Hiroyuki Hanakawa

Clinicopathologic analysis of IgG4-related skin disease

IgG4-related disease is a recently recognized systemic syndrome characterized by mass-forming lesions with lymphoplasmacytic infiltration, increase in the number of IgG4+ cells in affected tissues and elevation of serum IgG4 levels. In 2009, we were the first to report skin lesions in patients with IgG4-related disease, but no large case series has been reported and clinicopathological findings remain unclear. To clarify these features, we herein report 10 patients (9 men and 1 woman; median age, 64 years; age range, 46–81 years) with IgG4-related skin disease. All patients had erythematous and itchy plaques or subcutaneous nodules on the skin of the head and neck, particularly in the periauricular, cheek, and mandible regions, except for one patient, whose forearm and waist skin were affected. In addition, eight patients had extracutaneous lesions: these were found on the lymph nodes in six patients, the lacrimal glands in three patients, the parotid glands in three patients, and the kidney in one patient. Histologically examined extracutaneous lesions were consistent with IgG4-related disease; five of six lymph node lesions showed progressively transformed germinal centers-type IgG4-related lymphadenopathy. Cases of IgG4-related skin disease were classified into two histological patterns: those exhibiting a nodular dermatitis pattern and those with a subcutaneous nodule pattern. The infiltrate was rich in plasma cells, small lymphocytes, and eosinophils; the majority of the plasma cells were IgG4+. The IgG4+ cell count was 49–396 per high-power field (mean±s.d., 172±129), with an IgG4+/IgG+ cell ratio ranging from 62 to 92%. Serum IgG4 levels were elevated in all examined patients. In conclusion, patients with IgG4-related skin disease had uniform clinicopathology. Lesions were frequently present on the skin of the periauricular, cheek, and mandible regions, and were frequently accompanied by IgG4-related lymphadenopathy.

Regulatory T-cell infiltration in tongue squamous cell carcinoma

Abstract Conclusion: In tongue squamous cell carcinoma (SCC), high levels of regulatory T-cell (Treg) infiltration in tumor nests are observed in the cases with poor prognosis. Objectives: The role of Tregs in head and neck cancers remains unclear. The aim of this study was to observe the distribution of Tregs in different stages of tongue SCC and estimate the effects on prognosis. Methods: Thirty-four cases with tongue SCC were examined immunohistochemically for CD4, CD8, and Forkhead box P3 (Foxp3). Immunoreactive cells were counted in cancer stroma and nest regions, and relationships between cell numbers and disease-free survival rates were analyzed. Results: In the 34 cases, univariate analysis for disease-free survival indicated high-level infiltration of Tregs (CD4+Foxp3+) into both cancer nests and stroma and presence of helper T (CD4+Foxp3–) cells in cancer stroma as potential predictors of significantly worse prognosis. In early-stage cases (stage I/II), high-level infiltration of Tregs in cancer nests correlated significantly with poor disease-free survival rate. Multivariate analysis for disease-free survival found no independent variables.

Minimally Invasive Procedure for Accurate Diagnosis of Mucosa-associated Lymphoid Tissue Lymphoma of the Head and Neck

Sonography-guided cutting needle biopsy for the diagnosis of malignant lymphoma has recently come into wide use. However, surgery is sometimes unavoidable for the diagnosis of malignant lymphoma, particularly for low-grade malignant lymphoma such as extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, because cutting needle biopsy offers limited diagnostic accuracy for low-grade malignant lymphoma. Of course, unnecessary invasive procedures like open biopsy should be avoided wherever possible, given the cosmetic problems and burden on the patient. We tried to diagnose malignant lymphoma using the combination of cutting needle biopsy, flow cytometry and polymerase chain reaction to identify monoclonal rearrangement of immunoglobulin heavy chain genes. We have used this method in two cases in whom malignant lymphoma was suspected in the head and neck region, allowing diagnosis of mucosa-associated lymphoid tissue lymphoma in both cases. One case involved a 23-year-old woman with mucosa-associated lymphoid tissue lymphoma in the parotid glands, and the other involved a 77-year-old man with mucosa-associated lymphoid tissue lymphoma in the thyroid. The combination of cutting needle biopsy, flow cytometry and immunoglobulin heavy chain gene rearrangement testing might offer a useful alternative to open biopsy for the diagnosis of mucosa-associated lymphoid tissue lymphoma. We recommend this procedure, particularly for young women or patients with poor performance status in whom malignant lymphoma is suspected.

Novel and simple prognostic index for nasal natural killer/T‐cell lymphoma

Few studies have investigated the prognostic factors for nasal natural killer (NK)/T‐cell lymphoma.

Characteristic ultrasound features of mucosa-associated lymphoid tissue lymphoma of the salivary and thyroid gland

Abstract Conclusion: The characteristic ultrasound appearance of mucosa-associated lymphoid tissue (MALT) lymphoma of the head and neck provides diagnostic information regarding masses or swellings in the head and neck region. Objectives: There are only a few reports about ultrasound features of malignant lymphoma (ML) of the head and neck. We have noticed that the ultrasound appearances of cases with MALT lymphoma resembled each other even when the appearances of other images like computed tomography were absolutely different. The objective of this study was to delineate the reliability of this characteristic ultrasound appearance of MALT lymphoma of the head and neck. Methods: The ultrasound examinations of 30 patients with histopathologically proven primary ML of the head and neck (15 cases of MALT) were reviewed. The ultrasound results of each case were independently compared to the results of the histopathological examination. Results: Two ultrasound patterns were observed for MALT lymphoma. The first was characterized by a marked hypoechoic area with interspersed linear echogenic strands (linear echogenic strands pattern), and the second was characterized by multiple, relatively large, hypoechoic segments (segmental pattern). Histopathologically, these patterns could be explained on the basis of the expansion of lymphoma cells demarcated by narrow or wide fibrous bands.

Regulatory T cells function at the early stage of tumor progression in a mouse model of tongue squamous cell carcinoma.

The objective of this study was to observe the distribution of regulatory T cells (Tregs) in the development of tongue squamous cell carcinoma (SCC) and to determine the role of Tregs in the progression of tongue SCC. A mouse model of 4-nitroquinoline-1-oxide (4NQO)-induced-tongue SCC was established. The expression of Forkhead box P3 (Foxp3), interleukin 10, transforming growth factor-β, chemokine CC motif ligands 17, 20, and CC chemokine receptor 4 was determined using real-time quantitative polymerase chain reaction. Foxp3 expression was also analyzed using immunohistochemistry. The results were compared with those of control mice and of 4NQO-treated mice treated with a cyclooxygenase-2 (COX-2) inhibitor. Well to moderately differentiated tongue SCC was induced in all of the experimental mice. The amount of Tregs of the experimental mice was over 10 times as much as control mice at the early stage of tumor progression. COX-2 inhibitor did not prevent the progression of tongue SCC and did not reduce the total amount of Tregs. Tregs function at the early stage of the development of tongue SCC, and it may be effective to suppress Tregs at the early stage of tumor progression for the treatment and/or prevention of tongue SCC.

Does HMGB1 predict occult neck lymph node metastasis in early tongue carcinoma? A case-control study of 26 patients

OBJECTIVE This study examined whether the occurrence of late neck metastasis in early tongue squamous cell carcinoma can be predicted by evaluating HMGB1 (high mobility group box 1) expression in the primary lesion. METHODS A case-control study was conducted. The cases comprised 10 patients with late neck metastasis. The controls consisted of 16 patients without recurrence. All were examined immunohistochemically for HMGB1 protein expression. The odds ratio for late neck metastasis in relation to HMGB1 was estimated. RESULTS RESULTS for HMGB1 were dichotomised into positive staining scores (score, 5-7) and negative scores (0-4). Six cases (60 per cent) and four controls (25 per cent) were HMGB1-positive. Although no significant result was seen, compared with HMGB1-negative patients the odds ratio for late neck metastasis in HMGB1-positive patients was 3.8 (95 per cent confidence interval, 0.6-26.5) after adjusting for other factors. CONCLUSION In the present study, immunohistochemical study of HMGB1 in early tongue squamous cell carcinoma did not appear to be very useful for predicting occult neck metastasis. Further study is necessary to clarify the relationship between HMGB1 expression and late neck metastasis in early tongue squamous cell carcinoma.

Cutting needle biopsy combined with immunohistochemical study of myeloperoxidase for the diagnosis of histiocytic necrotizing lymphadenitis

Abstract Conclusion: Cutting needle biopsy (CNB) combined with immunohistochemical study of myeloperoxidase (MPO) is a useful minimally invasive diagnostic procedure for histiocytic necrotizing lymphadenitis (HNL). Objectives: HNL is mainly diagnosed by pathological findings of open surgical biopsy (OSB) specimens. Recently the appearance of anti-MPO positive histiocytes has been reported as a highly specific pathological diagnosis for HNL. Considering the cosmetic impact and burden on the patients, we performed CNB combined with immunohistochemical study of MPO for the diagnosis of HNL. Few studies have reported the utility of this method in the diagnosis of HNL. Methods: A retrospective study was conducted using clinical data from 20 HNL patients. Results: CNB was performed in 8 patients and OSB in 13 (OSB after CNB in 1). MPO-positive histiocytes were observed in all of the 20 cases. The accuracy of the diagnoses was finally confirmed by the clinical courses in all cases.