Kazuyuki Ishihara

Statistical profiles of malignant melanoma and other skin cancers in Japan: 2007 update

BackgroundIn the previous report of the Prognosis and Statistical Investigation Committee of the Japanese Skin Cancer Society, we tabulated data on patients with malignant melanoma who had been registered at major medical institutions (22 institutions on average) in Japan over 5-year periods from 1987 to 1991 (group A) and from 1992 to 1996 (group B). In the present study, patients registered from 1997 to 2001 (group C) were investigated and the data were compared with findings obtained by the subsequent follow-up of groups A and B.MethodsThe numbers of melanoma patients registered were: 545 in group A (1987–1991), 699 in group B (1992–1996), and 821 in group C (1997–2001). Because the International Union Against Cancer (UICC) TNM and stage classifications for malignant melanoma were changed substantially in 2002, analyses in the present investigation were performed according to the new classifications. The Kaplan-Meier method was used to draw survival curves, and the log-rank test was used to assess the significance of differences in survival. In addition, the numbers of patients with various kinds of skin malignancies, including not only malignant melanoma but also basal cell carcinoma, squamous cell carcinoma, mycosis fungoides, actinic keratosis, Bowen’s disease, and Paget’s disease, registered at approximately 100 medical institutions in Japan from 1987 to 2001, were also investigated and data were tabulated.ResultsThe nationwide survey of Japanese patients with malignant skin tumors from 1987 to 2001 showed that the most prevalent skin tumor was basal cell carcinoma, which increased year by year, followed by squamous cell carcinoma, and then by malignant melanoma. The following results were obtained from the data for melanoma patients registered at major institutions from 1987 to 2001. (1) The overall 10-year survival rates for melanoma patients in each chronological group were ranked as: group C > B > A, although only the difference between groups C and A was statistically significant. (2) The male-to-female ratio ranged from 1: 0.97 to 1: 1.14, and the survival rate of female patients was higher than that of male patients (the 140-month survival rate was 70.6% in females and 60% in males). (3) Assessment of the age distribution showed that the number of patients increased rapidly from ages 40–49 years and reached a peak at around 60 years in all three groups. (4) The sole of the foot was the most common site of melanoma in both males and females, while melanomas on the lower limbs were also prevalent in females. (5) Acral lentiginous melanoma (ALM) was the most common type in all three groups, accounting for nearly 50% of the patients in each group. The number of patients with superficial spreading melanoma (SSM) increased steadily over time and exceeded the number of patients with nodular melanoma (NM) in group C. The prognosis of NM was the worst, while that of SSM was the most favorable. (6) The proportion of stage I patients was larger in group C than in groups A and B, but no significant difference among the groups was observed in the proportions of stage II, III, and IV patients. For patients in stage III, the overall survival rate was higher in group C than that in group A or B, while there was no apparent difference in survival between the groups for patients in stage I or II. For patients in stage IV, the survival rate in group C was slightly lower than that in group A or B. (7) In group C, the overall survival rates for substages III A, B, and C were ranked as III A > III B > III C. (8) The overall survival rates for stage IV M1a, M1b, and M1c were ranked as M1a > M1b > M1c. In group C, the overall survival rate of stage IV patients with a normal serum lactic dehydrogenase (LDH) level was higher than that of patients with elevated LDH values. (9) Evaluation of the effects of some therapeutic procedures (prophylactic lymph node dissection and chemotherapy with and without interferon-beta) on the survivals of patients with melanoma was inconclusive and suggested the need for more studies in this area.ConclusionIn Japan, the number of patients with malignant skin tumors has increased year by year. The prognosis of patients with advanced malignant melanoma remains extremely poor, but that of patients in stage III has shown an improvement.

Updated statistical data for malignant melanoma in Japan.

AbstractBackground. A statistical investigation was conducted of Japanese melanoma patients who had been registered by the Prognosis and Statistical Investigation Committee of the Japanese Skin Cancer Society. The data were obtained from 24 main medical institutions in Japan in the period 1987 to 1996. The patients were classified into two chronological groups; group A, 535 patients registered from 1987 to 1991; and group B, 639 patients registered from 1992 to 1996. As the preliminary data for group A has been reported previously (Gann Monograph on Cancer Research 43), in this report, the survival data of group B were assessed, and compared with the data for group A. Methods. The data analyzed included age, sex, anatomical distribution, clinical features of primary lesions, Clarks subtype, tumor thickness, Clarks level, disease stage, and treatment. The survival rate was assessed by the Kaplan-Meier method, and the significance of differences was determined with the log-rank test. In addition, the results of a nationwide survey of various types of skin malignancies, obtained from 101 medical institutions in Japan between 1987 and 1996, were analyzed. Results. The nationwide survey revealed that the number of patients with malignant melanoma showed a steady increase during the period 1987–1996 in Japan. It is noteworthy that the numbers of actinic keratoses, a type of early squamous cell carcinoma in situ, showed a steep increase in recent years. Results revealed in our study of the melanoma registry for the period 1987–1996 were as follows: (1) the male-to-female ratio was 1 to 1.06, (2) the survival rate of female patients was higher than that of male patients (10-year survival in group B: female, 71.6% vs male, 55.9%), (3) the commonest site of melanoma in both sexes was the sole of the foot, (4) with respect to Clarks subtype, acral lentiginous melanoma was commonest, accounting for about half of all melanomas, (5) nodular melanoma showed the worst prognosis among the subtypes, (6) patients in stage IIIB and stage IV had an unfavorable outcome, with 10-year survivals of less than 50% and less than 10%, respectively, (7) Clarks level of invasion, as well as Breslows tumor thickness of the primary lesions, were confirmed to be important prognostic factors, and (8) prophylactic lymph node dissection in stage II and IIIA and chemotherapy in stage IV seemed to have limited effect on the prognosis. Conclusion. The prognosis of advanced melanoma is poor, as it is highly resistant to chemotherapy. Thus, to improve the prognosis, early detection is mandatory, and this is possible because this neoplasm appears as a distinctive pigmented lesion on the skin.

Sebaceous Gland and Sweat Gland Carcinomas of the Skin Clinicopathological Study and Significance of c‐erbB‐2 Oncoprotein Expression

Thirteen sebaceous gland carcinomas and 10 sweat gland carcinomas were examined to elucidate any important histological parameters influencing their prognosis, and the relationship between immunohistochemical expressions of c‐erbB‐2 oncoprotein and survival of the patients was analyzed. Sebaceous gland carcinomas with vacuolated cytoplasm in more than 50% of whole tumor area, with necrosis, and without lymphoid cell infiltration in tumor nests and stroma had a higher incidence of tumor recurrence and tumor‐related death than tumors with vacuolated cytoplasm in 50% or less of whole tumor area (p < 0.01), without necrosis, and with lymphoid cell infiltration in tumor nest and stroma (p < 0.05). Sweat gland carcinomas of all cases with fatal outcomes demonstrated tubular differentiation in 20% or less of whole tumor area, lymphatic permeation and desmoplastic reaction. Three sebaceous gland carcinomas and three sweat gland carcinomas were positive for c‐erbB‐2 oncoprotein. Two of three sebaceous gland carcinomas, and all three sweat gland carcinomas developed tumor recurrence and ended in tumor‐related deaths. Sweat gland carcinomas with c erbB 2 expression had significantly shorter survival than those with negative immunostain (p < 0.01). Cytoplasmic appearance, tumor necrosis, and lymphoid cell infiltration in tumor nests and stroma of sebaceous gland carcinoma, and tubular differentiation, lymphatic permeation, and growth patterns of sweat gland carcinoma are considered to closely correlate to the prognosis. Immunohisto‐chemically detected c erbB 2 oncoprotein may be an indicator of bad prognosis. Acta Pathol Jpn 42: 585–594, 1992.

An effective case of IFN-.BETA. for multiple skin metastases of melanoma.

メラノーマの多発皮膚転移の2症例についてIFN-β (フエロン) の腫瘍内投与を試みた。1例はstageIIIで来院し, 原発巣の潰瘍化および所属リンパ節の転移の見られた症例で, 準治療後1年目に皮膚および皮下に多発転移が発生したものである。他臓器に転移の見られないことよりIFN-β単独で長期の腫瘍内投与によりすべての転移巣 (101個) を消失せしめ10年以上再発,転移を認めなかった。かかる症例は稀有といわざるを得ない。2例目は他施設で試験切除を施行し, 若干の期間を経て原発巣の広範切除と所属リンパ節郭清し, 10ヵ月後に同側下肢と所属リンパ節を越えた皮膚転移の多発を見た症例である。化学療法は無効であった。IFN-βの投与によりすべてを消失せしめ得た。副作用に関してはいずれの症例も問題となるものはなかった。

Observation of antitumor effect of BCG live bacteria for nue mouse transplantabile human malignant melanoma.

ヌードマウス可移植性ヒト悪性黒色腫 (SK-14) に対してBCG生菌の抗腫瘍効果を検討した。移植腫瘍の成長を確認後, コントロール群 (生理的食塩水) , BCG生菌の1mg群および2.5mg群に分け, 皮下投与と腫瘍内投与により腫瘍増殖抑制効果を比較検討した。これによるとBCG生菌投与群ではコートロール群に比較して腫瘍の縮小は認めたものの有意の差はなかった。しかし, 病理組織学的所見によればBCG生菌投与群の腫瘍細胞のほとんどが壊死化し, 大量の好中球の出現が認められ, これが腫瘍細胞の崩壊に関与しているのではないかと考えられた。またかかる変化は皮下投与よりも腫瘍内投与の方が強いように思われた。

A case of malignant pilomatricoma.

54歳女性の右前腕に生じたMalignant pilomatricomaの1例を報告した。臨床像は可動性良好な表面淡紅色の鶏卵大皮下腫瘤であり, 病理組織学的には, 真皮深層から皮下結合織内にかけて存在する境界明瞭な腫瘍でshadow cellとbasophilic cellからなり, 多数の核分裂像が認められる。本症は国内外において報告例が少なく, 極めて稀であると思われたので, これを報告するとともに若干の考察を加えた。

Cases of malignant lymphomas at the National Cancer Center. A study especially on tumor markers.

悪性リンパ腫の概念は, 近年の酵素組織化学や免疫学の発展の結果, 一新された。現在その分類については, なおいくつかのものが併用されており, 統一には至っていない。我々は国立がんセンターにおける皮膚悪性リンパ腫症例のうち主にmycosis fungoidesについて臨床的にまた免疫組織学的に検討を加えた。