Pleomorphic fibroma and dermal atypical lipomatous tumor: are they related?

Pleomorphic fibromas represent dome‐shaped or polypoid cutaneous lesions characterized by a paucicellular and densely fibrotic background punctuated by scattered atypical to pleomorphic spindle and multinucleated giant cells. Some of these tumors will have incorporated adipose tissue, although these adipocytic areas lack distinct cytologic atypia and may represent entrapped normal periadnexal or subcutaneous adipose tissue. Nonetheless, owing to the similarity of some of the morphologic features of pleomorphic fibroma with cutaneous atypical lipomatous tumor, diagnostic confusion can ensue. The potential diagnostic challenges are further highlighted by a recent report of a lesion with histopathologic features of both. In response, we studied the presence of 12q15/ MDM2 amplification by fluorescence in situ hybridization and MDM2 expression by immunohistochemistry in a series of 15 pleomorphic fibromas to investigate whether these two entities share a common pathogenic origin. One case of cutaneous atypical lipomatous tumor was used as positive control for 12q15 amplification. All 15 cases were negative for MDM2 by immunohistochemistry with no demonstrable 12q15/MDM2 amplification by fluorescence in situ hybridization. Therefore, these two entities are best regarded as pathogenetically distinct. MDM2 immunohistochemistry or fluorescence in situ hybridization studies can be used to differentiate between the two if needed.     

PDGFRa amplification in multiple skin lesions of undifferentiated pleomorphic sarcoma: A clue for intimal sarcoma metastases

A 62‐year‐old human immunodeficiency virus‐positive man was admitted for multiple cutaneous and subcutaneous nodules on his lower limbs, corresponding to an undifferentiated proliferation of spindle and pleomorphic cells, with irregular nuclei and numerous mitoses. The tumor cells were negative for a large panel of immunohistochemical markers, except CD10. MDM2 immunohistochemical staining was also negative, leading to the diagnosis of Fédération Nationale des Centres de Lutte contre le Cancer grade III undifferentiated pleomorphic sarcoma (UPS). Array‐comparative genomic hybridization showed a highly complex karyotype, with amplification of the 4q12 region, an area that contains only the platelet‐derived growth factor receptor α (PDGFRa) gene. This amplification of PDFGRa, molecular hallmark of intimal sarcoma (IS), led to the diagnosis of skin IS metastasis. A positron emission tomography showed a hypermetabolic mass protruding in the preaortic area, consistent with the diagnosis of aortic IS. Our study shows that a rare differential diagnosis in peripheral UPS can be IS skin metastasis, and underlines the importance of molecular analyses in UPS.     

Expanding the differential of cutaneous epithelioid tumors: A case of dedifferentiated liposarcoma with epithelioid features involving the skin,with review of the literature

Liposarcomas are categorized into four distinct histopathological subtypes: atypical lipomatous tumors (ALT)/well-differentiated liposarcoma (WDL), dedifferentiated, myxoid, and pleomorphic. Dedifferentiated liposarcomas account for approximately 18% of all liposarcomas, characteristically arising in the deep soft tissue. They are reported to have lower rates of metastasis compared to other pleomorphic sarcomas.^1–3 The classic histopathologic appearance is ALT/WDL admixed or juxtaposed with a predominantly nonlipogenic sarcoma. Epithelioid features are rare, appearing in as few as 3% of tumors, and have not previously been reported in a superficial location. Herein, we present a 57-year-old male with intradermal and subcutaneous metastasis of his known deep dedifferentiated liposarcoma with epithelioid features. By H&E the tumor featured cords and sheets of crowded, plump, epithelioid cells with thick nuclear membranes and prominent nucleoli, which raised a broad differential including carcinoma and melanoma. By immunohistochemistry the tumor was diffusely positive for MDM2 and CDK4, on the other hand stains for Sox10, Melan A, MITF, CKAE1/3, desmin, and S100 protein were negative. This case serves as an opportunity to raise awareness of this rare morphological subtype, which can involve the skin and mimic epithelial and melanocytic malignancies. It can be a potential diagnostic pitfall, especially if metastases are the first presentation.     

Subungual pleomorphic fibroma

BACKGROUND: Pleomorphic fibroma is a benign fibroblastic tumor characterized by pleomorphic, hyperchromatic cells or giant multinucleated cells embedded in a collagenous stroma. These cytologic features may lead to an incorrect diagnosis of malignancy. Most cases reported in the literature are located on trunk or extremities; the presentation as a subungual mass is rare. METHODS: We report an unusual case of a subungual pleomorphic fibroma in 66-year-old woman. Clinical information was obtained. Histologic examination and immunohistochemical studies were performed. RESULTS: A 66-year-old woman presented with a longstanding (40 years), subungual mass that deformed the nail of the left middle finger. Microscopic examination revealed a paucicellular tumor composed of hyperchromatic spindled, pleomorphic, floret-like giant cells embedded in haphazardly arranged collagen bundles in the dermis. No mitotic figures were seen. The tumor cells were vimentin-positive but did not stain with antibodies to S-100, cytokeratin, smooth muscle actin, factor XIIIa or CD34 negative. The diagnosis of a pleomorphic fibroma was made. Follow-up shows no evidence of tumor, 36 months after excision. CONCLUSION: Pleomorphic fibroma of the subungual region is an unusual cutaneous tumor with histologic features that may cause confusion with true sarcomas. This is only the second case reported of a subungual pleomorphic fibroma. Pleomorphic fibroma should be considered in the differential diagnosis of pleomorphic subungual tumors.     

Atypical fibroxanthoma with lymphomatoid reaction

Background: Atypical fibroxanthoma (AFX) represents an uncommon skin tumor typically occurring on sun‐damaged skin of the elderly. Histopathologic variants include spindled, clear cell, osteoid, osteoclastic, chondroid, pigmented, granular cell and myxoid lesions. To date, an atypical lymphoid infiltrate, including CD30‐positive large cells mimicking lymphomatoid papulosis, has not been described in association with AFX. Methods: The clinical and histopathological characteristics of two AFX cases inciting an atypical lymphoid infiltrate, along with immunohistochemical profiles and T‐cell receptor gamma (TCRγ) gene rearrangement results, were reviewed. Results: Lesions in both cases occurred as solitary nodules in elderly patients. Microscopically, both lesions showed a cellular proliferation composed of pleomorphic spindle cells, associated with a prominent intralesional atypical lymphoid infiltrate. The spindle cells expressed CD10 but lacked the expression of S‐100, cytokeratins and muscle markers, thereby confirming the diagnosis of AFX. CD30 highlighted a significant subset of large mononuclear cells in the lymphoid infiltrate of one case. TCRγ gene rearrangement analyses were negative for both cases. Conclusion: An atypical lymphoid infiltrate, including the one resembling lymphomatoid papulosis, associated with AFX has not been previously described. It is important to recognize the reactive nature of the infiltrate to avoid a misdiagnosis of lymphoma. Zheng R, Ma L, Bichakjian CK, Lowe L, Fullen DR. Atypical fibroxanthoma with lymphomatoid reaction.     

Cutaneous pleomorphic fibromas arising in patients with germline TP53 mutations

Pleomorphic fibromas are rare benign cutaneous neoplasms associated with deletion/loss of chromosomes 13q and 17p, where RB1 and TP53 are located, respectively. Herein, we report five cases of pleomorphic fibroma arising in patients with germline TP53 mutations, suggesting a potential link with Li-Fraumeni syndrome. All three patients were female and young (mean age 27) with a strong personal and/or family oncologic history and confirmed pathogenic germline TP53 mutations. In two patients, multiple pleomorphic fibromas were diagnosed. Clinically, the lesions arose at various cutaneous sites and were small (≤2 cm) and raised (4/5). Histopathologically, the tumors were paucicellular, composed of atypical spindled to stellate cells with hyperchromatic and variably pleomorphic nuclei. Mitotic activity was exceedingly low, although rare atypical mitotic figures were seen in one case. Immunohistochemically, the tumor cells were diffusely positive for p16 (3/3) and showed loss of Rb expression (5/5). All cases showed aberrant p53 expression (overexpression in 4, complete loss in 1). The tumors have followed a benign clinical course with no evidence of progression or recurrence. In conclusion, the development of multiple pleomorphic fibromas in a young patient may be a clue to an underlying genetic cancer syndrome involving TP53.     

An unusual presentation of dermatofibrosarcoma protuberans with pleomorphic sarcomatous transformation: potential pitfall and diagnostic strategy

Dermatofibrosarcoma protuberans (DFSP) is a low grade, superficial sarcoma characterized by a proliferation of monomorphous, spindle cells arranged in a storiform pattern and infiltrating the subcutaneous tissue. The tumor is typically CD34 positive, and shows the characteristic COL1A1‐PDGFB fusion gene, detectable either by florescent in situ hybridization (FISH) and polymerase chain reaction (PCR). We describe a case of DFSP with a focus of peculiar pleomorphic sarcomatous transformation. The focus constituted the entire bioptic tissue that was initially excised, raising considerable diagnostic problems for pathologist. The use of FISH as an ancillary technique allowed the right diagnosis.     

Cutaneous syncytial myoepithelioma: A recently described neoplasm which may mimic nevoid melanoma and epithelioid sarcoma

Cutaneous syncytial myoepithelioma is a recently described rare tumor of the dermis. It is derived and composed purely of myoepithelial cells and shows a characteristic syncytial growth pattern of neoplastic cells with little intervening stroma and no recognizable ductal structures. It represents a diagnostic challenge to dermatopathologists given its rarity and unusual immunophenotype. Molecular testing for rearrangement of the EWSR1 gene plays a significant role in confirming the diagnosis in most cases. Herein, we present 2 cases with mundane clinical presentations and challenging histopathological findings. In both cases, the lesion was composed of relatively well‐circumscribed proliferation of epithelioid and spindle cells in the superficial dermis growing in a syncytial fashion and showing focal adipocytic metaplasia. The 2 cases had slightly different immunohistochemical profiles, but shared focal positivity for S100, EMA and pan‐keratin or p63. Break‐apart FISH demonstrated the presence of an EWSR1 gene rearrangement confirming the diagnosis in both cases. We discuss the most important differential diagnoses, particularly melanocytic lesions and epithelioid sarcoma and the original diagnostic considerations that the cases were referred to us with. We also review the molecular features and spectrum of immunohistochemical findings in these lesions and their role in excluding entities in the differential diagnosis.     

Relación entre fibroxantoma atípico y sarcoma pleomórfico dérmico: histopatología de ambos y revisión de la literatura

The relation between atypical fibroxanthoma and pleomorphic dermal sarcoma has led to confusion and debate in the literature. Both tumors present on sun-exposed skin, typically on the head and neck, in patients of advanced age. Both are comprised of a variable mix of histiocytoid, spindle, epithelioid, and/or giant multinucleated cells with pleomorphic nuclei. No immunohistochemical diagnostic techniques have emerged to distinguish these tumors. Diagnosis is by exclusion. Histologically, atypical fibroxanthoma is seen as a well-circumscribed dermal nodule but there will be no evidence of extensive subcutaneous invasion, tumor necrosis, or lymphovascular or perineural invasion. Therefore, if any of the aforementioned features is present, the diagnosis would be pleomorphic dermal sarcoma. This narrative review of the literature aims to identify the distinguishing and overlapping histopathologic features of these 2 tumors as they have been described in case series.     

Dermal pleomorphic liposarcoma resembling pleomorphic fibroma: report of a case and review of the literature

Pleomorphic liposarcoma (PLPS) is a rare, high‐grade sarcoma defined by the presence of pleomorphic lipoblasts. Constituting 5% of all liposarcomas, PLPS usually arises in deep soft tissues of the extremities, with rare occurrences in the dermis and subcutis. We describe a unique case of an 85‐year‐old Caucasian gentleman with a 1 year history of a pedunculated, pink, non‐tender papule on the dorsum of his left arm, measuring 1.0 cm in maximum dimension. Biopsy revealed a dermal collection of atypical epithelioid and spindle cells superimposed on a sclerotic background, resembling a pleomorphic fibroma on low power. On high power, a central focus of discrete adipocytic differentiation with pleomorphic lipoblasts was present. Tumor cells were positive for S‐100 and negative for desmin, actin, CD68, keratin, MART‐1 and CD34. Clinicopathologic findings were consistent with PLPS and the diagnosis was made. PLPS is rarely localized to the dermis and one with low power features resembling a pleomorphic fibroma has not been previously described in the literature.     

Metastatic sarcomatoid renal cell carcinoma manifesting as a subcutaneous soft tissue mass

Metastases from visceral malignancies to subcutaneous soft tissues are relatively rare and their diagnosis requires a high level of suspicion. It is even more challenging if a metastatic lesion shows non‐specific high‐grade spindle cell morphology overlapping with various primary cutaneous and soft tissue tumors. We describe a unique case of subcutaneous metastasis of sarcomatoid renal cell carcinoma which was the first manifestation of the occult malignancy. The patient had a history of lipomas and dysplastic nevi and presented with an upper back mass. The mass, located superficially within the subcutis, was composed of atypical spindle cells arranged in a storiform pattern. By immunohistochemistry, the tumor cells were strongly diffusely positive for cytokeratin AE1/AE3 and vimentin and negative for Melan‐A, S‐100 protein, SOX10, melanoma cocktail, epithelial membrane antigen (EMA), p63, CK7, CK18, CK20, smooth muscle actin (SMA), desmin, CD34, TTF‐1, CD21, CD99 and bcl‐2. Scattered tumor cells were positive for MDM2 immunostain, but MDM2 amplification was not detected using fluorescent in situ hybridization (FISH). Co‐expression of cytokeratin and vimentin by the tumor raised the possibility of metastatic renal cell carcinoma and positivity of the tumor for PAX8 supported this hypothesis. A large renal mass was detected radiologically and the subsequent nephrectomy specimen showed high‐grade clear cell renal cell carcinoma with sarcomatoid features.     

Clear cell atypical fibroxanthoma:a clinicopathologic study

INTRODUCTION: The atypical fibroxanthoma (AFX) is considered by most authorities to represent a superficial or minimally invasive variant of malignant fibrous histiocytoma that most often presents as a solitary nodule on the sun-exposed skin of the elderly. Among the rarest variants is the clear cell AFX, a lesion which raises consideration to a differential diagnosis encompassing a variety of neoplastic and non-neoplastic clear cell proliferations. METHODS: We describe three cases of a distinctive cutaneous neoplasm arising in the sun-exposed skin of elderly patients. In all cases, formalin-fixed, paraffin-embedded tissue was available for analysis. The histology in concert with the immunophenotype was held to be diagnostic of the clear cell variant of AFX. RESULTS: All tumors comprised sheets of large cells with foamy cytoplasms and hyperchromatic, polyploid nuclei manifesting frequent and atypical mitoses. The critical cells in our cases expressed CD68 but none of CD3, CD20, CD34, S-100 protein, muscle-specific actin, factor XIIIa, Melan-A, carcinoembryonic antigen, or cytokeratin. CONCLUSION: Although typical examples of AFX provoke diagnostic consideration of spindle cell cancers of the skin (most often spindle cell melanoma, spindle cell squamous cell carcinoma, and leiomyosarcoma), the clear cell variant raises other differential diagnostic considerations instead. These include balloon cell melanoma, sebaceous carcinoma, pleomorphic liposarcoma, chordoma, parachordoma, tricholemmal carcinoma and clear cell squamous cell carcinoma. A diagnosis of AFX is one of exclusion; one must employ immunohistochemical markers to rule out the aforementioned differential diagnostic considerations. By reporting the fifth, sixth and seventh cases of clear cell AFX, we hope to alert dermatopathologists to this distinctive and unusual neoplasm, recognition of which is essential to avoid under- or over-diagnosis and inappropriate therapy.     

Retroperitoneal undifferentiated pleomorphic sarcoma having microsatellite instability associated with Muir‐Torre syndrome: case report and review of literature

Muir‐Torre syndrome represents a rare autosomal dominant familial cancer predisposition disorder defined by the occurrence of cutaneous sebaceous tumors and an internal malignancy, most commonly gastrointestinal carcinoma. Most examples of hereditary non‐polyposis cancer syndrome (Lynch syndrome), including the Muir‐Torre syndrome, are associated with microsatellite instability (MSI) and germline mutations in mismatch repair genes—most commonly MLH1 or MSH2. We present a 58‐year‐old man with Muir‐Torre syndrome and a large retroperitoneal mass (14.3 cm in greatest dimension) encompassing the left adrenal gland. Sections showed a cellular malignant tumor composed of spindle cells with a high mitotic index and lacking morphologic evidence of adipocytic differentiation. It was weakly reactive for smooth muscle actin (SMA) and negative for desmin, CD117, CD31, CD34, S100 protein and pan‐cytokeratin. Further immunohistochemical analysis revealed intact expression of MLH1 but loss of MSH2 in tumor nuclei. Compared to non‐neoplastic tissue, the tumor showed MSI in five of seven dinucleotide markers. Fluorescence in situ hybridization (FISH) failed to reveal 12q15 amplification, effectively excluding dedifferentiated liposarcoma as a diagnostic consideration. This is a rare case of a patient with Muir‐Torre syndrome who developed a related high‐grade undifferentiated pleomorphic sarcoma as the associated internal malignancy.     

Pleomorphic sclerotic fibroma: a case report and literature review.

Pleomorphic sclerotic fibroma is a benign neoplasm exhibiting features of sclerotic fibroma and pleomorphic fibroma. We report another such case. The tumor presented as a firm, 0.5-cm, flesh-colored papule on the forehead of a 72-year-old white man for an unknown duration. Histologic examination revealed a neoplasm in which the superficial portion showed features of a pleomorphic fibroma, the deeper portion showed features of a sclerotic fibroma, and a transitional area was present in between. We propose that pleomorphic fibroma, sclerotic fibroma, and pleomorphic sclerotic fibroma form a spectrum. Pleomorphic sclerotic fibroma may be used as a broad diagnostic term to encompass the spectrum.     

Cutaneous metastasis from anaplastic thyroid carcinoma exhibiting exclusively a spindle cell morphology. A case report and review of literature

Anaplastic thyroid carcinoma is a highly aggressive cancer accounting for 1–2% of thyroid malignancies. Cutaneous metastases from anaplastic thyroid carcinoma are exceedingly rare. We report a 65‐year‐old woman with anaplastic thyroid carcinoma (BRAF V600E mutation) who had lymph node metastases (pT4 N1b) treated by total thyroidectomy, postoperative radiotherapy, adjuvant chemotherapy (paclitaxel and pazopanib) and targeted therapy (vemurafenib). Nine months after initial diagnosis, radiographic studies revealed multiple pulmonary metastases. A dermatologic examination showed a solitary 1.2‐cm chest nodule. Skin biopsy from this nodule revealed infiltrative dermal spindle cells arranged in poorly formed fascicles. Immunohistochemical studies demonstrated the tumor cells to be PAX‐8 (+), pancytokeratin (+, focally), TTF‐1 (?) and SOX‐10 (?). Comparison with the patient's primary anaplastic thyroid carcinoma revealed focal areas of poorly differentiated spindle cells morphologically similar to the malignant spindle cells in the skin biopsy. Together, these findings confirmed the diagnosis of anaplastic thyroid carcinoma metastatic to skin. Cutaneous metastasis of anaplastic thyroid carcinoma composed exclusively of spindle cells broadens the histologic differential diagnosis of cutaneous spindle cell malignancies and presents further diagnostic challenges. PAX‐8 may be useful in discerning the spindle cell component of anaplastic thyroid carcinoma from other spindle cell malignancies in the skin.     

Atypical lipomatous tumor/"well-differentiated liposarcoma" of the skin clinically presenting as a skin tag: clinicopathologic, immunohistochemical, and molecular analysis of 2 cases

Liposarcomas are extremely rare in the skin. When they involve the skin, it is usually by upward spread from a subcutaneous or deeper seated liposarcoma. Very rarely, liposarcoma metastasize to the skin or arise as a primary dermal lesion. We describe 2 cases of atypical lipomatous tumor "well-differentiated liposarcoma" located in dermis. Both presented clinically as a skin tag. The neoplasms arose in a 56-year-old female and a 69-year-old male patient. Both lesions were treated by excision and reexcision. In addition to classical morphology of atypical lipomatous tumor with evidence of lipoblasts and atypical adipocytes, immunohistochemistry with nuclear murine double-minute type 2 protein and cyclin-dependent kinase-4 expression as well as fluorescence in situ hybridization analysis showing an amplification of murine double-minute type 2 protein and cyclin-dependent kinase-4 were helpful to establish the diagnosis. None of the cases recurred after surgical treatment. These 2 cases show the importance of not to misdiagnose lesions which clinically may appear to be benign.     

Primary dermal pleomorphic liposarcoma: utility of adipophilin and MDM2/CDK4 immunostainings

Liposarcoma, usually arises in deep soft tissues and pleomorphic liposarcoma (PL), is the rarest histopathologic variant. However, 15 cases of entirely dermal PL have been reported. We describe a case of a 79‐year‐old man who developed a rapidly growing nodule on his thorax. Excisional biopsy was performed and immunohistochemical studies were carried. The lesion was a well‐circumscribed dermal nodule composed of multivacuolated pleomorphic lipoblasts and atypical mitotic figures. Neoplastic cells expressed CD10 and resulted negative S100 protein, Melan‐A, MITF‐1, AE1/AE3, CD4, CD68 (PGM1), retinoblastoma gene family protein, pericentrine and lysozyme. Adipophilin stain showed the lipid contents in the cytoplasm of the neoplastic cells. MDM2 and CDK4 resulted both negative. A diagnosis of primary dermal PL was made. This case shows the utility of adipophilin immunostaining to prove the lipid contents in neoplastic cells, which has the advantage of using formalin‐fixed paraffin‐embedded tissue and making needless frozen sections and ultrastructural studies to show these findings. Negative MDM2/CDK4 staining in our case argues against the possibility of dedifferentiated liposarcoma and further supports the diagnosis of true PL.     

Extra-abdominal subcutaneous metastasis of a gastrointestinal stromal tumor: report of a case and a review of the literature

Gastrointestinal stromal tumors (GISTs) metastasize primarily within the peritoneal cavity and to the liver. Superficial soft tissue metastases occur in about 1% of advanced GIST and are mostly associated with abdominal laparotomy scars and advanced disease. Extra-abdominal subcutaneous metastases of GIST have not been previously reported. Subcutaneous spindle cell tumors constitute a diagnostic challenge of which the differential diagnostic list can be limited by recognition of morphological, immunohistochemical en molecular genetic patterns. A 69-year-old woman presented with a fast growing subcutaneous nodule on her right upper arm. She was known with an imatinib-resistant advanced GIST, treated with sunitinib. The nodule was excised. Histopathological examination revealed a sharply demarcated tumor nodule in the subcutaneous fat with slightly spindled tumor cells, with pleomorphic nuclei and multiple mitoses. There was a hemangiopericytomatous vascular pattern. The cells stained positive for CD117 (KIT) and CD34. No KIT or platelet-derived growth factor receptor-α mutations were detected. We report the first case of an extra-abdominal subcutaneous metastasis of GIST. Although rare, metastatic GIST should therefore be included in the differential diagnosis of subcutaneous spindle cell tumors. A comparative survey of the histological, immunohistochemical and molecular genetic features of spindle cell tumors of the subcutis and a review of the literature is presented.     

Congenital Myxoid and Pigmented Dermatofibrosarcoma Protuberans: A Case Report

Dermatofibrosarcoma protuberans (DFSP) is a low‐grade, mesenchymal, spindle cell tumor. In addition to the classical form characterized by a storiform pattern of tumor cells, pigmented (Bednar's tumor) and myxoid variants can be observed. Classical DFSP and Bednar's tumor are easily diagnosed. The myxoid variant represents a diagnostic challenge. Pigmented and myxoid variants are rare and thus far have never been reported in association in congenital DFSP. We came across a unique DFSP that was, at the same time, congenital, pigmented, and myxoid. The tumor was surgically excised with broad free margins and no recurrence. The differential diagnosis with other entities such as giant cell fibroblastoma, CD34‐positive plaque‐like dermal fibroma, superficial plaque‐like CD34 DFSP, and neurocristic hamartoma is discussed. The recognition of this hybrid variant of congenital DFSP is important to avoid under‐ or overtreatment.