Cellular Fibrous Histiocytoma Research Articles

Giant pretibial cellular fibrous histiocytoma colliding with an epidermal cyst

Histiocytomas are common benign tumors of the skin. In contrast, giant histiocytomas are a rarity. We report a 43-year-old male patient, who presented with a 7 × 6 cm large firm tumor on his left lower leg. This was a long-standing lesion, but within the last three months, the tumor developed an exophytic nodule. A skin biopsy revealed an atypical spindle-cell tumor. We decided to perform a complete excision with a safety margin. Complete histopathological analysis confirmed the diagnosis of a collision tumor composed of a cellular fibrous histiocytoma and an epidermal cyst. The resulting defect was temporarily closed by vacuum-assisted closure before eventually a meshed split skin graft was transplanted. Proliferating fibrohistiocytic lesions should be surgically removed, and a careful histopathologic analysis is necessary to avoid delayed diagnosis of possible malignant lesions.

Epithelioid fibrous histiocytoma: three diagnostically challenging cases with novel ALK gene fusions, unusual storiform growth pattern, and a prominent spindled morphology.

Epithelioid fibrous histiocytoma (EFH) is a distinctive cutaneous neoplasm with a relatively variable morphological appearance. Recently, it has been shown that this tumor is molecularly characterized by ALK gene fusions. We report three EFHs with unusual histological presentation represented by a prominent/predominant spindle cell proliferation arranged in a variably storiform/whirling architectural pattern with or without stromal sclerosis. One of the cases closely resembled cellular fibrous histiocytoma. All three cases were immunohistochemically ALK-positive and were analyzed for ALK gene rearrangements using a next-generation sequencing-based assay (FusionPlex Sarcoma Kit, ArcherDx). Three novel fusions, namely AP3D1::ALK, COL1A::ALK, and LRRFIP2::ALK, were detected and further confirmed by FISH in all 3 cases and RT-PCR in 1 case. All patients were elderly (62-63years) and presented with a solitary polypoid lesion on the extremities. The awareness of these morphological variants is important since it entertains a wide and slightly different differential diagnosis than conventional EFH. We also presented evidence that a clear separation of EFH from BFH in all cases may not be as straightforward as previously thought. The consistent ALK immunoexpression and the continually expanding scale of ALK gene rearrangements provide a useful tool to distinguish EFH from its histologic mimics.

Cellular benign fibrous histiocytoma in an 11-month-old child.

Fibrous histiocytoma of the skin is considered a benign tumor; however, in some cases it is characterized by local recurrences and sometimes metastases (2); most of these cases belong to the cellular variant. Cellular benign fibrous histiocytoma (CFH) usually appears in young adults, prefers the male sex and its most frequent location is the upper limb / shoulder girdle; its size usually does not exceed 2.5 cm; in 26% of cases CFH relapses locally (1). From a histological point of view one third of cases extends to the subcutaneous fat tissue and 12% of cases have foci of cellular necrosis; cell polymorphism is always present and the mitotic index is never high. The negativity of CD34 allows to exclude dermatofibrosarcoma protuberans, with which this tumor has sometimes been confused (1). The current case of CFH is therefore characterized by the early onset – third month – and by the considerable extension.

PSEUDOSARCOMATOUS MYOFIBROBLASTIC LESIONS OF THE ORAL CAVITY

Myofibroblastic lesions of the oral cavity can vary greatly in their histologic appearance. Occasionally, lesions of myofibroblastic origin can exhibit aggressive histologic features such as brisk mitotic activity and extension into underlying skeletal muscle and adipose tissue. Such cases can present a diagnostic challenge and can be aided by immunohistochemical (IHC) studies along with key morphological features to arrive at the appropriate diagnosis. The following is a discussion of two such cases. The first example presented as an exophytic lesion of the left dorsum of the tongue in a 73-year-old male. Histologically, the lesion was highly cellular, exhibited a moderate mitotic rate and showed extension into underlying skeletal muscle and adipose tissue. The lesional cells were focally positive for smooth muscle actin (SMA) and desmin by IHC, showed retention staining for retinoblastoma 1 (RB1) and was negative for CD34. The lesion was classified as a cellular fibrous histiocytoma. The second case also occurred on the tongue and presented in a 23-year-old female patient. Microscopically, this lesion was composed of mitotically active myofibroblasts set in a myxoinflammatory stroma. By IHC the lesion was positive for ALK and SMA but negative for keratin markers. Based on the histologic and IHC findings the lesion was diagnosed as a pseudosarcomatous myofibroblastic proliferation. Reactive and benign neoplastic myofibroblastic lesions can exhibit features suggesting malignancy, which can lead to misdiagnosis and mismanagement. The aim of this study was to examine and provide a discussion of two such cases and to illustrate how the IHC profile along with the overall morphology of the lesion can lead to the appropriate diagnosis of these challenging cases.

Metastatic cellular fibrous histiocytoma

Fibrous histiocytoma is a common benign cutaneous tumor. Although most cases of fibrous histiocytoma pursue an indolent course, rare cases have been reported that show aggressive courses with metastases and fatality despite a benign pathology. Here, we present a 30-year-old man with metastatic cellular fibrous histiocytoma. To our knowledge, this is the first case report of such a disease entity in Taiwan.

Giant Atypical Ulcerated and Polypoid Deep Cellular Fibrous Histiocytoma With a Novel Complex Karyotype

Giant Atypical Ulcerated and Polypoid Deep Cellular Fibrous Histiocytoma With a Novel Complex Karyotype

Diagnostic pitfalls in soft tissue pathology

This lecture will focus on commonly encountered traps which may mislead pathologists when interpreting soft tissue lesions. These have been selected to reflect issues raised most frequently in consultation cases, based mainly on either over- or under-interpretation of morphological or immunohistochemical findings. Key themes include awareness of natural history (e.g., an inappropriate clinical context for a given diagnosis), benign lesions often mistaken for malignant (e.g., cellular benign fibrous histiocytoma, cellular schwannoma or lipomas with microscopic fat necrosis), malignant lesions easily mistaken as benign (e.g., low-grade fibromyxoid sarcoma and solitary fibrous tumour) and misinterpretation of immunohistochemical stains (e.g., use of needlessly broad panels, excessive antigen retrieval, mistaken assumptions regarding specificity and speculative but unvalidated use of biomarkers to distinguish benign from malignant).

Cellular variant of benign fibrous histiocytoma: A case report

Benign fibrous histiocytoma or dermatofibroma is on e of the most common types of benign, cutaneous, so ft tissue tumors, most often found in the middle-aged adults. The diagnosis of dermatofibroma/benign fibrous his tiocytoma is usually straightforward if the typical morphologica l features are present. However, some diagnostic difficulties may arise when one is dealing with some unusual morphological variants. Among these variants, cellular fib rous histiocytoma (CFH) may represent a diagnostic chall enge because there is a risk of it being confused w ith other benign or malignant dermal tumours. Careful histopathological examination with the clear knowledge of this variant is important to avoid a misdiagnosis of a possibly more aggressive tumor. We are hereby briefly highli ghting the intriguing nature of cellular benign fibrous histio cytoma with which we have encountered.

Fatal Case of Metastatic Cellular Fibrous Histiocytoma

Cellular fibrous histiocytoma was first described in 1994 as a distinct variant of fibrous histiocytoma. Since then, at least 21 cases of cellular fibrous histiocytomas metastasizing to regional lymph nodes and/or lungs have been described, though not all fatal. We report the case of a 68-year-old male patient who presented with a large ulcerated skin tumor on the left thigh. The lesion was urgently excised. Histopathological examination led to the diagnosis of cellular fibrous histiocytoma. Nine months later, the patient presented with progressive dyspnea. A thoracoabdominal computed tomography revealed diffusely spread nodular lung lesions. A lung biopsy confirmed them to be metastases of the cellular fibrous histiocytoma. The condition of the patient quickly deteriorated, and he deceased 2 months later. Given the possible aggressive nature of cellular type of fibrous histiocytoma, we advice complete excision and clinical follow-up. Chest x-rays and ultrasound examination of regional lymph nodes should be performed in atypical lesions.

DNA copy number changes in tumors within the spectrum of cellular, atypical, and metastasizing fibrous histiocytoma

Cutaneous fibrous histiocytoma (FH) is a common mesenchymal neoplasm. Metastasis is rare, disproportionately occurring among the aneurysmal, cellular, atypical, and deep variants. We determined whether DNA copy number changes occurred in atypical FH (AFH), and whether they were similar to those in metastasizing FH (MetFH) and benign cellular FH (CFH). Five primary tumors of MetFH were evaluated by array-based comparative genomic hybridization analysis, with tissue from local recurrences and lung metastases in 2 and 2 patients, respectively. Seven indolent AFH and 5 CFH were identified for comparison. Substantial differences between the groups were found both in the frequency of chromosomal aberrations (higher among MetFH and absent or solitary in CFH) and array-based comparative genomic hybridization profiles (frequent gains of 7 and 8q and losses of Xq in MetFH; recurrent losses of chromosomes 9 and 22 in AFH; isolated loss of 5q and gain in chromosome 20 in 2 CFH). Fatal MetFH cases (2 of 5 cases) exhibited the highest rate of chromosomal aberrations. This study included a small sample size with a short-term follow-up. Benign CFH, indolent AFH, and MetFH represent distinct biological entities within the spectrum of FH; array-based comparative genomic hybridization may be a tool in recognizing FH cases with metastatic potential and increasingly aggressive behavior.

Cellular fibrous histiocytoma: a clinicopathologic analysis of 27 cases

To study the clinicopathologic characteristics of cellular fibrous histiocytoma (CFH) with emphasis on diagnosis and differential diagnosis. Clinical and pathologic features were reviewed in 27 cases of CFH (encountered during the period from 2008 to 2012) along with outcome analysis. Immunophenotyping was performed with EnVision method. The patients included 13 males and 14 females. The age at presentation ranged from 15 to 61 years (mean, 34 years; median, 32 years). The tumor occurred in the extremities (n = 14), head and neck (n = 7), and trunk (n = 6). Histologically, the tumors were located in the dermis. Some cases showed wedge like extension into the subcutaneous adipose tissue. On high power, they consisted of dense fibroblasts and myofibroblasts. Other cell components such as psammoma-like histiocytes, hemosiderin-containing macrophages or touton-type giant cells were rare. The spindled tumor cells were arranged mostly in intersecting fascicles. Focal storiform architecture was not uncommon. In addition, a few cases showed prominent hemangiopericytoma-like pattern. There was no prominent cellular atypia but increased mitotic figures were not difficult to find. Two cases exhibited necrosis. By immunohistochemistry, the tumor cells showed variable expression of alpha smooth muscle actin. CD34 positive cells were present in some cases, but were distributed mostly in the periphery or bottom of the lesions. They were all negative for desmin, h-caldesmon, S-100 protein and cytokeratin. Follow-up in 19 cases revealed local recurrences in 5 cases and bilateral pulmonary metastases in 1 case after repeated recurrences. CFH is a cellular form of benign fibrous histiocytoma which has a risk for local recurrence after incomplete excision. Distant metastasis can occur in rare examples. However, there were no morphological parameters predicting the risk of recurrence or metastasis. Increased awareness of the clinocopathological features and immunophenotypes of CFH is helpful in avoiding misdiagnosing the disease as malignant tumors, especially dermatofibrosarcoma protuberans.

English

English

Desmin and CD34 positivity in cellular fibrous histiocytoma: an immunohistochemical analysis of 100 cases

Cellular benign fibrous histiocytoma (CBFH) represents a morphologic variant of cutaneous fibrous histiocytoma (FH). Because of its relative monomorphism and frequent fascicularity, CBFH can easily be mistaken for a malignancy. In fact, CD34, often used to distinguish CBFH from dermatofibrosarcoma protuberans (DFSP), can also be positive. To add to the confusion, desmin positivity may also be observed in a subset of CBFH. Desmin and CD34 expression often cause interpretative difficulty which may lead to misdiagnosis. Our aim was to examine the incidence of desmin and CD34 expression in CBFH. One hundred consecutive cases of morphologically typical CBFH were retrieved from consultation files. Clinicopathologic and immunohistochemical features were evaluated. SMA positivity was found in tumor cells in 93 of 100 cases (93%). Desmin positivity was found in 32 of 100 cases (32%). CD34 was positive in 6 of 100 cases (6%). There was no evident correlation between immunophenotype and anatomic site or other clinical variables. Frequent desmin (32%) and occasional CD34 (6%) expression are encountered in CBFH. Desmin positivity can be explained on the basis of myofibroblastic differentiation. The occasional CD34 positivity in a subset of CBFH should not be a deterrent from making the correct pathologic diagnosis, based on characteristic morphologic features.

Differential gene expression profiles of neurothekeomas and nerve sheath myxomas by microarray analysis

Neurothekeomas and dermal nerve sheath myxomas have previously been considered related cutaneous neoplasms of peripheral nerve sheath origin based on light microscopic similarities. However, recent immunohistochemical and ultrastructural data indicate nerve sheath myxomas exhibit true nerve sheath differentiation, whereas no such compelling evidence exists for neurothekeomas. Although neurothekeomas lack a specific immunohistochemical profile, similar antigen expression and histopathologic patterns suggest neurothekeomas may be categorized as fibrohistiocytic tumors. To date, no known molecular studies have examined the histogenetic relationship of these tumors. We report the first microarray-based gene expression profile study of these entities on formalin-fixed paraffin-embedded tissues. Cases of dermal schwannomas, dermal nerve sheath myxomas, myxoid/mixed/cellular neurothekeomas, and cellular fibrous histiocytomas diagnosed in the past 3 years were identified in our database. Archival formalin-fixed paraffin-embedded tissue from 28 patients was selected for microarray analysis (seven schwannomas, five nerve sheath myxomas, nine myxoid/mixed/cellular neurothekeomas and seven cellular fibrous histiocytomas). Following tumor RNA isolation, amplification and labeling using commercially available kits, labeled targets were hybridized to the Affymetrix GeneChip Human Genome U133 Plus 2.0 Array (Santa Clara, CA, USA). Acquisition of array images and data analyses was performed using appropriate software. Hierarchical clustering and principal component analysis demonstrated discrete groups, which correlated with histopathologically identified diagnoses. Dermal nerve sheath myxomas demonstrate very similar molecular genetic signatures to dermal schwannomas, whereas neurothekeomas of all subtypes more closely resemble cellular fibrous histiocytomas. We are the first to report distinct gene expression profiles for nerve sheath myxomas and neurothekeomas, which further substantiates the argument that these are separate entities. Our molecular data confirms that dermal nerve sheath myxomas are of peripheral nerve sheath origin, and suggests that neurothekeomas may actually be a variant of fibrous histiocytomas.

Adult-type Fibrosarcoma: A Reevaluation of 163 Putative Cases Diagnosed at a Single Institution Over a 48-year Period

Adult-type fibrosarcoma (FS) was once considered the most common adult sarcoma, but is now considered a diagnosis of exclusion. No recent series has critically reevaluated putative FSs to estimate their true incidence. One hundred ninety-five cases diagnosed as adult FS in somatic soft tissue were retrieved from our institutional archives for the period 1960 to 2008. Thirty-two cases with insufficient material were excluded. On the basis the morphology of the final 163 cases, immunohistochemical studies (IHC) was conducted using some combination of: wide-spectrum cytokeratin (CK), EMA, high molecular weight CK, S100, Melan A, HMB-45, CD34, TLE1, CD31, HHV8, smooth muscle actin, desmin, ALK1, CD99, Myo-D1, myogenin, c-kit, INI1, CD21, p63, calretinin, WT1, and TTF1. Fluorescence in situ hybridization analysis for SYT gene rearrangement was done in 6 putative CK-negative synovial sarcomas (SS). Revised diagnoses were based on clinical, morphologic, IHC, and molecular findings. The original group of putative FS occurred in 84 males and 79 females (median 52.5 y, range 2 to 99 y), and involved various anatomic sites. Only 26 cases met WHO criteria for FS, including 2 postradiation FS. These occurred in 16 males and 10 females (median 50 y, range 6 to 74 y), and involved the lower extremities (12 cases), head/ neck (5 cases), trunk (4 cases), upper extremities (3 case), and mediastinum/abdomen (2 cases). Clinical follow-up information was available for 24 of 26 (92%) cases, with a median of 5 years follow-up (range <1 to 35 y). Twelve patients (50%) died of locally aggressive and/or metastatic disease (median follow-up 1-year; range <1 to 8 y), 6 patients (25%) were alive without disease (median follow-up 11.5 y; range 2.5 to 35 y), and 6 patients (25%) died of other causes (median follow-up 10 y; range 9 to 18 y) (). Fluorescence in situ hybridization analysis was positive for SYT gene rearrangement in all cases tested. Non-FS (137 cases) were reclassified as: undifferentiated pleomorphic sarcoma (32 cases), SS (21 cases), solitary fibrous tumor (14 cases), myxofibrosarcoma (11 cases), malignant peripheral nerve sheath tumor (8 cases), FS dermatofibrosarcoma protuberans, and desmoplastic melanoma (4 cases each), low-grade fibromyxoid sarcoma, sarcomatoid carcinoma, desmoid-type fibromatosis, rhabdomyosarcoma, myofibroblastic sarcoma, spindle-cell liposarcoma (3 cases each), sclerosing epithelioid FS, fibroma-like epithelioid sarcoma, leiomyosarcoma, cellular fibrous histiocytoma (2 cases each), and others (17 cases). Using modern diagnostic criteria with ancillary IHC and molecular genetics, we have been able to reclassify 84% of putative FS. Exclusive of undifferentiated pleomorphic sarcoma, the distinction of which from FS is subjective, 64% of putative FS were reclassified, most commonly as monophasic SS and solitary fibrous tumor. We conclude that true FS is exceedingly rare, accounting for <1% of approximately 10,000 adult soft tissue sarcomas seen at our institution during this time period, and should be diagnosed with great caution.

D2-40, a novel immunohistochemical marker in differentiating dermatofibroma from dermatofibrosarcoma protuberans

The distinction between dermatofibroma, particularly cellular variant, and dermatofibrosarcoma protuberans in excisional biopsies is usually straightforward. However, a separation between the two may be sometimes challenging, especially in superficial biopsies. Although factor XIIIa and CD34 immunostains are useful in differentiating dermatofibroma and dermatofibrosarcoma protuberans in most instances, focal CD34 positivity may be seen in cellular fibrous histiocytoma. Some cases reveal overlapping immunostain results. D2-40 identifies a 40-kDa O-linked sialoglycoprotein present on a variety of tissues including testicular germ cell tumors as well as lymphatic endothelium. In this study, we investigated the utility of D2-40 in separating dermatofibroma from dermatofibrosarcoma protuberans and compared the results with other commonly used immunostains. Fifty-six cases of dermatofibroma (including six cellular variant) and 29 cases of dermatofibrosarcoma protuberans were retrieved from the archives of Department of Anatomic Pathology at Sunnybrook Health Sciences Center in University of Toronto. We applied factor XIIIa, CD34, and monoclonal mouse anti-D2-40 immunostains to formalin-fixed, paraffin-embedded tissue sections. All 56 (100%) cases of dermatofibroma demonstrated strong and diffuse immunoreactivity to D2-40 in the spindle cells and stroma. Similarly, factor XIIIa showed strong and diffuse positivity in the spindle cells. Nearly all dermatofibromas were negative for CD34 except one case revealing focal positivity. None of dermatofibrosarcoma protuberans cases were labeled by D2-40, although four cases showed weak and patchy background staining in contrary to diffuse, strong, and crisp staining seen in dermatofibromas. Our results indicate that D2-40 seems to be a sensitive immunohistochemical marker for dermatofibromas, including cellular variant. Focal and faint D2-40 staining may be seen in the stroma of dermatofibrosarcoma protuberans. Our findings suggest that D2-40 can be used as a complementary immunostain to factor XIIIa and CD34 in problematic and challenging cases on superficial biopsies.

富細胞性皮膚線維腫の1例

47歳男性。7ヵ月前より右肩部に赤黒い結節が出現，3ヵ月から急速に増大し，出血を認めるようになった。初診時右肩に33×26×28mmの潰瘍化した半球状の紅色腫瘤を認めた。下床との可動性は良好であった。造影MRIでは内部構造が均一で境界明瞭な結節であり，筋や骨の浸潤は認められなかった。線維組織球系の肉腫を疑い，全身麻酔下に全摘切除を行った。病理組織学的に主に真皮に軽度の核異型を伴う紡錘形細胞が花むしろ状に密に増殖しており，富細胞性皮膚線維腫と診断した。

Cutaneous fibrohistiocytic tumours – an update

The term 'fibrohistiocytic' tumour is a descriptive designation without histogenetic connotation for a group of heterogeneous lesions that share morphological features of histiocytes and fibroblasts on light microscopy. However, over the years it has become apparent that many so-called 'fibrohistiocytic' tumours are largely composed of relatively undifferentiated mesenchymal cells, but can also show areas of myofibroblastic differentiation. This review focuses on the clinical and histological features as well as differential diagnosis of so-called fibrohistiocytic tumours. Special emphasis is given to more recently described histological variants of fibrous histiocytoma, e.g. cellular, epithelioid, aneurysmal and atypical fibrous histiocytoma, to angiomatous and plexiform fibrous histocytoma (plexiform fibrohistiocytic tumour), lesions that are not true variants of fibrous histiocytomas but have erroneously been designated such, and to atypical fibroxanthoma. The literature on metastasizing fibrous histiocytoma is also reviewed.

Diagnostic value of CD163 in cutaneous spindle cell lesions

The histologic diagnosis of atypical fibroxanthoma (AFX) can sometimes be challenging. No specific marker exists to confirm the diagnosis other than excluding other entities. CD163 has been shown to have great specificity for tumors of monocyte/histiocyte lineage. In this study, we evaluated the diagnostic utility of CD163 in diagnosing AFX and in identifying skin lesions with histiocytic/dendritic derivation. A total of 157 cases, including 14 AFXs, 5 spindle cell squamous cell carcinomas (SCCs), and 7 spindle cell/desmoplastic melanomas, along with other cutaneous spindle cell and histiocytic/fibrohistiocytic lesions, were stained with CD163. CD163 was expressed in 11 of 14 (79%) AFXs, with moderate to strong intensity. No staining was observed in cases of spindle cell SCC (0/5) and dermatofibrosarcoma protuberans (0/10). Rare spindle cell/desmoplastic melanomas (2/7) and cutaneous leiomyosarcomas (1/5) demonstrated positive staining. CD163 reactivity was seen in 24 of 29 of benign fibrous histiocytomas (BFHs), including 8 of 8 cellular fibrous histiocytomas and 6 of 9 epithelioid cell histiocytomas. The majority of cutaneous histiocytic lesions, including juvenile xanthogranuloma, Langerhans cell histiocytosis and Rosai-Dorfman disease, were positive for CD163. CD163 is a useful adjunct in distinguishing AFX from other malignant cutaneous spindle cell tumors and offers improved specificity in identifying cutaneous histiocytic/dendritic lesions.

Expression of CD163 in dermatofibroma, cellular fibrous histiocytoma, and dermatofibrosarcoma protuberans: comparison with CD68, CD34, and Factor XIIIa

Expression of CD163 in dermatofibroma, cellular fibrous histiocytoma, and dermatofibrosarcoma protuberans: comparison with CD68, CD34, and Factor XIIIa