of naevus cells are possible explanations for the histogenesis of naevus cell aggregates in lymph nodes associated with congenital naevus.