Search

Dermatofibrosarcoma protuberans is a quite rare local aggressive tumor of dermis and subcutis, revealing characteristic morphology and chromosomal translocation (17; 22)(q21;q13) with gene fusion COL1A1-PDGFB. The tumour almost never metastasizes and complete excision signs an excellent prognosis. Approximately in 10% of cases, dermatofibrosarcoma undergoes a fibrosarcomatous transformation associated with metastatic disease and worse prognosis. In this paper, we refer a case of a male patient with subcutaneous tumor in back region, in which the small biopsy lead to diagnosis of a spindle cell sarcoma. However, only the histopathological examination of the entire tumor in the material from the radical surgery detected the dermatofibrosarcoma protuberans with fibrosarcomatous transformation. Both components of the tumor showed the characteristic genetic alteration. Identification of fibrosarcomatous component within the DFSP matters in prognosis. Distinction between fibrosarcoma arising within the dermatofibrosarcoma protuberans and fibrosarcoma arising de novo is of therapeutic consequence: the patients with metastatic or inoperable DFSP with fibrosarcomatous transformation may profit form imatinib treatment.

35-year-old woman suffered prolonged pain in the left shoulder, where an aggressively growing tumor of the proximal humerus was revealed thereafter. The lesion caused massive osteolysis of the metaepiphysis with cortical disruption, but no soft tissue extension was evident. Given the unsatisfactory effect, the ongoing neoadjuvant chemotherapy was prematurely ceased and the resection 13 cm long segment of bone with modular prosthesis replacement followed. Histologically, clear-cut malignant tumor with both the presence of numerous reactive osteoclast-like giant cells and geographic structural deposition of chondroid matrix bore a close resemblance to chondroblastoma. Dominant cellular composition formed solid mosaic clusters of large, atypical, frequently binucleated cells with voluminous eosinophilic cytoplasm. Impressive nuclear pleomorphism was accentuated by both the grooving and atypical mitotic figures. Thorough sampling disclosed limited, but sharply contrasting parts, where biphasic arrangement of small uniform stromal elements together with regularly distributed, reactive osteoclasts suggested putative precursor giant cell lesion. Except the osteoclasts, all matrical and stromal cells were strongly SOX9 and D2-40 positive; in contrary desmin, SATB2, S100 and p63 yielded completely negative results. Detected H3F3A c.103G>T mutation in exon 2 finally established true nature of that peculiar neoplastic proliferation and lead to descriptive term of primary chondroblastoma-like malignant giant cell tumor. In the setting of all the microscopic variability, histogenesis and complex differential diagnosis of skeletal (malignant) giant cell lesions, there are discussed e.g. aggressive/malignant chondroblastoma, chondroblastoma-like osteosarcoma or giant cell-rich osteosarcoma and practical impact of specific mutational analysis results as well.

The literature is reviewed regarding of a rare molecularly defined group of sarcomas with rearrangement of both CIC and BCOR genes, which were originally placed into the EWSR1wt Ewing-like category. Personal experience with three cases demonstrating difficulties of this issue is added. Both groups of lesions differ not only by age and topography, but also vary in both the prognostic and the predictive parameters. CIC-rearranged tumors are very aggressive and almost never occur in the skeleton; in contrary, the BCOR-rearranged ones are predominantly bone tumors in young males behaving even better than classical Ewing sarcoma. From the morphologic point of view, it turned out to be a salient finding that these types of neoplasm might leave canonical morphotype of small blue round cell sarcoma. Instead of it, they are not uncommonly characterized as a relatively uniform spindle cell proliferation with prevailing myxoid transformation deserving much broader differential diagnosis. Our three cases reports display difficulties in reaching the correct diagnosis even by implementing sophisticated molecular techniques in routine practice. Notwithstanding of exhaustive molecular assays used, one may still encounter a lesion where original descriptive term Ewing-lie sarcoma remains uncorrected.

Presented is a case of 59-year-old woman with longstanding neck pain who has been promptly operated for spinal cord compression. Imaging studies disclosed ill-defined cervical paravertebral soft tissue mass at the level of vertebra C5/6 abutting left-sided intervertebral joint and destroying neighboring both vertebral arch and processus spinosus. Submitted specimen was interpreted as a possible metastatic skeletal process by clinicians and referring pathologist favored diagnosis of giant cell tumor/osteoclastoma of the bone. Microscopic features were consistent with giant cell lesion where uniform mononuclear mosaic stromal component dominated the unevenly distributed loose clusters of osteoclast-like giant cells frequently imparting appearance of peculiar pseudoalveolar spaces. Additionally, alternating geographic xanthomatous and densely hyalinized/ osteoid-like zones with speckled, coarsely granular haemosiderin pigment completed the variegated structural composition. The tumor infiltrated adjacent striated muscles; either original bone structures and/or extracellular matrix deposits were not identified. Immunohistochemical stains with p63, SATB2, desmin, EMA, clusterin and S100protein turned out to be completely negative. FISH analysis revealed no rearrangement of CSF1 gene. The diagnosis of the diffuse tenosynovial giant cell tumor was rendered.

The authors present a unique case of small cell variant of clear cell sarcoma of soft parts in a 42-year old woman. The tumor originally arose in the right flank of the soft tissues and ultimately developed both a local recurrence and multiple distant skin metastases two years and ten months thereafter. Nonspecific morphology of small blue round cell tumor was preserved at all microscopically verified sites and initially led to the spectrum of erroneous diagnoses such as an extraskeletal myxoid chondrosarcoma, Ewing sarcoma as well as malignant melanoma. The distinctive features of clear cell sarcoma such as fascicular nested growth pattern, spindling, clear cell change and/or eosinophilic cytoplasm were not disclosed even by extensive sampling. Immunohistochemically, the tumor expressed only S100protein and HMB45; all other markers (CD99, FLI1, cytokeratins, EMA) were completely negative. The molecular analysis carried out in one of the cutaneous metastases revealed translocation t(12;22) (EWSR1-ATF1) and ultimately led to the correct diagnosis of unusual Ewing-like clear cell sarcoma. Discussed is the implementation of molecular tests in routine diagnostics considering the existence of both histologically and biologically different tumors with an identical pathogenic molecular background.

The authors present five cases of periosteal osteosarcoma located in the femur (4) and tibia (1) in children and young adults (1 female and 4 males) with an age range of 9 - 23 years (mean age 15 years). Radiographs in all cases showed a broad-based soft tissue mass attached to the cortex with periosteal reaction and in two of them cortical disruption with extensive medullary involvement. Follow-ups were available in four cases (range 11 - 73 months) and revealed pelvic metastasis after 15 months with ultimately rapid dissemination and death in a 9-year-old girl and metastasis to the humerus after 13 months in a 15-year-old boy. The former tumor widely extended into the medullary cavity and an amputation was carried out, the latter had a pure juxtacortical position and an en block resection was performed; both of them were treated with chemotherapy. All the lesions displayed distinctive structural patterns combining a large island of tumorous cartilage and hypocellular, bland-looking myxoid mesenchymal stroma with abrupt transition between both components. Contrary to conventional osteosarcoma, the delicate flocculent osteoid deposits were produced by innocuous stromal cells lacking apparent atypia. They were strictly situated outside the prevailing chondroid areas and disclosed sometimes only after a meticulous search. Immunohistochemical detection of SATB2, S100protein and D2-40 assisted effectively not only in recognition of the real stromal histogenetic derivation, but also in distinction of true differentiation of a heavily mineralized extracellular matrix. Molecular analysis revealed no IDH1/2 mutation in four examined cases. Regardless of unique low-grade morphology in rare periosteal osteosarcoma, an aggressive therapeutical approach similar to conventional osteosarcoma is justified, particularly in the case of a medullary extension.

The authors present two cases of Ewing-like sarcoma of the humerus and femur of a 12-year-old boy and a 28-year-old male, respectively. Identical morphology in both tumors consisted of multiple solid nests with a mosaic collection of small, round, uniform cells with clear cytoplasm and no apparent nuclear atypia. A monotonous structural arrangement, including both rich vascularity of bordering septae and significant admixtures of eosinophil leucocytes, resulted in a final organoid "neuroendocrine-like" pattern. Immunohistochemistry revealed diffuse strong CD10, CD99 and CD138 positivity. Detailed molecular analysis in both tumors confirmed translocation t(20;22) resulting in an EWSR1-NFATc2 fusion gene. Additionally, this translocation was accompanied by amplification of the proximal part of the genes and surrounding areas. Clinically, both neoplasms behaved aggressively and they were primarily chemoresistant. Four years later, the patient with the lesion in the humerus developed a massive local recurrence with a disruption of osteosynthesis. The last follow-up disclosed suspicious metastatic deposits in the lung. The boy with the femoral tumor underwent a total femoral prosthesis and there are no signs of local or systemic recurrence after 11 months of follow-up. The authors discuss the taxonomic placement of these rare examples of Ewing-like sarcoma family in the light of new molecular discoveries.

Unlabelled: A 76-years-old woman underwent a partial mastectomy and a low-grade malignant homologous phyllodes tumor measuring 45 mm in maximum diameter was diagnosed. Beyond its typical dual composition the tumor displayed extensive intraductal squamous metaplasia. Approximately in one third of the lesion the original mesenchymal component cytologically and structurally changed which ultimately led to seeming stromal overgrowth. The loose storiform background contained isolated larger atypical elements with ample eosinophilic cytoplasm and obvious mitotic activity. This final fibromatosis-like arrangement was completed either by multiple dispersed abrupt squamous morules or just by pearl-like abortive form of squamous differentiation. Conventional in situ or invasive ductal carcinoma was not present. A combined expression of both low and high molecular weight cytoketatins, S100 protein, p63, CD10 and GFAP confirmed the incomplete basal/myoepithelial phenotype and ultimately led to the diagnosis of a spindle cell metaplastic carcinoma arising in a phyllodes tumor - a neoplasm unpublished so far. A review of the literature concerning epithelial malignancies originating from a milieu of phyllodes tumor guides discussion/speculation over the possible histopathogenesis of this vanishingly rare lesion., Keywords: breast - phylloid tumor - phyllodes tumor - spindle cell sarcomatoid/metaplastic carcinoma - squamous metaplasia.

Backgrounds: The cancerogenic effect of ionizing radiation was documented just several years after it started to be used as a treatment option. Ionizing radiation produces a small but detectable risk of carcinoma as well as bone and soft tissue sarcomas. Over the past 20 years angiosarcomas arising from the area of the irradiated breast have been reported with increasing frequency as the number of women undergoing the breast conserving surgery with consecutive radiotherapy has increased also. Angiosarcomas can originate from either lymphatic or capillary endothelium, namely lymphangiosarcomas and haemangiosarcomas. The most of haemangiosarcomas arising from the breast skin developed in the irradiated area after breast conserving procedure--secondary angiosarcomas. Lymphangiosarcoma is typically associated with longstanding extremity lymphedema--Stewart-Treves syndrome., Cases: We report three cases of angiosarcomas which occured in this region after breast conserving treatment and we also review the literature., Conclusion: Paradoxically, the decrease in the use of radiotherapy to the post-mastectomy chest wall and the axillary area is expected to reduce the incidence of angiosarcomas, while the increase in the use of breast conserving procedure plus radiotherapy could lead to increased incidence of angiosarcomas in the residual breast tissue. Special attention should be paid to skin leasions and changes occuring after breast conserving treatment and especially to the ones with the skinthickening. The early detection and diagnosis has the crucial prognostic value.

30-year-old woman admitted for acute abdominal pain with peritoneal signs was immediately operated with findings of hemorrhage in small pelvis. Laparotomy revealed hemorrhagic, friable mass 3 cm in maximum diammeter arising from the uterine horn. The neoplasm broadly invaded myometrium with no evidence of endometrial cavity involvement. Microscopically, the tumor displayed solid mosaic pattern and consisted of large epithelioid cells with ample eosinophilic, finely granular cytoplasm ongoing apparent clear cell change elsewhere. There was marked nuclear irregularity with numerous atypical mitotic figures and multiple bizarre giant elements dispersed throughout the lesion. Unusual complex phenotype included co-expression of vimentin, smooth muscle actin, desmin, HMB45, Melan A, CD10 and EMA. No obvious stigmata of tuberous sclerosis were found and a five months follow-up after chemotherapy indicated no progression of disease. With some uncertainty the tumor was finally rendered as pleomorphic leiomyosarcoma with peculiar melanocytic differentiation. PEComa as an alternative term was coined. Expressed are both difficulty in explaining the histogenesis and ambiguity of the existing terminology of the uterine tumors with mixed myoid and melanocytic phenotype. Reviewed is the literature and discussed is the differential diagnosis.

Presented is an unusual case of a benign mesenchymal stromal tumor of the breast in an 81-year-old male. The basic appearance of the lesion simulated benign schwannoma and was misinterpreted as a low-grade myxoid liposarcoma initially. Well-circumscribed, gray-white mass measuring 35 mm in maximum diameter was discovered deep in the parenchyma of the completely removed breast. Microscopically, the lesion consisted of myxoid, richly vascular background where dominated oval or spindle cells with impressive palisading replicating that of benign schwannoma. Rarely, the large multinucleated (floret-like type) cells were visible; no nuclear atypia or mitotic figures were found. Immunohistochemical examination confirmed expression of estrogen and progesterone receptors, antigen Bcl2 and also focal desmin positivity. Clinical examinations disclosed no objective reason for possible hyperestrinism; no other therapy followed and the patient is free of disease 19 months after operation. On the background of both detailed review and differential diagnosis of benign, so-called stromal tumor of the female breast, the rarity of this microscopic finding in male is documented.

Presented are two cases of systemic mastocytosis in 46- and 63-year-old women, where the correct diagnosis was established in randomly disclosed cervical respectively intraabdominal lymphadenopathy. Both cases lacked characteristic skin and systemic mast-cell mediator symptoms at the time of histologic diagnosis. The first case was classified as a indolent systemic mastocytosis without any proven genetic alteration, the second one met the criteria of aggressive systemic mastocytosis with eosinophilia, where the point mutation asp816val in c-kit gene was confirmed and the patient responded unexpectedly well to Gleevec. Discussed are both conventional morphological differential diagnosis of mastocytosis in lymph nodes and recent advances in genetics of these systemic clonal mast cell proliferations. The latter not only outlines the oncopathogenesis but, in particular, also provides important prognostic and biological implications of this peculiar disease.

Described are two epithelial lesions of the breast displaying extremely rare, widespread acinic cell-like differentiation (metaplasia). Two women, 70 and 40-year-old, one with invasive ductal papillocarcinoma, the other one with conventional intraductal hyperplasia without atypia, both demonstrated massive diffuse, PAS positive, granular eosinophilic transformation of the cell cytoplasm. This unusual cell appearance closely simulated acinar cells in normal serous salivary gland/acinic cell carcinoma or Paneth cells. Both extensive expression of lysozyme and finding of numerous zymogen granules ultrastructurally confirmed the acinic cell-like fenotype. Discussed is differential diagnosis of the breast neoplasm containing overt eosinophilic and granular cytoplasm. Reviewing literature and comparing our unique finding of unusual salivary-type differentiation in conventional ductal hyperplasia of the breast, biologic implications are considered.

Five cases of dedifferentiated chondrosarcoma of bone are presented. Three women and two men of age ranging from 57-72 years (median 63 years) suffered from tumors located in femur (2), scapula (1), humerus (1) and pelvis (1). They were all bulky tumors destroying the bones and infiltrating into the adjacent soft tissues in maximum diameter from 5-20 cm (median 12 cm). Both the short clinical histories lasting from 2-24 months (median 5 months) and persistent pains unrelieved by acylpirin were constant findings in all the cases. Four patients died of metastatic disease (mainly to lungs) with median survival of 8 months. All cases were the so-called "de novo" dedifferentiated chondrosarcomas without clinical or morphological evidence of the primarily benign or malignant chondroid lesions. The tumors displayed a typical dual composition with an abrupt interface between chondroid and nonchondroid components. The chondroid tissue resembled G1 chondrosarcoma in three cases, G2-3 chondrosarcoma in two cases. The second nonchondroid mesenchymal portion had the appearance of undifferentiated pleomorphic sarcoma in three cases, rhabdoid and giant cell tumor-like in one case. The new data and evidence provided by molecular biology dramatically changed the opinions of histogenesis of this unique neoplasm. At present, there is a generally accepted idea of common origin of both portions from a primitive stem cell. Therefore, this peculiar tumors should not be viewed merely as dedifferentiated conventional chondrosarcomas.

Described are two cases of angiotropic lymphoma where eventually autopsy elucidated nonspecific neurologic symptoms. One patient suffering ambiguous encephalitic syndrome died three months later, the second one passed away after an unusually long three-year period of progressive dementia and cumulative motoric dysfunction. The autopsy disclosed pure intravascular malignant lymphoid aggregates (LCA, CD 20, Bcl 2-positive) in the brain and kidney of both patients. In the patients with the longer disease period, a dissemination to lung was also found. Definitive diagnosis was issued as a B cell type of angiotropic lymphoma. Skin, lymph nodes, spleen, and bone marrow were not affected in any case. The clinical differential diagnosis algorithm did not involve this rare etiology in these particular uncommon neurologic cases and even brain biopsy performed in both women did not recognize the substantiality of the disease.

The authors report about clinico-morphological features in four cases of spindle-cell metaplastic carcinoma of the breast, closely mimicking benign soft tissue fibromatosis or nodular fasciitis. All patients were females aged 54-72 years with a palpable nodule within the breast, 20-35 mm in size. Histologically, the tumor infiltrated surrounding tissue; it consisted of spindle cells with relatively bland morphology, arranged in a fascicular, storiform or random fashion. Mitotic activity was low, focally the tumors revealed regressive changes (hyalinization, myxoid degeneration). Cytokeratin expression was proven in all four cases. In two patients the tumor metastasized and the patients died of it; this fact confirms recently published data that despite its deceptively benign appearance, fibromatosis--like carcinoma of the breast is undoubtedly a malignant process with potentially aggressive behaviour. Differential diagnosis of this unusual variant of metaplastic breast carcinoma is discussed together with related therapeutic issues.

There is described fifty-year-old woman with so called malignant adenomyoepithelioma of the breast. The conventional benign looking adenomyoepithelioma with biphasic tubular pattern continually fused to unequivocal invasive lesion which by immunophenotype turned out to be myoepithelial carcinoma. The 15 months follow up was uneventful. Extensive literature overview and terminology consideration is presented. The paper discusses biologic consequences of this rare breast lesion and its close resemblance to almost identical lesions in the salivary glands and skin adnexa.

Sclerosing epithelioid fibrosarcoma (SEF) was first described in 1995 and since then 39 cases have been reported. Here we describe 6 cases of SEF (3 in women and 3 in men). The patients aged from 22 to 79 years. The tumours were located in soft tissues of the extremities (in 3 cases in the lower, in 2 instances in the upper extremity) and of the trunk (in 1 case). The lesions were partially nodular, of gray-white colour, and hard in consistency. Histologically, they were composed of epithelioid round to ovoid small cells with a sparse cytoplasm and a very low mitotic activity. The tumour cells formed cords and alveoli or were scattered individually within a dense hyalinized collagenous stroma. The neoplasms also contained foci of conventional fibrosarcoma, necrosis, calcification, and metaplastic bone. On immunohistochemistry, the neoplastic cells were positive for vimentin. Two cases were immunoreactive for epithelial membrane antigen and one tumour also for cytokeratins. The proliferative activity, assessed by MIB 1 antibody (Ki-67), was detected in 1-6% of neoplastic cells in primary tumours. Follow-up information was available in 5 patients. In two cases, there were local recurrences and distant metastases (in the lungs, upper extremity, and mediastinum). One of these patients died of SEF. The differential diagnosis of this relatively low-grade fibrosarcoma is broad and includes, along with a variety of benign and malignant soft tissue lesions, infiltrating carcinoma, and, to a lesser extent, sclerosing lymphoma.

The paper discusses two unusual cases of solitary skeletal plasmacytoma and multiple myeloma presenting clinically as a metastatic disease in cervical lymph nodes. The pathology report of lymph node plasmacytoma initiated an extensive clinical search for eventual discovery of skeletal disease in both patients. We are not aware of any report in the literature dealing with this issue (Medline 1970-2000). The early involvement of lymph nodes by plasmacytoma with the appearance of undifferentiated neoplasm is challenging and poses great difficulties in correct diagnosis; this is almost impossible from hematoxylin eosin slides. The problem is that one has to think about the rare possibility of metastasing plasmacytoma in differential diagnosis of anaplastic tumors in lymph nodes. Immunohistochemistry and clinical records are very helpful in making a final diagnosis.

Presented is a typical case of Erdheim-Chester disease (ECD) wherein the severe pulmonary manifestation led to an open lung biopsy and eventual morphologic recognition of the nonspecific clinical symptoms. The pulmonary involvement is described in almost 20% of cases and is prognostically unfavourable. About 20 cases of Erdheim-Chester disease were published and more than half of them had lethal outcome. The ECD affecting seriously lungs appears as non-specific interstitial lung disease and usually does not enter the broad clinical differential diagnosis. A detailed bibliography with special attention to the pulmonary involvement by this enigmatic disease is presented.

From the collection of 2500 cases of renal epithelial tumors in our files, 102 renal oncocytomas were analyzed for size, multifocality and a morphologic spectrum of the growth pattern. The size of the tumors ranged from 1.5 to 13 cm in diameter, with a mean of 6.3 cm. Three cases were multifocal, four cases were combined with another primary renal tumor (1x angiomyolipoma, 1x conventional renal carcinoma, 2x papillary renal cell carcinoma). A central fibrosis or a scar was noted in 13 cases, and there was a gross area of hemorrhage in 11 cases. In 4 cases extensive necroses were recognized. Histologically, an alveolar pattern was noted in 70 cases. A tubular pattern was revealed in 31 cases and an unusual tubopapillar ("glomeruloid") pattern was noted in one case. Foci of atypical nuclei were identified in 58 cases. In 4 oncocytomas broad areas of clearance of the oncocytes were found. Psammoma bodies were recognized in 9 tumors and foci of ossification were present in 4 cases. Intracellular and extracellular hyaline globules were noted in two cases. Renal oncocytoma has a variable morphologic spectrum, and its diagnosis should be based on an analysis of structural and cytologic features. Differential diagnosis of renal oncocytomas with various tumors of the kidney which contain granular cytoplasm is discussed. These tumors with granular cytoplasm include conventional renal cell carcinomas, chromophobe cell carcinomas, and rare examples of papillary renal carcinomas.

Chromophobe cell renal carcinoma is a relatively rare primary tumour of the kidney. We present two cases of sarcomatoid transformation in this type of renal cell carcinoma. Described transformation in chromophobe renal cell carcinoma has been reported previously only in four publications. We present a very unusual aggressive recurrence of one of our cases and introduce the first case of sarcomatoid carcinoma arising from chromophobe cell renal carcinoma of the kidney with rhabdomyoblastic differentiation.