以形態病理學及免疫組織化學染色技術探討犬血管周圍細胞瘤之組織來源

Abstract

犬血管周圍細胞瘤 (Canine hemangiopericytoma; CHP)為一個好發於中老年犬的皮膚軟組織腫瘤，多發生於四肢關節處之皮下組織。CHP具有組織病理形態，免疫組織化學染色以及電子顯微鏡之特徵，並且都建議為血管周圍細胞來源的腫瘤。但是其組織來源仍未定，因此於世界衛生組織將CHP歸類為皮膚及軟組織的未分類的腫瘤。世界衛生組織將人類血管周圍細胞瘤 (Human hemangiopericytoma; HP) 以及人類肌肉樣細胞瘤 (Human myopericytoma; MP) 分別歸類為軟組織腫瘤之纖維芽母細胞性/肌肉樣纖維芽母細胞性腫瘤以及血管周圍性腫瘤。在本次研究中，共收集18例CHP以及18例HP，並且進行比較其組織型態學及免疫染色之差異。CHP多發生於7歲到12歲，佔 (6 7 %; 12/18)，常見於雌性犬隻，佔 (67 %; 12/18)，中大型犬所佔的比例為最高，其中以混種犬所佔的比例最高，為 (33 %; 6/18)，多發生於在四肢的關節或腳掌處為最四肢的關節或腳掌處為最多，發生率為 (56 %; 10/18)。CHP與MP之生長形態多呈現血管周圍性旋渦狀排列到細胞密度較高的打轉狀形態，常可見腫瘤細胞排列於微血管或中小型血管外圍，且其細胞形態與大小較為相似。HP則呈現實心狀到片狀之排列，常可見具有分枝，類似鹿角狀的微血管，其腫瘤細胞較小，橢圓形、圓形到梭形，與CHP之差異性較大。CHP的免疫染色結果分別為vimentin, 100 % (18/18)、NSE, 100 % (18/18)、S-100, 78 % (14/18)、desmin, 67 % (12/18)、α-SMA, 61 % (11/18) 、HHF-35, 56 % (10/18) 、neurofilament, 33 % (6/18)、Factor VIII, 28 % (5/18)、Collagen IV, 6 % (1/18)、laminin, 0 % (0/18) 以及 NGFR, 0 % (0/18)。HP的免疫染色結果分別為vimentin, 100 % (18/18)、Factor VIII, 78 % (14/18)、HHF-35, 17 % (3/18) 、α-SMA, 11 % (2/18) 、desmin, 0% (0/18)、Collagen 4, 0 % (0/18)以及laminin, 0% (0/18)。根據此研究免疫染色輪廓之結果，以及MP相關研究報告顯示，CHP與MP對於肌肉相關之抗體之陽性率較高。超顯微結構下，腫瘤細胞其排列方式由緊密到疏鬆排列，可見具有長短不一的細胞突起、不規則的基底膜，擴張的粗糙內質網及大小不一的胞飲小泡在細胞質內，少量的微絲束以及中間絲的結構。根據此研究之結果得知，無論在腫瘤發生部位、組織病理形態學、免疫組織化學染色結果以及超顯微結構的特徵，CHP與HP具有明顯的差異性，反而與MP之特徵較為相近，此結果可間接證實CHP之腫瘤細胞來源與MP的腫瘤細胞之來源較為相似，可能為血管周圍細胞來源並具有類肌肉細胞的分化。

Canine hemangiopericytoma (CHP) is a soft tissue tumor of skin, often found in middle to old age of dogs, and arises in the subcutis of joint and limbs. CHP with morphopathological, immunohistochemical and electronic microscopical studies, suggests this is pericytic origin. The actual histogenesis is uncertain, and classified into unclassified tumor of soft tissue of skin in WHO. Human hemangiopericytoma (HP) and human myopericytoma (MP) respectively classified as fibroblastic/myofibroblastic and pericytic tumor by WHO. A total of 18 CHP were used in this study and 18 HP were also collected to compare with CHP. The peak incidence of CHP was between 7 to 12 years (67 %; 12/18) of age, and sex predilection was male (67 %; 12/18). Most common breed affected was mongrel (33 %; 6/18). Most of the cases were located in the subcutis of limb, especially in joint and foot (56 %; 10/18). Histopathologically, CHP revealed perivascular whorls of fusiform and ovoid tumor cells, interlacing and storiform pattern, and concentric arrangement with capillary and medium to small blood vessels, and similar to MP. But, HP characterized small ovoid, round to spindle tumor cells arranged in solid to sheets and surrounding thin walled, branching, stag-horn pattern of dilated blood vessels. The IHC profile of CHP showed vimentin (100 %; 18/18), NSE (100 %; 18/18), S-100 (78 %; 14/18), desmin (67 %; 12/18), α-SMA (61 %; 11/18), HHF-35 (56 %; 10/18), neurofilament (33 %; 6/18)、Factor VIII (28 %; 5/18)、Collagen IV (6 %; 1/18)、laminin (0 %; 0/18) and NGFR (0 %; 0/18). CHP showed vimentin (100 %; 18/18)、Factor VIII (78 %; 4/18), HHF-35 (17 %; 3/18), α-SMA (11 %; 2/18), desmin (0%; 0/18), Collagen IV (0 %; 0/18) and laminin (0%; 0/18). IHC profiles of CHP resembled in MP that both they expressed in muscle marker. Ultrastructurally, the tumor cells were arranged in compact to loose with irregular cell processes, basal lamina, dilated rough endoplasmic reticulum, and variable sized pinocytes and microfilaments in cytoplasm. In conclusion, features of morohopathology, IHC profile and ultrastructural findings reveal obvious divergence between CHP and HP and resemble MP, so we suggest that histogenesis of CHP is pericyte with myoid differentiation.