外周原始神经外胚叶瘤/尤因肉瘤临床病理学

目的:研究原始神经外胚叶瘤(PNET)/尤因肉瘤的(EWS)的诊断、鉴别诊断.方法:41例病人按传统病理学分为3类,并用免疫组织化学两步法检测CD99、NSE、S-100蛋白、Syn、Vim、LCA、Des、Myo抗体的表达.结果:(1)41例病人有27例PNET,8例EWS和6例Askin瘤.(2)免疫表型:CD99有87.8%强阳性表达,NSE 53.7%,S-100蛋白22%,Syn 4.9%,vim 41.5%,统计结果显示CD 99强阳性表达与NSE、S-100蛋白、Syn、Vim强阳性表达差异有显著性(P<0.01).(3)PNET、EWS、Askin瘤对各种抗体的阳性表达差异无显著性(P>0.05).结论:(1)PNET、EWS、Askin瘤属同一肿瘤家族.(2)用组织学、免疫组织化学可与其他小圆细胞肿瘤进行鉴别诊断.     

软骨黏液样纤维瘤和软骨母细胞瘤的临床病理差异与组织发生关系

目的 探讨软骨黏液样纤维瘤(chondromyxoid fibroma,CMF)和软骨母细胞瘤(chondroblastoma,CB)的临床病理差异与组织发生的关系.方法 利用免疫组化EnVision两步法对4例CMF和10例CB行S-100蛋白、Ⅰ～Ⅲ型胶原、MSA,SMA和CD34染色,并对比观察.结果 4例CMF平均年龄为24岁,2例发生于长骨干骺端,2例位于肩胛骨;在4例CMF的小叶间富于细胞区均有数量不等的CB样分化区域;免疫组化标记2例S-100蛋白阳性,各有2例可检测到局灶性表达的Ⅱ型和Ⅰ、Ⅲ型胶原,3例小叶周边区肿瘤细胞表达SMA和MSA.10例CB平均年龄19岁,8例发生于长骨骨骺,1例位于坐骨,1例位于髂骨;免疫组化标记7例S-100蛋白弥漫阳性,2例有局灶性的Ⅱ型胶原表达,3例有多少不等的Ⅰ、Ⅲ型胶原表达,4例部分肿瘤细胞表达SMA和MSA.结论 CMF和CB具有不同的临床病理特征,但CMF中含CB分化的区域,两者均有软骨母细胞和纤维母细胞/肌纤维母细胞的免疫表型,并在细胞外基质中可检测到相似的胶原表达,提示两者在组织发生上有一定联系.     

肢端黏液样炎性纤维母细胞肉瘤2例及文献复习

目的探讨肢端黏液样炎性纤维母细胞肉瘤的临床病理学特征及鉴别诊断。方法对2例发生在下肢末端的黏液样炎性纤维母细胞肉瘤进行光镜观察和免疫组化标记，并复习文献。结果2例发生在下肢末端的病程较长的渐进性肿块，术后局部复发。镜检：病变呈多结节状，边界不清；黏液样基质中见数量不等的各类炎细胞浸润，散在或灶性分布梭形、奇异形和多空泡状脂肪母细胞样3种形态的瘤细胞。免疫表型：肿瘤细胞Vim弥漫阳性，CD68和CD34灶性阳性，CK、SMA、HHF-35、S-100蛋白、CD45、CD45R0、CD15、CD30均阴性。结论此病病程较长，术后易局部复发，是一种低度恶性的肿瘤。鉴于病变黏液样基质及各类炎细胞浸润的背景较为突出，而特征性的瘤细胞稀疏，应注意与炎症性病变或具有相似组织形态的良性或恶性肿瘤鉴别。     

骨小细胞恶性肿瘤34例病理形态学研究

目的 研究骨小细胞恶性肿瘤(SCMT)的病理形态和免疫组化特点。方法 应用免疫组化SP法对34例SCMT进行组织学观察。结果 34例SCMT中22例为弥漫型非霍奇金恶性淋巴瘤，其中21例B细胞性，1例T细胞性；瘤组织表达CD45(LCA)、CD20(L26)或C1345RO(UCHL—1)。7例浆细胞肿瘤，其中5例为多发性骨髓瘤、2例为孤立性浆细胞瘤，表现为单一的不同分化程度的肿瘤性浆细胞；免疫组化示6例CD38( )。2例Ewing肉瘤显示排列密集、大小较一致的圆形细胞；肿瘤表达CD99和Vim。1例小细胞骨肉瘤，肿瘤由丰富密集的小细胞和网格状的骨样组织组成，瘤细胞Vim阳性。1例间叶性软骨肉瘤示富于血管的圆形或梭形细胞和透明软骨；瘤细胞表达Vim，软骨细胞表达S—100蛋白。1例小细胞癌示小细胞紧密片巢状排列，表达CK和EMA。结论 骨SCMT组织学类型各有不同的病理形态和免疫组化特征，结合临床和X线表现可作出正确的病理诊断。     

外周原始神经外胚肿瘤／尤因肉瘤临床病理学

目的：研究原始神经外胚叶瘤（PNET）／尤因肉瘤的（EWS）的诊断,鉴别诊断。方法：41例病人按传统病理学分为3类,并用免疫组织化学两步法检测CD99,NSE,S－100蛋白,Syn,VIm,LCA,Des,Myo抗体的表达。结果：（1）41例病人有27例PNET,8例EWS和6例Askin瘤。（2）免疫表型,CD99有87．8％强阳性表达,NSE53．7％,S－100蛋白22％,Syn4.9%,vim41.5%,统计结果显示CD99强阳性表达与NSE,S-100蛋白,Syn,Vim强阳性表达差异有显著性（P＜0．01）。（3）,PNET,EWS,Askin瘤对各种抗体的阳性表达差异无显著性（P＞0．05）,结论：（1）PNET,EWS,Askin瘤属同一肿瘤家族,（2）用组织学,免疫组织化学可与其他小圆细胞肿瘤进行鉴别诊断。     

软骨样脂肪瘤1例报道及文献复习

目的探讨软骨样脂肪瘤的临床、病理学特点和鉴别诊断。方法报道1例右小腿软骨样脂肪瘤的临床资料、光镜、组化、免疫组化及电镜观察结果,结合文献讨论。结果镜下见肿瘤由3种成分以不同比例混合构成:①较成熟脂肪细胞体积小的单泡状和多泡状脂肪母细胞,胞质淡染为主,少数细胞呈嗜酸性,核形多样,无异型性及核分裂象,排列成片状和巢状;②脂肪母细胞间黏液透明性软骨样基质;③多少不等的成熟脂肪细胞。PAS染色见脂肪母细胞的胞质内含许多可被淀粉酶消化的深红染颗粒,提示存在糖原。AB染色见黏液透明性软骨样基质呈阳性反应,并部分耐透明质酸酶消化,提示含有硫酸软骨素。脂肪母细胞和成熟脂肪细胞表达S-100蛋白,其中脂肪母细胞对S-100蛋白的表达与脂肪母细胞分化成熟程度相关。电镜观察可见处于不同发育阶段的脂肪母细胞,脂肪母细胞周围被絮状的软骨样基质围绕。结论软骨样脂肪瘤是一种十分罕见的良性脂肪细胞肿瘤的特殊类型,具有独特的组织学形态,应注意与黏液型脂肪肉瘤和骨外黏液样软骨肉瘤等肿瘤鉴别。     

胫骨皮质旁软骨肉瘤1例报道及文献复习

目的：了解皮质旁软骨肉瘤的临床病理特征、诊断及鉴别诊断要点。方法：报道1例胫骨皮抽旁软骨肉瘤临床和病理改变，结合文献对该肿瘤的临床表现、病理形态学特征及诊断和鉴别诊断要点进行讨论。结果：皮质旁软骨肉瘤大体呈结节状，切面分叶状、瓷白色半透明，有砂砾感。镜下肿瘤主要为分化良好的透明软骨成分，由纤细的纤维束分割，或由化生的内小梁包裹，可见软骨内钙化和骨化，可见灶性区黏液变性，缺乏肿瘤性骨样基质，免疫组织化学标记显示肿瘤细胞Vim、S-100蛋白阳性，PCNA少数细胞阳性。结论：皮质旁软骨肉瘤是罕见的恶性程度较低的软骨肉瘤。     

色素型隆突性皮肤纤维肉瘤8例光镜、免疫组织化学及电镜观察

目的 探讨色素型隆突性皮肤纤维肉瘤(DFSP)临床病理特征和鉴别诊断。方法 对8例色素型DFSP进行了光镜和免疫组化染色观察，其中4例做电镜观察。结果 色素型DFSP患者的年龄、性别、肿瘤部位和肿瘤生长方式与普通型DFSP相同。随访结果3例发生复发，无1例发生转移。4例肿瘤切面见浅黑色或黑色斑。所有病例既可见典型的DFSP组织形态学特征，同时又见散在性分布、数量多少不等的黑色素细胞。本组6例瘤组织显示普通型DFSP图像，2例部分区域显示纤维肉瘤型DFSP图像，偶可见血管壁平滑肌增生形成的肌样结节和黏液样变性区。Fontana染色黑色素细胞呈阳性，Perls染色则为阴性。梭形瘤细胞呈vim和CD34阳性，CD34阳性具有一定辅助诊断价值，S-100蛋白和NSE阴性；黑色素细胞呈S-100蛋白和Vim阳性；纤维肉瘤型DFSP区Ki—67阳性表达率高于普通型DFSP区。电镜观察：可见梭形纤维母细胞样细胞和含有许多成熟黑色素小体黑色素细胞。结论 色素型DFSP是一种少见的DFSP亚型，临床病理特征与普通型DFSP对比有许多共同之处，需与动脉瘤样型纤维组织细胞瘤、弥漫性神经纤维瘤、细胞性蓝痣和促结缔组织增生性黑色素瘤鉴别。     

间叶性软骨肉瘤6例临床病理分析

目的 探讨间叶性软骨肉瘤(mesenchymal chondrosarcoma,MC)的临床特点、病理特征、诊断及鉴别诊断.方法 采用HE及免疫组化EnVision两步法对6例MC进行观察,并复习相关文献.结果 6例MC分别位于股骨、骶骨、肱骨、锁骨、颈部和腹股沟.临床表现主要是疼痛和肿胀.影像学表现与普通软骨肉瘤无明显差别.组织学显示肿瘤由原始未分化小细胞和分化较成熟的透明软骨小岛构成,即双相图像.免疫组化显示未分化小细胞CD99呈不同程度的膜阳性,vimentin也有阳性表达,软骨区S-100蛋白可有阳性表达.结论 MC是一种少见的高度恶性肿瘤,其诊断要点是在未分化的小细胞区找到分化较成熟的软骨组织,结合临床资料、免疫组化等特点进行诊断.     

乳腺上皮样型管周间质肉瘤病理特征及与叶状肿瘤比较观察

目的 探讨乳腺上皮样型管周间质肉瘤的临床病理特点及与叶状肿瘤的关系。方法 采用HE、特殊染色、免疫组化染色(CK，EMA，S-100蛋白，SMA，Vim，Des，MG，CD34，CD99，CD117，PR，HMB45)对1例乳腺上皮样型管周间质肉瘤与5例叶状肿瘤(良性、交界性各1例，恶性3例)做比较性观察。结果 乳腺管周间质肉瘤(上皮样型)有独特的镜下图像：①显著的多角形(上皮样)细胞绕导管或小管的上皮肌上皮层呈间质性增生，无叶状结构；②组织学模式有袖套状、花冠状、菊形团状、结节状、融合结节状和片状浸润；③瘤细胞形态有：多角形(大、小)、柱状和梭形。多角形细胞呈上皮样形态，异型明显，核分裂象多见(10～30个／10HPF，个别区域达6个／1HPF)，病理性核分裂象易见，在浸润灶内见肿瘤性坏死；④瘤细胞Vim弥漫阳性、EMA灶性阳性、CD99和CD117灶性弱阳性、CD34少数阳性，CK、SMA、S-100蛋白、Des、MG、PR、HMB45均阴性。5例叶状肿瘤均具备叶状结构、间质过度增生、细胞密集(异质性分布)、核分裂象2～10个／10HPF等诊断要素。在3例恶性叶状肿瘤中，2例有极少的上皮样袖套状病灶，2例有梭形细胞袖套状病灶。结论 乳腺上皮样型管周间质肉瘤是一种极罕见的恶性纤维上皮肿瘤亚型，它可能是恶性叶状肿瘤的最早期病变，也可能是一种独特的类型。     

肺原发性软骨肉瘤2例及文献复习

目的：探讨肺原发性软骨肉瘤的临床病理特征及组织发生。方法：通过ＨＥ、组化及免疫组化观察２例肺原发性软骨肉瘤,并复习文献。结果：肿瘤由粘液亲基质和疏网状结构的梭形细胞及软骨母细胞组成,例２还存在幼稚小圆细胞,三种细胞梯度移行。组化染色显示ＡＢ（ｐＨ２．５）、ＴＢ（ｐＨ４．０）阳性。免疫组化染色显示梭形细胞及软骨母细胞Ｓ－１００蛋白、ｖｉｍｅｎｔｉｎ和ＮＳＥ阳性,例２Ｓｙｎ阳性。小圆细胞ＣＤ９９、Ｓ－     

Chondroblastoma of the temporal bone: a clinicopathologic study of five cases

Chondroblastoma is a rare benign bone tumor. It commonly affects the epiphysis of long bones during the second and third decades of life. Chondroblastoma of the temporal bone is extremely rare. We reviewed five cases of chondroblastoma arising in the temporal bone. Four cases were female and one was male. The ages ranged from 41 to 60 years (mean, 53.6 years). All cases involved the temporal bone. Three involved the left side and two the right. Chief complaints were long-standing localized pain and hearing difficulty. A sharply demarcated lobulated mass was the main radiological finding. Microscopic findings were those of chondroblastoma of usual locations. Two cases showed aneurysmal bone cyst-like areas. Immunohistochemical studies for CD34, CD99, S-100 protein and cytokeratin were performed. Tumor cells were diffusely positive for S-100 protein in three cases and weakly positive for cytokeratin in one case. CD34 and CD99 were negative in all cases. In summary, chondroblastoma of the temporal bone is rare and occurs in older age group than reported cases of chondroblastoma of the usual location in the literature.     

Spindle cell epithelioma of the vagina shows immunohistochemical staining supporting its origin from a primitive/progenitor cell population

Spindle cell epitheliomas of the vagina (SCEVs) coexpresses epithelial and mesenchymal markers and were first described as a "mixed tumors of the vagina." However, unlike mixed tumors of other organs, which are believed to originate from myoepithelial cells, SCEVs neither immunohistochemically nor ultrastructurally show features of myoepithelial cells. The present expanded battery of immunohistochemical stains is presented on this rare tumor, including cytokeratin AE1/AE3, CK7, CK20, S100 protein, epithelial membrane antigen, alpha-smooth muscle actin, desmin, CD34, CD99, Bcl-2, vimentin, estrogen and progesterone receptors, and Ki-67. There was minimal expression of alpha-smooth muscle actin and negative staining with S100 protein, with coexpression of cytokeratins and vimentin and expression of estrogen and progesterone receptors, as previously reported in SCEVs. In addition, diffuse expression of CD34, CD99, and Bcl-2 immunohistochemical stains was found, which has not previously been reported. The coexpression of CD34, CD99, and Bcl-2 in SCEVs is consistent with its origin from a primitive/progenitor cell population.     

Immunohistochemical findings in embryonal small round cell tumors with molecular diagnostic confirmation.

The diagnosis of pediatric tumors relies heavily on immunohistochemical staining of small tissue biopsies, since many entities share a "small blue cell" phenotype. More recently, molecular genetic analysis for detection of specific gene fusion products has become available. With the increased use of such molecular techniques, the authors have noted that tumors with proven molecular diagnoses can exhibit unusual patterns of immunohistochemical staining. This study examines pediatric tumors with a "small blue cell" phenotype in which molecular diagnoses were available where applicable. A panel of immunohistochemical stains was performed (S100, CD56, NB84, CD99 [MIC2], Bcl-2, CD117, CD34, desmin, MNF116, and WT1). In the 370 sections from 37 cases, all primitive neuroectodermal tumors, with and without the presence of t(11;22), demonstrated uniform membranous membrane staining with CD99 (MIC2) and focal staining with CD56, NB84, MNF116, and WT1. All rhabdomyosarcomas, both alveolar and embryonal, demonstrated uniform desmin, CD56, and cytoplasmic WT1 immunostaining. Desmoplastic small round cell tumors showed positive cytokeratin staining, with half having "dot-like" cytoplasmic desmin and WT1 positivity; some showed focal positivity for NB84, CD99, and Bcl-2. The "undifferentiated" sarcomas showed the widest range of staining, with no marker staining all cases. Neuroblastomas exhibited uniform strong staining for CD56 and NB84 and marked cytoplasmic Bcl-2 positivity, and some cases showed cytoplasmic WT1 expression. Blastematous Wilms' tumors showed uniform strong membranous staining for CD56, uniform cytoplasmic staining for Bcl-2, and nuclear expression of WT1. Embryonal pediatric malignancies can demonstrate apparently nonspecific expression patterns for several antigens, which may reflect developmental immaturity rather than specific differentiation pathways.     

Mixed tumors of the vagina: an immunohistochemical study of 13 cases with emphasis on the cell of origin and potential aid in differential diagnosis.

Mixed tumors of the vagina (MTsV) are rare benign neoplasms characterized by an admixture of well-differentiated epithelial cells and stromal-type cells in various proportions. In contrast to mixed tumors in other anatomic sites, the histogenesis of the vaginal tumors is unclear. We studied the immunohistochemical profile of 13 examples to explore their histogenesis and determine whether their immunohistochemical profile might be useful in the differential diagnosis. The panel of antibodies used and the number of cases studied were: AE1/3 (12), cytokeratin 7 (CK7) (13), cytokeratin 20 (CK20) (13), epithelial membrane antigen (EMA) (13), muscle actin (MA) (12), desmin (11), h-Caldesmon (13), CD10 (13), CD34 (11), CD99 (8), and S-100 (7). Eight out of 12 tumors were positive for AE1/3, 7/13 for CK7, 2/13 for CK20, and 6/13 for EMA. MA was positive in 11/12 mixed tumors, desmin in 10/11 tumors and h-Caldesmon in 5/13. All tumors were extensively positive for CD10; CD34 was positive in 7/11; and none out of eight tumors showed membranous CD99 staining. Focal S-100 immunoreactivity was seen in 1/7 tumors. These results show that MTsV coexpress epithelial and mesenchymal markers. The expression of muscle actin (usually extensive), and focal desmin and h-Caldesmon positivity suggests the presence of a smooth muscle or myoepithelial component; however, the S-100 negativity and diffuse CD10 expression argue against it. Positivity for muscle markers does not help distinguish MTsV from smooth muscle or skeletal muscle tumors. The frequent expression of CD10 negates its use in the differential diagnosis with endometrial stromal tumors, and the CD10 and CD34 expression suggests that mixed tumors may arise from a primitive pluripotential cell. MTsV are positive for h-Caldesmon and CD10, two markers that have been used in gynecologic pathology primarily to aid in establishing the smooth muscle or endometrial stromal phenotype of a neoplasm.     

Variable antigen expression in hepatoblastomas.

Hepatoblastoma is a malignant tumor that typically presents as a mass in the liver of a child less than 5 years of age. The diagnosis is usually established by means of a needle core biopsy before the treatment is commenced. The pathologic diagnosis of hepatoblastoma relies on the microscopic identification of typical morphologic features, but these may not be present in a needle core biopsy, and in this setting immunohistochemical staining has an important role in the exclusion of other childhood malignancies. We have studied 12 needle core biopsies from cases of hepatoblastoma, all of which had the diagnosis confirmed by subsequent resection of the tumor, to determine if these tumors show a diagnostic phenotype. The needle biopsies were immunostained with a standard panel of antibodies normally used in the characterization of childhood small round blue cell tumors, with the addition of antibodies directed against alpha-fetoprotein and alpha-1-antitrypsin. Our results indicate that the majority of hepatoblastomas expressed cytokeratins (10/12) and that alpha-1-antitrypsin and alpha-fetoprotein staining were positive in approximately half the cases (5/12 and 7/12, respectively). We also observed frequent expression of antigens normally expressed on other childhood tumors. A significant number of hepatoblastomas (8/12) expressed MIC-2 (CD99) an antigen normally associated with primitive neuroectodermal tumor, 4 cases showed positive staining with the neural-associated antigen NCAM (CD56), and 3 were positive with the neuroblastoma marker NB84. Occasional cases showed expression of the muscle marker desmin (2/12) and 2 cases stained with BCL2. Vimentin expression was seen in 1 case, and a single case also expressed the neural markers PGP9.5 and neurone-specific enolase. In all cases, the tumor cells were negative with CD45, WT1, and S-100. These findings indicate that the primitive cells in hepatoblastoma have a variable immunophenotype and can express antigens normally seen in other childhood malignancies. In the clinical setting of the differential diagnosis of childhood abdominal mass, hepatoblastoma shows no distinct immunohistochemical profile, and the diagnosis requires a combination of the clinical, imaging, and pathologic findings.     

Cell biology and matrix biochemistry of chondromyxoid fibroma

We studied matrix composition and gene expression pattern in chondromyxoid fibromas on the protein and the messenger RNA levels. We could clearly identify focal chondrocytic differentiation within chondromyxoid fibroma by the expression and deposition of type II collagen, which is a marker of chondrocytic cell differentiation. We also were able to show expression of collagen types I, III, and VI in the neoplasm. The major tumor portion was, however, characterized by the presence of hydrated proteoglycans and only minor amounts of collagens, a matrix composition responsible for the myxoid matrix appearance of most parts of these neoplasms. By analyzing cytoprotein expression, we found S-100 protein restricted to cells of the chondroid areas, suggesting S-100 protein staining to be of little help as a positive diagnostic marker for chondromyxoid fibroma. Our data show a specific matrix composition of chondromyxoid fibroma, not previously found in other mesenchymal neoplasms, including chondroblastoma, osteochondroma, enchondroma, and chondrosarcoma. This justifies chondromyxoid fibroma as a specific neoplastic entity, both clinically and biologically.     

Discovered on gastrointestinal stromal tumour 1 (DOG1): a useful immunohistochemical marker for diagnosing chondroblastoma

Akpalo H, Lange C & Zustin J
(2012) Histopathology  60, 1099–1106 Discovered on gastrointestinal stromal tumour 1 (DOG1): a useful immunohistochemical marker for diagnosing chondroblastoma Aims: Cellular areas of chondroblastoma are composed of polygonal chondroblasts with indented nuclei and scattered osteoclast‐type multinucleated cells. To learn more about the phenotype of chondroblasts, we investigated the expression of several established immunohistochemical markers in chondroblastomas. Methods and results: Nine chondroblastomas were analysed using immunohistochemical antibodies [CD34, α‐smooth muscle actin (α‐SMA), DOG1, CD117, AE1/AE3 and CD163]. Ten chondromyxoid fibromas, seven giant cell tumours of bone and four foetal proximal femurs were also analysed. The cellular areas of each chondroblastoma contained nests of DOG1⁺αSMA⁺ CD117^? CD34^? chondroblasts, a phenotype that was not detected in chondromyxoid fibroma cases or in giant cell tumours. Although AE1/AE3 was expressed in all chondroblastomas, the staining intensity and proportion of the positive cells varied widely. Intra‐lesional CD163⁺ macrophages were detected in all cases of chondroblastoma, chondromyxoid fibroma and giant cell tumours. Conclusions: Our results demonstrated nests of membranous DOG1⁺ chondroblasts located within cellular portions of chondroblastoma containing diffuse heterogeneous infiltrates of mostly DOG1^? chondroblasts, CD163⁺ macrophages and multinucleated osteoclastic giant cells. Thus, chondroblastoma can be added to the tumours that are usually positive for DOG1, alongside gastrointestinal stromal tumour (GIST), rare solid‐pseudopapillary neoplasms of the pancreas and exceptional mesenchymal tumours including uterine type retroperitoneal leiomyoma, peritoneal leiomyomatosis and synovial sarcoma.     

Gastrointestinal stromal tumors (GISTs): CD117, DOG-1 and PKCθ expression. Is there any advantage in using several markers?

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. Expression of CD117, DOG1 and PKCθ was investigated immunohistochemically in a series of 99 paraffin-embedded GISTs in order to determine the sensitivity and diagnostic value of these markers. KIT exons 9, 11, 13 and 17 and PDGFRA exons 12 and 18 were amplified by PCR and sequenced. A total of 94/99 (94%) GISTs stained positive for CD117, 81/99 (82%) for PKCθ and 90/99 (91%) for DOG-1. A significant correlation was noted between CD117 and DOG-1 expression (p=0.0001). All three markers were expressed in 74% (73/99) of GISTs. Of the five CD117-negative cases, two were PKCθ-negative/DOG1-negative and had mutations in KIT exon 11. Two were PKCθ-positive/DOG1-positive and had mutations in PDGFRA (one each in exons 12 and 18), and one was DOG1-negative/PKCθ-positive, with a PDGFRA exon 18 mutation. The most sensitive marker was CD117, followed by DOG-1 and PKCθ. Although PKCθ was less sensitive, and its staining is more challenging and difficult to interpret, the use of this marker is highly recommended, particularly in CD117-negative/DOG-1-negative GISTs.