Emiko Takahashi

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.

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

Nodal cytotoxic molecule (CM)-positive Epstein-Barr virus (EBV)-associated peripheral T cell lymphoma (PTCL): a clinicopathological study of 26 cases.

Kato S, Takahashi E, Asano N, Tanaka T, Megahed N, Kinoshita T & Nakamura S 
(2012) Histopathology 61, 186–199

Primary cutaneous T‐cell lymphoma of unspecified type with cytotoxic phenotype: Clinicopathological analysis of 27 patients

The objective of our study was to investigate the clinicopathological features of the currently ill‐defined subtype of primary cutaneous T‐cell lymphoma of unspecified type (CTCLU) with a cytotoxic phenotype and no Epstein–Barr virus (EBV) association. A series of 27 patients with CTCLU (median age 49 years; range 25–87 years; 18 men) was reviewed. Performance status scores above 1 (7%), clinical stages above 2 (15%), B symptoms (26%), extracutaneous involvement (30%), and a fatal course within 1 year of diagnosis (19%) were observed infrequently. The International Prognostic Index was high or high to intermediate in 11%, and the Prognostic Index for Peripheral T‐cell Lymphoma unspecified was above group 2 in 22%. Notably, the rates of spontaneous regression and T‐cell receptor gene rearrangements by polymerase chain reaction analysis were seen in 26 and 17% of our cases, respectively. Histologically, 22 patients had subcutaneous involvement of whom eight showed a lethal clinical course, and five patients without subcutaneous involvement were all survivors. Immunophenotypical and morphological features allowed us to subclassify our cases according to the following four categories: (1) epidermotropic CD8+ T‐cell lymphoma (n = 5); (2) cutaneous γ/δ T‐cell lymphoma (n = 8); (3) cutaneous α/β pleomorphic T‐cell lymphoma (n = 8); and (4) cutaneous medium/large pleomorphic T‐cell lymphoma, not otherwise specified (n = 6). All four of these groups of lymphomas exhibited a relatively favorable clinical course compared to previous reports. However, epidermotropic CD8+ T‐cell lymphoma appeared to be unique with a higher ratio (80%) of spontaneous regression, a lower ratio (40%) of subcutaneous involvement, and a more favorable clinical course than the other three subcategories. (Cancer Sci 2009; 100: 33–41)

Primary IgG4-related lymphadenopathy with prominent granulomatous inflammation and reactivation of Epstein–Barr virus

We report a unique case of primary IgG4-related lymphadenopathy showing prominent granulomatous inflammation and Epstein–Barr virus (EBV) reactivation. Involved lymph nodes showed an expanded interfollicular zone with prominent granulomatous inflammation, including a predominance of epithelioid macrophages and occasional Langhans multinucleated giant cells. Bundles of spindle cells were also observed. Intermingled with the granulomatous inflammation were numerous mature plasma cells, eosinophils, and neutrophils. The percentage of IgG4+/IgG+ plasma cells was markedly elevated (70%), along with raised serum IgG4 levels. The plasma cells did not show immunoglobulin light-chain restriction. EBV-positive lymphocytes were scattered throughout the paracortical areas. Corticosteroid treatment was very effective. IgG4-related lymphadenopathy has a broad histological spectrum and might be misdiagnosed due to other conditions which morphologically closely resemble it. The correct diagnosis is important in view of the remarkable response to steroid therapy.

A Case of Estrogen Receptor Positive Secretory Carcinoma in a 9-Year-old Girl With ETV6–NTRK3 Fusion Gene

The patient was a 9-year-old premenarcheal pediatric female, whose chief complaint was a well-circumscribed palpable right breast mass without nipple discharge. Although the patient had noticed the lump 2 years prior to hospital admission, its size (1.5 × 1.3 cm) had been stable. There was no family history or previous history of malignancies. Physical examination showed a well-delimited, elastic-firm and movable tumor just beneath the nipple and areolar complex. Regional lymph nodes were not palpable. Ultrasonography and breast computed tomography revealed a subareolar oval-shaped tumor exhibiting homogeneous echogenicity with clear margins. Distant metastases could not be detected using whole-body computed tomographic scans. A fine-needle aspiration cytology specimen showed atypical cells with prominent nucleoli and abundant intracellular secretory material, suggesting the possibility of secretory carcinoma. Histopathological analysis of the core needle biopsy specimen revealed that the tumor was a secretory carcinoma. The patient underwent total mastectomy with sentinel lymph node biopsy. Metastases were not observed in the removed lymph nodes. Estrogen receptor was weakly positive and progesterone receptor was negative. Human epidermal growth factor receptor 2 expression was also negative. In addition, the ETV6 (exon 5) and NTRK3 (exon 13) fusion gene was detected using the reverse transcription-polymerase chain reaction method. This gene is considered specific for secretory carcinoma. Immunohistochemistry revealed weak basal differentiation [cytokeratin 5/6(CK5/6)(+), vimentin(+) and epidermal growth factor receptor(+)]. The patient has received no adjuvant therapy and is currently disease free at 12 months after surgery.

Case of malignant transformation of vagus nerve schwannoma to angiosarcoma

It is known that benign tumors have the potential for malignant transformation. Malignant transformation of vagus nerve schwannoma to angiosarcoma is very rare.

Epstein-Barr virus–positive cytotoxic T-cell lymphoma followed by chronic active Epstein-Barr virus infection–associated T/NK-cell lymphoproliferative disorder: a case report

A 30-year-old female patient presented with intestinal Epstein-Barr virus (EBV)-positive cytotoxic T-cell lymphoma (EBV+ CTL), which was surgically resected. Fourteen years later, she returned to our hospital with hypersensitivity to mosquito bites and was diagnosed with chronic active EBV infection-associated T/NK-cell lymphoproliferative disorder (CAEBV/TNK-LPD). She developed systemic EBV+ CTL at age 47 years during the 2.5-year clinical course of CAEBV/TNK-LPD, despite multiagent chemotherapy and allogeneic stem cell transplantation. Afterward, she had a rapidly deteriorating clinical course and died at age 48 years. The immunophenotype of the EBV+ CTL was consistently a CD3, CD8, and cytotoxic molecule-positive type with the same clonality in polymerase chain reaction analysis of T-cell receptor-γ chain gene rearrangement. This is the first reported case of EBV+ CTL preceding the clinical presentation of CAEBV/TNK-LPD. The present case was unique in suggesting a close relationship between EBV+ CTL and chronic active EBV infection.

Clinicopathological analysis of 12 patients with Epstein-Barr virus-positive primary intestinal T/natural killer-cell lymphoma (EBV+ ITNKL)

Epstein–Barr virus‐positive (EBV+) intestinal T/natural killer (NK) cell lymphoma (ITNKL) is an uncommon tumour with an extremely aggressive clinical behaviour. However, the clinicopathological characteristics of this tumour, including T cell receptor (TCR) phenotype and the patients background, remain unknown. The aim of this study was to elucidate the detailed clinicopathological profile of EBV+ ITNKL.