豚の黒色腫の病理形態学的研究

沢谷, 廣志; Hiroshi, Sawaya

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豚の黒色腫の病理形態学的研究

https://az.repo.nii.ac.jp/records/3454

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Item type

学位論文 / Thesis or Dissertation(1)

公開日

2014-01-22

タイトル

豚の黒色腫の病理形態学的研究

タイトル

Patho-morphological Study on Porcine Melanomas

言語

jpn

資源タイプ

資源タイプ識別子

http://purl.org/coar/resource_type/c_46ec

資源タイプ

thesis

著者

沢谷, 廣志

Hiroshi, Sawaya

抄録

内容記述タイプ

Abstract

内容記述

家畜の黒色素性腫瘍は，多くの報告があり，獣医病理学の教科書にも，古くからその存在が記述されている。
　人医学に於ては，色素性母斑や黒色腫について，既に長期にわたり研究が続けられている。
　家畜の黒色腫は，老齢の芦毛馬や，コッカスパニエル種の犬にしばしば発見されているが，豚の黒色腫に関する報告は，ごくわずかのようである。
　これらは，有色肥育豚の悪性例に関する症例報告と，ヒトの animal model としてのミニ豚に関する一連の報告が主体をなしており，日本における家畜腫瘍の文献の集大成を行った佐伯（1978）によれば，1966年までの間に，わが国においては，豚の黒色腫に関する記載は無いとされている。
　著者は，共同研究者と共に，1974年，本邦ではじめて肥育豚の黒色腫を報告し，その後，約10年間にわたり，本病の連続的発生状況を日本獣医学会などに報告してきた。
　著者らの第一報の後，わが国においても，最近，いくつかの豚黒色腫に関する報告がなされつつある。
　本報告は，第一報の内容を基礎に，神奈川県下の5ケ所のと畜場における長期間の調査により得られた材料について，一連の研究を行ったものである。
　研究は，連続的に多発する本病に関し，その発生要因の追究と，すでに先人により示されているヒトとの比較を含む，いくつかの病理組織学的分類基準との適合性をふまえ，病理形態学的検討を行い，さらに臨床的側面からも若干の検討を加えた。
　検索材料は，1973年から1977年までの5年間に，1,910,889頭のと殺豚の中から得られた742例の黒色腫と，その後に得られた内臓転移悪性黒色腫9例を対象とした（Table 1.）。
I 　担腫瘍豚の検出状況
　調査対象に対する10万頭当り39頭、および多発農場（グループ）での10万頭当り最低163頭、最高473頭の年次別検出頻度は，高率，かつ持続的なもので，当地における豚の好発腫瘍中，第一位の腫瘍とみなされた。
　担腫瘍豚の品種は，Duroc種，または Hampshire種の混血豚を主とする，いずれも有色豚であったが，外国での文献には見当らないHampshire種41例の発生があり，これは我国での特徴の一つとみなされた。
　担腫瘍豚の中に，高率に発生した同腹豚の2例（6頭）が得られた（Fig. No.6）。
　野外調査の結果，多発農場では，担腫瘍豚の常時発生と多発血統の存在が確認された。
　多発農場からの種豚導入が明らかな農場での続発傾向は，著者らの助言による担腫瘍種豚，または担腫瘍種豚候補の積極的淘汰により，その後の発生が著明に減少した（Fig. No.3）。
　このことから，豚黒色腫の発生に関し，Nordby（1933）の記述と同様に遺伝的要因の関与が強く示唆された。
II　臨床的所見
　臨床的に，大半は特異な症状を示さなかったが，悪性例を中心とする若干例に，発育障害、交配能力低下，掻痒感など，臨床上着眼すべき点が示唆された。
III 発生部位
　原発巣はすべて皮膚で，全身性分布を示していたが，かなり多発性で，2ないし168個所の多発型108例を含み，1,243個の皮膚腫瘍が得られた。
　皮膚腫瘍の発生部位については，内臓転移型の頭頸部原発，多発型症例による特定部位への偏在，輪状白斑型の腰背部等被毛粗剛部での発生，および黒斑内腫瘍化型の下腹部等軟毛部皮膚での発生などの傾向が認められた。
　これらの所見は，文献的記載に乏しい注目すべき所見であった。
IV　病理学的所見
　原発巣の肉眼的所見は，腫瘍表面の外観，割面のサイズ，形態，性状など，症例により多彩であったが，大半は黒色部を有していた。
　しかしながら，剪毛によってはじめて発見される例や，表面の褪色した腫瘍が白毛部に生じた場合，発見がかなり困難であった。
　病理組織学的主要所見は，メラニンを富有する類円形，またはやゝ細長い上皮様細胞，紡錘形細胞，Melanophage，多核巨細胞など各種細胞による胞巣または渦紋形成，敷石状，柵状ないしビマン性増殖であった。
　大腫瘍型や内臓転移型には，ビ爛，潰瘍，中心の壊死，出血，石灰化が目立った。
　病変の出現部位は基底層上に限局するものから，深部下織に達するものまであり，接合性変化を主とするものが80%を占めた。
　病理組織学的には，WHOにより示されているいずれのタイプも認められたが，個々の所見は必らずしも一致していなかった。
　細胞診の所見は，標本中のメラニン顆粒の状態，担色素細胞の形態，炎症性細胞の関与の程度などを確認する上から，本病の検索にあたってかなり有効な手段であった。
V 　悪性度
　材料不備な29例を除き，病理組織学的に十分に検索した713例のうち，190例（26.6%）は良性，523例（73.4%）は悪性黒色腫と診断され，本病の悪性傾向が明られであった（Table. 6）。
　濃厚な黒斑内に生じた例は，ヒトでの表在拡大型悪性黒色腫（superficial－spreading－melanoma）に類似し，段階的各所見がみられたことから，本病の進行過程が示唆された。
　良性と診断した例の中には，ヒトでの junctional nevus や，compound nevus の所見にほぼ一致するものがあった。
　これらの例では，母斑（nevus）の言葉を用いることも可能の感を受けたが，Millikanら（1974）の示す肉眼所見と一致しない例もあり，単純には比較出来なかった。
　皮膚腫瘍周囲に，白毛と輪状の白斑を持つ12例は良性例が主で，ヒトでのSutton's－halo－nevus，およびミニ豚でのperipheral dipigmentation（Millikan et al : 1974）の所見に類似していた。
　原発巣の潰瘍化例のうち89%は組織学的に悪性例であったことから，潰瘍化と悪性度は平行する重要な所見と思われた。
　原発巣のサイズと悪性度について，Mulligan（1963）は，犬の場合，長径1.0cm以下は良性，2.5㎝以上は通常悪性としているが，組織学的検査による悪性例や，リンパ節転移例の出現する事実からみると，著者は原発巣の深達度1mm以上を悪性例出現の境界レベルとし得ると判断した。
　即ち，動物が生き長らえた場合，他の動物と同様の経過をたどる可能性が高く，Nomuraら（1974）の指摘のごとく，大多数は潜在的に悪性であると結論された。
VI　発生母地と転移
　豚黒色腫の発生母地について，主として皮膚の接合性変化が先行するものであったが，末梢神経との関係も示唆された。
　黒色腫の悪性化による転移については外科的刺激の関連も指摘されているが（Thirloway et al : 1977），著者の症例中にも，標識のため施した耳環，および耳刻装着部位より内臓転移型が3例存在し，若齢時の外科的措置は，色素斑の存在に充分注意して実施すべきであると考えられた。
　転移のルートは，直接蔓莚，リンパ行性，および血行性の所見が観察された。
　リンパ節転移は，全検索例の42.3%にみられ，また内臓転移型は，29例（10万頭当り1頭）検出され，いずれも高頻度なものであった。
　転移性病変の臓器別分布から，肺，肝，脳，脊髄，躯幹筋などが，文献記載同様，本病における転移の好発臓器とみなされた。
　支配リンパ節に黒色素性病変を持つ例については，全身観的詳細な検索が絶対必要であった。
　以上のごとく，外国でのミニ豚と，Duroc種の悪性例を除けば，従来報告の乏しかった豚の黒色腫に関し，著者は，我国ではじめて多数の症例を取扱い、比較検討を行った結果，数多くの病理学的新知見のみならず，臨床的にも多くの新知見を得た。
　今回の研究で得られた結果の大判は，著者と共同研究者による報告（1974）以前には記載されていなかったもので，黒色素性腫瘍の比較病理学について，いくつかの基礎的情報を提供するものと信ずる。
(以下図表)

Abstract

内容記述タイプ

Other

内容記述

Occurrence of melanotic tumors of domestic animals have been reported and described in the textbook of veterinary pathology since the early time of 20th century as well as nevi and melanomas of human beings.
Melanomas are frequently encountered and reported in old gray-horses and Cocker-Spaniel breed dogs, but a small number of porcine melanoma cases have been described in these several decades in fattening pigs with colored skin, excepting a serial paper on melanomas of miniature pigs raised up as an experimental animal.
According to Saheki (1978), there were few reports of melanomas of pigs in Japan until the author and coworkers published their first report on melanomas of pigs in 1972.
The author collected and examined a lot of swine melanoma cases in these ten years and the results have been represented on the annual meetings of the Japanese society of veterinary science.
This paper is the first detailed report on it, including a long term survey carried out at abattoirs and many pig farms and pathological observations in relation to melanotic tumors in man and other animals.
During five years survey from 1973 to 1977, the author detected 742 melanoma cases among 1,910,889 pigs slaughtered for meat; these cases gave the basis to estimate the occurrence rate and were the main materials for histopathological observation, however, several interesting cases were collected after this period and examined together.
Histological classification was mainly according to the international histological classification of tumors in domestic animals in relation to that of human neoplasms proposed by Weiss and Frese (1974).
l. Occurrence rate and some clinical findings;
Average rate of tumor occurrence was estimated about 39 cases per 100,000 pigs slaughtered, while it varied from 163 to 473 cases per year in the most prevalent farm "S" and/or the farms with some relations to that farm.
This high rate of occurrence had continued during the survey and melanomas were the most common neoplasm among pigs in this district, in which included the first area for introducing Duroc-Jersey breed pigs in this country.
Tumor bearers mainly composed of hybrid pigs covered with deeply colored skin derived from Duroc-Jersey and/or Hampshire breed, whereas 41 cases were considered to be pure Hampshire.
Familial incidence of melanoma was not uncommon.
The survey clarified frequent occurrence of the tumor in prevalent farms and it was caused by the pigs for breeding introduced from such prevalent farms.
Some farmers rejected the introduction of these tumor bearing pigs from their breeding herd according to the author's recommendation and thereafter succeeded in decreasing the occurrence rate of the tumor.
These facts would prove the presence of the genetical factors influencing upon the genesis of this tumor as seen in the Nordby's description (1933).
Most of these melanoma bearing pigs showed little clinical abnormalities while a small number of malignant cases was accompanied by the failure of growth, sterility and itching.

2. Original sites of tumors;
All original tumors were first found in the skin and then distributed in every portion of the body.
Multiple tumors were fairly common, e.g. 108 multiple cases consisted of two to 168 tumors.
Total number of cutaneous tumors examined reached 1,243 cases.
There were some relationships between original site and nature of the tumor, e.g. malignant melanoma with visceral metastasis was frequently found in the head to neck region, annular white spot type melanoma was frequently seen in the back to loin, and black spot type melanoma was frequent in lower abdomen. Tumor masses were often preferably located in the special region of the skin among multiple cases.
These relations between the site of tumor and its nature were
not described previously.

3. Gross pathological findings;
Gross findings of the original tumors were varied respectively, although almost of all tumors showed deeply pigmented lesions.
The covering skin or the tumor surface were not always pigmented and it was difficult to find the tumor located in the deep portion and covered with less colored intact skin or the mass with grey to white discoloration on its surface occurred in the whitish skin areas.
Ulceration of the covering skin suggested its malignant nature, i.e. 89% of ulcerated tumors were histopathologically diagnosed as malignant melanoma.
Thus, the author considered this finding might be an important criterion of malignant melanoma of swine.
The depth of the tumor growth in the original site was another remarkable finding suggesting its nature as Mulligan (1963) stressed that the size of tumor was indicative for malignancy.
The author concluded that 1mm depth was the borderline, over which it should be malignant to become.
Lymph node metastasis was noted in 42.3% of all tumors examined and malignant melanomas with visceral metastasis were summed up to 29 cases; it was one case per 100,000 pigs slaughtered.
The distribution of the secondary tumors was varied; however, the secondaries were frequently found in lung, liver, cerebro-spi-
nal tissue and skeletal muscles in this order.
Accordingly, for confirming the malignancy of the tumor cases with the pigmented regional lymph node it must need to examine these preferable organs histopathologically.

4. Microscopic findings;
Cytological examination of the tumors of skin of pigs was useful for detection of this disease, for it was able to know the size, shape and distribution or situation of the melanin granules, morphology of the pigmented cell and the degree of inflammatory reactions, although melanin granules were sometimes so abun-
dant as to obscure the nucleus.
Histopathological examination was carried out on 713 cases.
All types of melanomas according to WHO classification by Weiss and Frese were found in them, but there were some difference in details.
The reason of this difference was obscure, while WHO classification is mainly based on the investigations of canine melanomas.
Benign melanoma was 190 cases (26.6% of total cases), while　 malignant melanoma was 523 cases(73.4%) .
That is, malignant melanoma was much more frequent than benign tumor in pigs.
Melanomas originated in deep black spot had a resemblance to “Superficial-spreading-melanoma” of human skin and sequential patterns were observed among many cases, suggesting the developmental stage and histogenesis of porcine melanomas of skin.
Porcine benign melanomas frequently included the rather small tumor masses and their structures were almost similar to junctional nevus and/or compound nevus in human skin.
Among these benign neoplasms, it was supposed to be able to use the term "nevus", but there were some differences between the results of this study and the description of Millikan, et al (1974).
Twelve cases of skin tumors with annular white spot and white hairs were the benign melanomas like Sutton's halo-nevus of man and the porcine melanomas with peripheral depigmentation reported by Millikan et al(1974) , excepting a few cases.
Small cutaneous tumors over 1mm depth included several malignant cases, although they were apparently benign under naked eye.
This fact suggested that these tumors were potentially malignant and would develop to the widespread lesions as well as the large malignant tumors with visceral metastasis mentioned above, if animals survived for many years.
The most preferential site of melanoma was supposed to be the junctional portion, but the tumors were sometimes related to the peripheral nerve endings.
5. Malignant manifestation and metastasis;
In this series, the author found three cases of malignant melanoma originated in the auricle with ear tag, probably developed from a chronic irritation after the setting of it.
Direct extension, metastasis via lymphatics and blood vessels
were proved as the route of tumor dissemination histopathologi-
cally . 　　　　　　　　　　　　
Thus, almost of all results obtained in this study provided new findings on porcine melanomas in Japan which never had been described before and will provide some fundamental data for the comparative pathology of melanotic tumors.
Occurrence of melanotic tumors of domestic animals have been reported and described in the textbook of veterinary pathology since the early time of 20th century as well as nevi and melanomas of human beings.
Melanomas are frequently encountered and reported in old gray-horses and Cocker-Spaniel breed dogs, but a small number of porcine melanoma cases have been described in these several decades in fattening pigs with colored skin, excepting a serial paper on melanomas of miniature pigs raised up as an experimental animal.
According to Saheki (1978), there were few reports of melanomas of pigs in Japan until the author and coworkers published their first report on melanomas of pigs in 1972.
The author collected and examined a lot of swine melanoma cases in these ten years and the results have been represented on the annual meetings of the Japanese society of veterinary science.
This paper is the first detailed report on it, including a long term survey carried out at abattoirs and many pig farms and pathological observations in relation to melanotic tumors in man and other animals.
During five years survey from 1973 to 1977, the author detected 742 melanoma cases among 1,910,889 pigs slaughtered for meat; these cases gave the basis to estimate the occurrence rate and were the main materials for histopathological observation, however, several interesting cases were collected after this period and examined together.
Histological classification was mainly according to the international histological classification of tumors in domestic animals in relation to that of human neoplasms proposed by Weiss and Frese (1974).
l. Occurrence rate and some clinical findings;
Average rate of tumor occurrence was estimated about 39 cases per 100,000 pigs slaughtered, while it varied from 163 to 473 cases per year in the most prevalent farm "S" and/or the farms with some relations to that farm.
This high rate of occurrence had continued during the survey and melanomas were the most common neoplasm among pigs in this district, in which included the first area for introducing Duroc-Jersey breed pigs in this country.
Tumor bearers mainly composed of hybrid pigs covered with deeply colored skin derived from Duroc-Jersey and/or Hampshire breed, whereas 41 cases were considered to be pure Hampshire.
Familial incidence of melanoma was not uncommon.
The survey clarified frequent occurrence of the tumor in prevalent farms and it was caused by the pigs for breeding introduced from such prevalent farms.
Some farmers rejected the introduction of these tumor bearing pigs from their breeding herd according to the author's recommendation and thereafter succeeded in decreasing the occurrence rate of the tumor.
These facts would prove the presence of the genetical factors influencing upon the genesis of this tumor as seen in the Nordby's description (1933).
Most of these melanoma bearing pigs showed little clinical abnormalities while a small number of malignant cases was accompanied by the failure of growth, sterility and itching.

2. Original sites of tumors;
All original tumors were first found in the skin and then distributed in every portion of the body.
Multiple tumors were fairly common, e.g. 108 multiple cases consisted of two to 168 tumors.
Total number of cutaneous tumors examined reached 1,243 cases.
There were some relationships between original site and nature of the tumor, e.g. malignant melanoma with visceral metastasis was frequently found in the head to neck region, annular white spot type melanoma was frequently seen in the back to loin, and black spot type melanoma was frequent in lower abdomen. Tumor masses were often preferably located in the special region of the skin among multiple cases.
These relations between the site of tumor and its nature were
not described previously.

3. Gross pathological findings;
Gross findings of the original tumors were varied respectively, although almost of all tumors showed deeply pigmented lesions.
The covering skin or the tumor surface were not always pigmented and it was difficult to find the tumor located in the deep portion and covered with less colored intact skin or the mass with grey to white discoloration on its surface occurred in the whitish skin areas.
Ulceration of the covering skin suggested its malignant nature, i.e. 89% of ulcerated tumors were histopathologically diagnosed as malignant melanoma.
Thus, the author considered this finding might be an important criterion of malignant melanoma of swine.
The depth of the tumor growth in the original site was another remarkable finding suggesting its nature as Mulligan (1963) stressed that the size of tumor was indicative for malignancy.
The author concluded that 1mm depth was the borderline, over which it should be malignant to become.
Lymph node metastasis was noted in 42.3% of all tumors examined and malignant melanomas with visceral metastasis were summed up to 29 cases; it was one case per 100,000 pigs slaughtered.
The distribution of the secondary tumors was varied; however, the secondaries were frequently found in lung, liver, cerebro-spi-
nal tissue and skeletal muscles in this order.
Accordingly, for confirming the malignancy of the tumor cases with the pigmented regional lymph node it must need to examine these preferable organs histopathologically.

4. Microscopic findings;
Cytological examination of the tumors of skin of pigs was useful for detection of this disease, for it was able to know the size, shape and distribution or situation of the melanin granules, morphology of the pigmented cell and the degree of inflammatory reactions, although melanin granules were sometimes so abun-
dant as to obscure the nucleus.
Histopathological examination was carried out on 713 cases.
All types of melanomas according to WHO classification by Weiss and Frese were found in them, but there were some difference in details.
The reason of this difference was obscure, while WHO classification is mainly based on the investigations of canine melanomas.
Benign melanoma was 190 cases (26.6% of total cases), while　 malignant melanoma was 523 cases(73.4%) .
That is, malignant melanoma was much more frequent than benign tumor in pigs.
Melanomas originated in deep black spot had a resemblance to “Superficial-spreading-melanoma” of human skin and sequential patterns were observed among many cases, suggesting the developmental stage and histogenesis of porcine melanomas of skin.
Porcine benign melanomas frequently included the rather small tumor masses and their structures were almost similar to junctional nevus and/or compound nevus in human skin.
Among these benign neoplasms, it was supposed to be able to use the term "nevus", but there were some differences between the results of this study and the description of Millikan, et al (1974).
Twelve cases of skin tumors with annular white spot and white hairs were the benign melanomas like Sutton's halo-nevus of man and the porcine melanomas with peripheral depigmentation reported by Millikan et al(1974) , excepting a few cases.
Small cutaneous tumors over 1mm depth included several malignant cases, although they were apparently benign under naked eye.
This fact suggested that these tumors were potentially malignant and would develop to the widespread lesions as well as the large malignant tumors with visceral metastasis mentioned above, if animals survived for many years.
The most preferential site of melanoma was supposed to be the junctional portion, but the tumors were sometimes related to the peripheral nerve endings.
5. Malignant manifestation and metastasis;
In this series, the author found three cases of malignant melanoma originated in the auricle with ear tag, probably developed from a chronic irritation after the setting of it.
Direct extension, metastasis via lymphatics and blood vessels
were proved as the route of tumor dissemination histopathologi-
cally . 　　　　　　　　　　　　
Thus, almost of all results obtained in this study provided new findings on porcine melanomas in Japan which never had been described before and will provide some fundamental data for the comparative pathology of melanotic tumors.

学位名

獣医学博士

学位授与機関

学位授与機関名

麻布大学

学位授与年月日

1982-12-01

学位授与番号

乙第206号

著者版フラグ

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出版タイプResource

http://purl.org/coar/version/c_ab4af688f83e57aa

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豚の黒色腫の病理形態学的研究

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× Hiroshi, Sawaya

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