Pleomorphic hyalinizing angiectatic tumor

Authors present an additional case report of pleomorphic hyalinizing angiectatic tumor (PHAT), only recently recognized entity amongst the soft tissue tumors. 63-year-old man underwent surgery for subcutaneous tumor growing on the forearm. Grossly, ovoid well demarcated tumor 4.0 x 3.5 x 2.5 cm was removed. Histologically, hypovascular areas of spindle-cells arranged in sheets and fascicles resembling spindle-cell sarcoma and areas rich on ectatic vessels with fibrin deposits or thickened hyalinized walls were present. Some cells contained intranuclear cytoplasmatic inclusions, lobulated nuclei with or without prominent nucleoli or multiple nuclei. Mitoses were less than 1 per 30 HPF, Ki-67 nuclear positivity was observed in 2.6% of tumor cells. Immunohistochemically, cells were positive with vimentin, but negative for CD34, S100, desmin, smooth-muscle actin, EMA, VWF, CD99, bcl-2 and cytokeratins. The patient did well, without recurrent tumor after 13 months follow-up. Spectrum of tumors including solitary fibrous tumor, giant-cell angiofibroma, neurilemmoma, malignant fibrous histiocytoma and acral myxoinflammatory tumor with atypical bizarre giant cells is discussed in differential diagnosis.     

Pleomorphic hyalinizing angiectatic tumor of soft parts

A case of recently descrlbed pleomorphic hyaliniring anglectatic tumor (PHAT) of soft parts Is reported. The subcutaneous solid tumor arising In the axils of a 58-year-old man was histologically characterized by sheets of mitotic ally Inactive oval and pleomorphic cells, Itranuclear cytoplasmic Inclusions, and clusters of ectatic vessels with perivascular hyalinization. Mono- and multinucleated giant cells were also present. A hemanglopericytoma-like pattern of vascularity, pseudovascular spaces, stromal collagen with degenerative changes, and Immunoreactivity for CD34 were observed. Since these features were very similar to those of solitary fibrous tumors of various sites and newly categorized giant cell angiofibroma, it Is considered that PHAT, solitary fibrous tumor, and giant cell angiofibroma may be In the same family of tumor. The tumor was diploid with a low S-phase fraction. The patient was well with no evidence of disease for 23 months.     

软组织多形性透明变性血管扩张性肿瘤

目的：探讨软组织多开矿性透明变性血管扩张性肿瘤的临床病理学特点。方法：对２例软组织多形性透明变性血管扩张性肿瘤进行光镜观察和免疫组化检测。结果：１例为５８岁女性,表现为颈部皮下缓慢性生长的肿块;另１例为３１岁男性,表现为右后腹膜内肿块。眼观,肿瘤境界均较清楚,镜检,显示以下三个特征性的形态学改变：（１）呈簇性分布扩张性的薄壁血管;（２）分布于扩张血管之间的多形性瘤细胞;（３）血管壁、血管周围及瘤细     

Pleomorphic hyalinizing angiectatic tumor: cytomorphologic features on fine-needle aspiration

Pleomorphic hyalinizing angiectatic tumor (PHAT) is a rare low-grade neoplasm occurring predominantly in the subcutaneous tissue of the lower extremity, which is characterized histologically by intermixed bland spindle cells and larger pleomorphic cells, ectatic blood vessels with fibrin, and prominent hyalinization. Here we describe the cytologic features of PHAT seen on fine-needle aspiration of a right calf mass in a 46-year-old man. The smears were cellular, composed predominantly of bland spindle cells dispersed singly as well as in tissue fragments and characterized by open chromatin and small nucleoli. A second population of pleomorphic spindle cells with coarse chromatin, prominent nucleoli, and occasional intranuclear pseudoinclusions was also present. Many of the pleomorphic cells surrounded hyalizined vessels. No mitotic figures were identified. The cytologic diagnosis was a "spindle cell lesion, NOS" with the differential diagnosis including benign lesions and low-grade neoplasms, including PHAT and schwannoma.     

Pleomorphic hyalinizing angiectatic tumor with a sarcomatous component recurring as high-grade myxofibrosarcoma

Pleomorphic hyalinizing angiectatic tumor (PHAT) of the soft tissue is a rare distinctive tumor listed as a benign neoplasm in the new World Health Organization classification. It may recur and most reported recurrent tumors retained the typical morphological appearance of PHAT; rare tumors recurred with the appearance of a sarcoma. Reported herein is an additional example of recurrent PHAT, but in contrast to the previously described cases the present tumor morphologically qualified as a sarcoma from the very beginning; it recurred as a high-grade myxofibrosarcoma. A 76-year-old woman presented with a solitary subcutaneous tumor in the axilla that was surgically removed. Seven months later, the patient experienced a local recurrence. Microscopically, the typical features of PHAT were identified in the initial lesion, namely hyalinized, fibrin-containing vessels and pleomorphic stromal cells; there were areas of hemorrhage and necrosis. Additionally, peripherally located areas of the tumor manifested highly pleomorphic cells with frequent atypical mitoses, producing a sarcomatous appearance. The mitotic index in the sarcomatous part was 1/10 high-power fields (HPF). Hyalinized, fibrin-containing vessels were absent in these sarcomatous areas, and the stroma was myxoid. The recurrent lesion was composed of large highly pleomorphic oval, round, spindled or bizarre cells with a high mitotic rate, ranging from 3/10 HPF to 7/10 HPF. The neoplastic cells were arranged haphazardly in a myxoid matrix. Hyalinized, fibrin-containing vessels typical for PHAT were absent. PHAT may be more aggressive than previously thought, and PHAT may encompass a morphological spectrum of the lesion ranging from benign to malignant.     

Pleomorphic hyalinizing angiectatic tumor of the male breast: a heretofore unreported occurrence

Pleomorphic hyalinizing angiectatic tumor (PHAT) is considered an unusual mesenchymal tumor of intermediate malignant potential that is distinguished by a prominent angiectatic vasculature with clusters of thin-walled, fibrin-lined vessels surrounded by sheets of spindled and pleomorphic cells. This lesion occurs mostly in the subcutaneous soft tissues of the lower extremities. In this paper, the authors report the first case of PHAT involving the breast parenchyma of a 75-year-old man. The patient was referred to the hospital with a history of a painless left breast mass that had been growing for several years. The lesion did not recur after surgery. The tumor exhibited histopathologic and immunohistochemical features identical to those of a PHAT of other sites. The purpose of this report is to add a rare tumor to the differential diagnosis of mammary spindle cell neoplasms.     

软组织多形性玻璃样变血管扩张性肿瘤的临床病理学观察

目的探讨软组织多形性玻璃样变血管扩张性肿瘤(pleomorphic hyalinizing angiectatic tumor of soft parts,PHAT)的临床病理特点。方法回顾性分析6例PHAT的临床资料、组织学形态和免疫组化标记,并复习相关文献。结果6例均发生于成年人,男性和女性各占3例,平均年龄为44岁。肿瘤分别位于下肢(3例)、颈部(2例)和腹膜后(1例)。临床上多表现为无痛性肿块,术前病程为3个月~38年。大体上,肿瘤境界清楚,结节状,平均直径为4.3 cm。切面呈灰白、灰红或灰褐色,部分病例可见出血性囊腔。镜下,肿瘤内含有成簇分布的薄壁扩张血管,血管壁附有一层厚的玻璃样变物质(纤维素和胶原纤维),可向血管周围间质内延伸,血管之间为片状分布的多形性瘤细胞,核大深染,核内可见假包涵体,但核分裂象罕见。部分区域内瘤细胞呈梭形,排列成条束状,类似神经鞘瘤。免疫组化标记显示,瘤细胞主要表达vimentin,部分病例还表达CD34和CD99,而S-100蛋白、α-SMA、bcl-2、EMA和CD68均为阴性。6例均经手术切除,随访8个月~13年,无1例复发。结论PHAT是一种具有低度恶性潜能的软组...     

Pleomorphic hyalinizing angiectatic tumor of soft parts: a case report and literature review

Pleomorphic hyalinizing angiectatic tumor (PHAT) is a rare, recently recognized neoplasm occurring predominantly in the subcutaneous tissue of the lower limbs of adults. We report a case of PHAT in an 83-year-old woman who presented with a 5.0 x 5.0 x 2.0 cm mass in the soft part of her left thigh. Histologically, the tumor was well circumscribed by a thin fibrous capsule and predominantly composed of fusiform cells with eosinophilic cytoplasm and round-to-oval or pleomorphic nuclei. The tumor cells resembled those of malignant fibrous histiocytoma, but differed from them by less prominent mitotic figures. Immunohistochemically, the tumor cells were diffusely and strongly positive for CD34; partially positive for vimentin and CD99 (MIC-2); and negative for epithelial and non-epithelial markers. Ultrastructurally, the tumor cells had pleomorphic cytoplasm and nucleus. Intermediate-sized cytoplasmic filaments were observed in a few tumor cells, but neurosecretory-type granule-like intracytoplasmic organelles were not seen. These findings suggest that this tumor is derived from stromal fibroblast, such as solitary fibrous tumors or giant cell angiofibroma.     

Pleomorphic hyalinizing angiectatic tumor of soft parts: ultrastructural analysis of a case with original features

Pleomorphic hyalinizing angiectatic tumor, a rare neoplasm of uncertain lineage resembling malignant fibrous histiocytoma and schwannoma, was first described in 1996 by M. E. F. Smith et al. (Am Surg Pathol. 20:21-29). To date, less than 100 cases have been reported in the international literature. It occurs in subcutaneous and intramuscular soft tissues of extremities or trunk in adults without sex predilection. All lesions are composed of sheets and fascicles of spindled and pleomorphic cells associated with clusters of thick-walled ectatic vessels surrounded by a perivascular hyaline material and inflammatory cells such as mast cells. About one-half of these neoplasms express CD34. No patient has developed metastases but occasional local recurrences are possible. This tumor of uncertain lineage is suggested to be an aggressive locally growing low-grade sarcoma. Only 3 cases were previously studied by electron microscopy and appeared to consist of primitive fibroblastic cells. The authors report histological and ultrastructural characteristics of a new case of PHAT excised from the right buttock of a 66-year-old man with the presence of ganglion-like cells, a feature that has not been previously reported, and unusual central ischemic necrosis. The features of this case are suggestive of a fibroblastic origin.     

Pleomorphic hyalinizing angiectatic tumor of soft parts: immunohistochemical study including the expression of vascular endothelial growth factor

We report morphologic, flow cytometric, and immunohistochemical findings in two cases of pleomorphic hyalinizing angiectatic tumor of soft parts. Both patients were middle-aged women with subcutaneous lesions located in the lower extremity. The tumors consisted of sheets of spindled and pleomorphic cells with frequent intranuclear pseudoinclusions associated with clusters of ectatic vessels surrounded by prominent perivascular hyaline material. Numerous, nonhyalinized vessels were also present, mostly in the peripheral areas of the lesions. Some of these vessels had their walls permeated by numerous small capillaries. Immunostaining for vascular endothelial growth factor (VEGF), a secreted protein that has been implicated in tumor-associated angiogenesis, demonstrated positive staining in both tumoral and endothelial cells. Tumor cells were also reactive to vimentin and CD34. Focal positivity for CD99 and factor XIIIa was also present. Flow cytometry yielded a diploid DNA histogram with S-phase fraction of 7%. Our findings corroborate those from previously reported cases. They further suggest that angiogenesis and the angiogenic factor VEGF may play a role in the development of this peculiar tumor.     

Pleomorphic hyalinizing angiectatic tumor of soft parts: Case Report with unusual ganglion-like cells and review of the literature

Pleomorphic hyalinizing angiectatic tumor (PHAT) is a recently described, non-metastasizing tumor of uncertain lineage. This tumor distributes equally between the genders and has a predilection for the subcutaneous soft tissue, particularly in lower extremity, other locations are rare. Based on the recent literature, PHAT is suspected to encompass the morphological spectrum with other tumors such as myxoinflammatory fibroblastic sarcoma (MIFS) and hemosiderotic fibrolipomatous tumor (HFLT), although cytogenetic data remain inconsistent. We report a case of PHAT that arose in the upper arm with unusual morphology which showed ganglion-like cells similar to Reed-Sternberg-like cells found in MIFS. The tumor had strong immunohistochemical expression of CD34, CD99, and was negative for S-100. The ganglion-like cells were positive for both CD34 and CD68 but negative for CD30. The translocation between chromosome 1 and 10, a frequent finding of MIFS and HFLT, was not identified by FISH excluding the possibility of hybrid PHAT and MIFS. We conclude FISH can be a potential useful tool to separate PHAT with atypical morphology from hybrid tumor in doubted cases. Due to the rarity of PHAT and lack of consistent pathogenetic signatures, more cases and further studies will be needed to elucidate the pathogenesis and nature of this tumor.     

Complex analysis of a recurrent pleomorphic hyalinizing angiectatic tumor of soft parts

Pleomorphic hyalinizing angiectatic tumor of soft parts is a recently recognized, low-grade mesenchymal neoplasm of uncertain lineage. It is characterized by clusters of ectatic, fibrin-lined, thin-walled vessels surrounded by pleomorphic but mitotically inert spindled cells with frequent intranuclear inclusions and a variable inflammatory component. Here, we report a case of recurrent pleomorphic hyalinizing angiectatic tumor in a 37-year-old white woman. Touch imprint cytologic analysis revealed oval and spindled cells with fine chromatin, occasional prominent intranuclear inclusions, and intracytoplasmic pigment. The histologic features of the cells constituting the bulk of tumor were those characteristic of a putative precursor lesion ("early pleomorphic hyalinizing angiectatic tumor") as well as another recently described entity known as hemosiderotic fibrohistiocytic lipomatous lesion. Cytogenetic analysis revealed 2 unbalanced translocations involving chromosomes 1 and 3 and chromosomes 1 and 10, with a karyotype of 45,XX,der(1)t(1;3)(p31;q12),-3,der(10)t(1;10)(p31;q25)[11]/46,XX[4], thus suggesting that this disease is neoplastic. The controversies in classification of these lesions are also discussed.     

Pleomorphic hyalinizing angiectatic tumor revisited: all tumors manifest typical morphologic features of myxoinflammatory fibroblastic sarcoma,further suggesting 2 morphologic variants of a single entity

We describe 9 cases of pleomorphic hyalinizing angiectatic tumor (PHAT). Recently described TGFBR3 and MGEA5 gene rearrangements in these tumors have confirmed the long-hypothesized link between PHAT and another soft tissue entity, the myxoinflammatory fibroblastic sarcoma (MIFS). Myxoinflammatory fibroblastic sarcoma and PHAT share the same translocation and in addition have a very similar clinical presentation. However, to our best knowledge, no study has ever addressed the striking morphologic similarities between MIFS and PHAT. Our findings based on histological criteria suggest that most, if not all, tumors diagnosed as PHAT might, in fact, represent examples of MIFS that, in addition to a conventional MIFS morphology, manifest aberrant angiectatic hyalinized vessels.     

A subcutaneous pleomorphic hyalinizing angiectatic tumor of soft parts of the right chest wall: report of a rare case

Pleomorphic hyalinizing angiectatic tumor of the soft parts is an extremely rare mesenchymal tumor consisting of spindled and pleomorphic tumor cells and clusters of ectatic, fibrin-lined vessels. It typically occurs in the subcutaneous tissues of the distal extremities, usually the ankles and feet. Here we present a case of pleomorphic hyalinizing angiectatic tumor of the soft parts of the right chest wall in a 51-year old female. The tumor was subcutaneous, nonencapsulated, and about 2.0 cm×1.0 cm. Microscopically, the tumor was composed of numerous ectatic, fibrin-filled, thin-walled blood vessels, surrounded by spindled or pleomorphic tumor cells arranged in sheet-like or fascicular architecture, or randomly. Mitotic activity of the tumor cells was low. Immunohistochemical analysis shows that the tumor cells were positive for CD34 and vimentin, but negative for CD31, CK, desmin, EMA, HMB45, Myo D1, P63 and S-100. Ki67 index was about 1%.     

A case of a pleomorphic hyalinizing angiectatic tumor of soft parts with intracytoplasmic hemosiderin pigment apparent upon fine‐needle aspiration cytology

Pleomorphic hyalinizing angiectatic tumors of soft parts are extremely rare low‐grade mesenchymal lesions that frequently occur subcutaneously, especially in the lower extremity. The tumor is histologically characterized by sheets of plump, spindled or rounded cells, and clusters of ectatic blood vessels. It also has a number of previously characterized cytological features such as pleomorphic cells, intranuclear pseudoinclusion, and intracytoplasmic hemosiderin pigments. However, intracytoplasmic hemosiderin has not been carefully evaluated in cytology specimens. Here, we report the case of a 56‐year‐old Japanese man with an encapsulated pleomorphic hyalinizing angiectatic tumor of soft parts that included fine and coarse hemosiderin‐laden tumor cells. The tumor was clinically followed up as a hematoma, but malignant tumors, including malignant melanoma, were suspected because aspiration cytology specimens contained pleomorphic cells with intracytoplasmic brown pigments. The tumor was closely associated with an intratumoral hematoma and a few microscopic satellite lesions. Pleomorphic hyalinizing angiectatic tumor of soft parts should be included in the differential cytological diagnosis of soft tissue tumors if the three cytological features described earlier are present. Enucleation therapy could facilitate local recurrence, as the tumor may have the potential to infiltrate surrounding soft tissue or form satellite lesions. Diagn. Cytopathol. 2015;43:407–411. © 2014 The Authors. Diagnostic Cytopathology Published by Wiley Periodicals, Inc.     

Hyaline matrix in hyalinizing trabecular tumor

Hyalinizing trabecular tumor (HTT) is a rare neoplasm which usually follows an indolent clinical course. The cytologic diagnosis of HTT can be challenging as these neoplasms share cytomorphological features with other thyroid neoplasms and paraganglioma. In fine‐needle aspiration (FNA) smears a diagnosis of papillary thyroid carcinoma (PTC) or suspicion of PTC is often made. Herein we report cytologic findings in two patients with HTT examined by FNA. The key to a correct diagnosis is the recognition of a hyaline and colloid/amyloid‐like material in the background of the smears. Immunocytochemical examination showing aberrant membranous and peripheral cytoplasmic staining for MIB‐1 can help in rendering a correct diagnosis. Diagn. Cytopathol. 2015;43:710–713. © 2014 Wiley Periodicals, Inc.     

Neuroendocrine differentiation in hyalinizing trabecular tumor of the thyroid

The presence of neuroendocrine cells is putative in thyroid hyalinizing trabecular tumor (HTT), although this entity requires a differential diagnosis from paraganglioma or medullary carcinoma of the thyroid, due to similarity of the growth pattern of the cells. Here, we present a case of HTT with a mixture of endocrine cells stained positive for somatostatin, chromogranin A and Grimelius silver impregnation. The histology and results of other immunostainings were consistent with the features typical for HTT. In the world literature to date, only two cases of HTT with endocrine cells, including the current case, have been reported. Nevertheless, the cases may indicate the diversified differentiation of cells in HTT and may, in part, account for the resemblance of HTT to paraganglioma and medullary carcinoma.     

Fine-needle aspiration cytology of pleomorphic hyalinized angiectatic tumor: A case report

Pleomorphic hyalinized angiectatic tumor (PHAT) of soft parts is a neoplasm characterized by spindle and pleomorphic cells associated with an angiectatic vasculature. We describe the cytological findings of a fine-needle aspiration biopsy (FNAB) from the right medial knee of a 45-yr-old woman. The aspirate material was entirely submitted in Cytolit solution. The specimen was moderately cellular and was comprised of spindle cells in a background of fibrinous material. The cells varied from small, bland spindle cells with a fine chromatin pattern and inconspicuous nucleoli to larger pleomorphic cells with coarser chromatin and occasional intranuclear inclusions. Most of the cells were arranged singly with sporadic small cluster formation with indistinct cell borders. Rare mononuclear inflammatory cells morphologically compatible with mast cells were identified. The differential diagnosis include solitary fibrous tumor (SFT) and ancient schwannoma, which also shows fibrous-like material and spindle cells that may have intranuclear inclusions.     

Cytological diagnostic challenge: two hyalinizing trabecular tumor case reports

Hyalinizing trabecular tumors (HTT) are very rare thyroid tumors whose diagnosis is difficult, particularly in cytology. They are frequently diagnosed as papillary carcinomas due to the cytological similarities between those two tumors (anisocariosis, intranuclear cytoplasmic inclusions, nuclear grooves and nuclear overlapping). Here, we report two HTT cases which were initially diagnosed as papillary carcinoma, on the preoperative cytology and for which the patients underwent total thyroidectomy with lymph node dissection. From these two cases and a literature review, we have searched for diagnostic criteria which could increase the sensitivity of HTT diagnosis in thin layer cytology. We have found that only the identification of the fibrillar and hyaline material within the cellular cluster of the HTT seems discriminating between both tumors, even though it is difficult to diagnose it is difficult to diagnose on thin layer cytology. One major help for the diagnosis would be the typical membranous and cytoplasmic MIB-1 immunostaining. However, no experiment has been undertaken with thin layer smears for HTT.     

Immunohistochemical and electron microscopy studies of a case of hyalinizing trabecular tumor of the thyroid gland,with special consideration of the hyalinizing mass associated with it

Hyalinizing trabecular tumor (HTT) of the thyroid gland is rare and benign, and it neither recurs nor metastasizes. In this lesion, tumor cells are arranged in trabeculae, in association with hyalinizing mass in the stroma. The origin and nature of the hyalinizing mass are still controversial. We report here a case of HTT with cytological, immunohistochemical, and ultrastructural findings, focused in particular on the hyalinizing mass. Cytologically, tumor cells exhibiting many intranuclear cytoplasmic inclusions and nuclear grooves were found in association with light green-positive, irregular, fluffy membranous structures on touch smear. Staining with antibody to collagen type IV was positive in these membranous structures. Histopathologically, tumor cells exhibited many intranuclear cytoplasmic inclusions, and were positive for staining with antibodies to S100 protein, neuron-specific enolase, thyroglobulin, and vimentin. The hyalinizing eosinophilic mass, which was positive for PAS reaction, and for staining by antibody to collagen type IV, gradually increased in the areas surrounding tumor cells. This mass then appeared to replace the tumor cells, and exhibited a peculiar filiform pattern. We demonstrated ultrastructurally that this pattern was composed of long, irregular, fine cytoplasmic processes of tumor cells and basal lamina-like substance in the hyalinizing mass. In fact, the homogeneous hyalinizing mass, similar to basal lamina-like substance, contained many degenerated cytoplasmic processes at the ultrastructural level. These results suggested that the key cytological finding in differentiating HTT from papillary carcinoma is the fluffy membranous structure, although nuclear pseudoinclusions are important as well. The filiform pattern noted at light microscopic level consisted of long cytoplasmic processes of tumor cells and hyalinized mass at the ultrastructural level.