Storiform Growth Pattern Research Articles

ALK-rearranged, CD34-positive spindle cell neoplasms resembling dermatofibrosarcoma protuberans: a study of seven cases.

The majority of dermatofibrosarcoma protuberans (DFSP) harbour PDGFB or PDGFD rearrangements. We encountered ALK expression/rearrangement in a PDGFB/D-negative CD34-positive spindle cell neoplasm with features similar to DFSP, prompting evaluation of ALK-rearrangements in DFSP and plaque-like CD34-positive dermal fibroma (P-LDF). We searched the archives of academic institutions for cases previously coded as DFSP and P-LDF. NGS-naïve or PDGFB-negative DFSP were screened for ALK (clone D5F3) expression by immunohistochemistry. NGS or ALK FISH was performed on ALK-positive cases. Methylome profiling studies were performed and compared with conventional DFSP. One case of "DFSP" and two "P-LDF" with ALK expression were identified from the archives, while four cases were detected prospectively. These seven cases (6F:1M; 8 months to 76 years) arose in the dermis of the arm (two), scalp, eyelid, thigh, abdomen, and shoulder and ranged from 0.4 to 4.2 cm. Tumours were composed of spindled cells and displayed a storiform growth pattern. Cytologic atypia was absent, and mitotic figures were scarce (0-2/10 HPFs, high power fields). The lesional cells were diffusely positive for CD34 and ALK and negative for S100 protein. By NGS (n = 5), ALK fusion partners included DCTN1 (2), PLEKHH2, and CLIP2 in DFSP-like cases and FLNA in P-LDF-like lesions. ALK FISH was positive in one (of two) cases previously labelled P-LDF. Methylome profiling of two (of three) ALK-rearranged DFSP-like tumours showed clustering with conventional DFSP in the UMAP dimension reduction plot. To date, no tumour has recurred (n = 2; 26, 27 months). We describe a cohort of novel ALK-rearranged tumours with morphologic features similar to DFSP.

Unilateral Primary Breast Dermatofibrosarcoma Protuberans with Negative COL1A1-PDGFB Fusion on Fluorescence In Situ Hybridization

Abstract Introduction/Objective Dermatofibrosarcoma protuberans (DFSP) is a superficial and locally aggressive cutaneous soft tissue sarcoma. In most patients, DFSP arises from the trunk and proximal extremities with breast being an uncommon location. Although they rarely metastasize (<5%), DFSP variants tend to recur locally. Most molecularly characterized cases have been defined by the translocation t(17;22)(q21.3;q13.1), which yields a fusion of the COL1A1 and PDGFB genes. In routine practice, dual fusion or break-apart fluorescence in situ hybridization (FISH) for the COL1A1-PDGFB fusion gene is the most widely used screening method for DFSP. However, in ~4% of typical DFSP cases, routine FISH screening is negative. In some of the DFSP cases negative for COL1A1-PDGFB fusion gene by FISH, RNA sequencing has identified two novel gene fusions, COL6A3-PDGFD and EMILIN2-PDGFD, with the former having a predilection for the female breast. Methods/Case Report We present a 32-year-old woman who underwent a biopsy for a 3.4 cm echogenic firm mass in her right breast. Histology showed a cytologically-uniform spindle cell neoplasm with fibroblastic morphology. The neoplastic cells displayed a storiform growth pattern and honeycomb-like infiltration of the adipose tissue. Immunohistochemically, the neoplastic cells expressed CD34 and vimentin and were negative for AE1/AE3, p63, S100, CD31, SMA, β-catenin, and STAT6. PDGFB break-apart FISH was negative. Based on the histologic and immunohistochemical findings, a diagnosis of DFSP was rendered. FISH for PDFGD rearrangements or RNA sequencing targeting PDGFD was not performed at this time. Results (if a Case Study enter NA) NA. Conclusion Awareness is warranted for the rare variant of DSFP with a predilection for female breast, which is characterized by a novel gene fusion not detectable by routine FISH used for DFSP screening.

S2125 Short Time Recurrence of Retroperitoneal Desmoid Tumor in Patient With Familial Adenomatous Polyposis

Introduction: A Desmoid Tumor (DT) is a locally invasive, non-metastatic mesenchymal stem cell tumor that typically manifests as a soft tissue mass occurring in muscles, fasciae and aponeuroses. We present a case of a patient with recurrence of a retroperitoneal DT shortly after resection. Case Description/Methods: A 34-year-old male presented with abdominal pain found to have a large (11 × 14.4 * 14 cm) intrabdominal mass. IR transcatheter biopsy of the mass confirmed DT. He underwent bidirectional endoscopy and found to have more than hundred adenomatous colon polyps. Genetic testing confirmed APC mutation. Patient was diagnosed with DT associate with Familial Adenomatous Polyposis (FAP). He underwent radical resection of mesenteric mass and small bowel (20 cm of terminal ileum), omentectomy as well as total colectomy with ileorectal anastomosis. There was no evidence of lymphoid involvement. About 3 months later, he was re-admitted for increased abdominal girth with abdominal pain. MRI scans demonstrated a new, extensive, lobulated soft tissue mass occupying the entire abdominal cavity measuring 23.4 × 12.5 × 24.2 cm. Biopsy of the mass confirmed recurrent DT. Given the large size and proximity to the superior mesenteric artery, the mass was deemed to be unresectable. Patient was initially started on palliative systemic treatment with liposomal Doxorubicin. Due to lack of response, he was then switched to weekly methotrexate and Vinblastine (Figure). Discussion: DTs are rare neoplasms, making up only 0.03% of all neoplasms and 3% of soft tissue tumors. They typically include the abdominal wall, extremities, and mesentery. Although the etiology of DTs is not well known, there are several risk factors that are associated with their occurrence. Genetic syndromes such as FAP and Gardner syndrome have a well-known association with DTs. Other associations include antecedent trauma to the site of the lesion, pregnancy, and female sex. Numerous studies have been done assessing the efficacy of surgery, radiotherapy, and chemotherapy in managing DTs. However, none have shown conclusive benefit. The recurrence rate, particularly following surgical management, has been found to be as high as 77%. Given the lack of definitive management and high recurrence rates, treatment options should likely include combination of both surgical intervention and systemic treatment after discussing options and adverse effects of treatment with the patient.Figure 1.: A, Contrast enhanced CT axial through the lower abdomen demonstrating recurrence of large mass now occupying the majority of the abdominal cavity (black star); B, Spindle cell lesion, with fascicular and loose storiform growth patterns (H&E, 40×) prior to resection; C, Recurrent tumor with pathology demonstrating spindle cell lesion with more edema and/or myxoid stroma.

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.

Low-grade myofibroblastic sarcoma of the levator scapulae muscle: a case report and literature review

BackgroundLow-grade myofibroblastic sarcoma (LGMS) is described as a distinct atypical myofibroblastic tumor often with fibromatosis-like features and predilection for the head and neck, especially the oral cavity and larynx. LGMS arising in the levator scapulae muscle is extremely rare.Case presentationA 69-year-old woman was admitted to our hospital because she noticed a hard mass in her left neck six months prior. Magnetic resonance images (MRI) showed a soft tissue tumor of the left levator scapulae muscle. A core needle biopsy showed cellular fascicles or a storiform growth pattern of spindle-shaped tumor cells with minimally atypia. Immunohistochemistry revealed focally positive for α-smooth muscle actin (α-SMA), negative for S-100, and a low-grade spindle cell sarcoma was suspected. Following a biopsy, the tumor was resected with a wide surgical margin. Immunohistochemical staining was a positive for vimentin and α-SMA and negative for desmin, CD34, nuclear β-catenin, and h-caldesmon. LGMS diagnosis was determined based on the histopathological findings. The patient was alive with no evidence of disease eight years after the surgery.ConclusionsTo the best of our knowledge, this is the first case report of LGMS arising in the levator scapulae muscle. In addition to the case report, 48 reports with 103 LGMS cases are reviewed and discussed. In previous reports of LGMS, there were 43 females and 60 males, with a mean age of 43.0 years (range, 2–75). There were 13 (12.6%) patients aged < 18 years, 67 (65.1%) patients aged 18 to 59 years, and 23 (22.3%) patients aged ≥60 years. The average tumor size was 4.4 cm (range: 0.4–22.0). The commonest sites of LGMS was the tongue. Tumor growth patterns were evaluated in 52 cases, and 44 cases (84.6%) showed infiltrative growth patterns. Local recurrence was 26.7%, and distant metastasis was 4.4%. Because of the locally aggressive feature, it is important to diagnose LGMS with biopsy and to excise the tumor with an adequately wide margin.

Phenotypic variation of thymic epithelial cells and partial spontaneous regression in thymoma of a cow

Thymoma was recognized in a 12-year-old Holstein dairy cow presenting with no significant clinical signs. The animal was conventionally slaughtered at an abattoir and, on postmortem examination, a spherical tumor mass was found in the anterior region of the mediastinum. Histologically, the tumor was fibrously encapsulated and exhibiting varying-sized cystoid cavities containing serous fluid and necrotic and hemorrhagic foci. No architectural features showing distinct characteristics to a sufficient degree to allow identification of the thymus or other organs could be seen. The tumor showed diffuse solid sheet-like or nodular patterns of proliferation and consisted of a dual cell population: one was neoplastic epithelial cells that were immunohistochemically positive for cytokeratin, and the other was T lymphocytes that exhibited positive immunohistochemical staining with CD3. This finding enabled a diagnosis of mixed thymoma to be made. Neoplastic epithelial cells represented a wide spectrum of phenotypic expression, including (1) spindle shaped cells with a chiasmus-like, interlacing fascicular, or storiform growth pattern; (2) small, round to oval cells with scant cytoplasm showing indistinct boundary of cells; (3) large cells arranged in a solid sheet-like pattern; (4) vacuolated cells similar to signet ring cells; (5) clear cells that had defined cell membranes; and (6) occasional formation of micronodules composed of neoplastic epithelial cells. In addition, some areas of the tumor exhibited features of partial spontaneous regression characterized by collapse or disintegration of tumor tissues in close association with fibrocollagenous connective tissue deposition. Even if the morphology of thymic epithelial cells in thymoma is known to display variable appearance, it is likely to be unusual that, in the current bovine case, such thymic epithelial cells exhibited a wider spectrum of phenotypic expression within a single tumor. This salient histomorphological heterogeneity shown by thymic epithelial cells might have presumably been associated with innate characteristics specific to pluripotent thymic epithelial cells during thymoma tumorigenesis.

Rat malignant fibrous histiocytoma (MFH)-derived cloned cell lines (MT-8 and MT-9) show different differentiation in mesenchymal stem cell lineage

Malignant fibrous histiocytomas (MFHs) show a storiform growth pattern consisting of fibroblastic, histiocytic and undifferentiated mesenchymal cells with possible multipotency. Because MFH-like tumors are induced experimentally by some chemicals and materials, it is important to know the histogenesis of MFHs. We analyzed in vitro and in vivo characteristics of two cloned cell lines (MT-8 and MT-9) established from a spontaneous MFH found in an aged F344 rat. MT-8 and MT-9 cultured cells and their tumors induced in syngeneic rats by injection were investigated morphologically, and their tumors were evaluated by immunohistochemistry. Gene expression profiles of their cultures and induced tumors were analyzed by the comprehensive gene analysis. MT-8 cells had less developed organelles and the induced tumors represented histological characteristics of undifferentiated sarcoma (sarcoma not otherwise specified (NOS)), whereas MT-9 cells had relatively well-developed intracytoplasmic organelles such as endoplasmic reticulum, mitochondria and lysosomes and the tumors showed a storiform growth pattern typical of MFHs. MT-8 and MT-9 tumors were immuno-positive for vimentin, and the reactivity for stem cell markers (nestin, CD90, CD34, and A3) appeared to be greater in MT-9 tumor cells, and their tumor cells did not react to markers for well-differentiated cells of epithelial, myogenic and neurogenic tissues except for faint reaction for S-100 protein in MT-9 tumors. The gene analyses revealed that genes relating to “cell differentiation” were more activated in MT-9 than MT-8 tumors, whereas those involved in “cell cycle” were greater in MT-8 than MT-9 tumors. In MT-8 and MT-9, additionally, genes involved in “cell differentiation” were much greater in their tumors than in their cultures. These findings indicate that MT-8 cells are poorly differentiated mesenchymal stem cells which induce sarcomas NOS, whereas MT-9 cells, which can develop typical MFHs, have more differentiated stem cell nature with greater multipotential differentiation. In MFHs, collectively, MT-8 and MT-9 cells are regarded as “tumor stem cells” and “tumor precursors” in the stem cell lineage, respectively, according to the concept of “cancer stem cell theory”.

Parotid Gland Nodular Fasciitis: A Clinicopathologic Series of 12 Cases with a Review of 18 Cases from the Literature.

Nodular fasciitis (NF), very uncommon in the parotid gland, is a benign myofibroblastic proliferation that may be mistaken for other neoplastic proliferations. The mass-like clinical presentation and histologic features result in frequent misclassification, resulting in inappropriate clinical management. There are only a few reported cases in the English literature. Cases within the files of the authors' institutions (retrospective) confined to the parotid gland were compared to cases reported in the English literature (Medline 1966-2014). The patients included five females and seven males, aged 11-70 years (mean 45.2 years). All patients presented with a mass lesion, present on average 1.9 months, without a documented history of trauma. The lesions were 0.7-5.2 cm (mean 2.2 cm). Seven patients had fine needle aspiration. The majority of the lesions were circumscribed (n = 9), composed of spindle-shaped to stellate myofibroblasts (MF) arranged in a storiform growth pattern, juxtaposed to hypocellular myxoid tissue-culture-like areas with extravasation of erythrocytes. Dense, keloid-like collagen (n = 7) and occasional giant cells were seen (n = 6). Mitotic figures (without atypical forms) were readily identifiable (mean 4/10 HPFs). By immunohistochemical staining, the MF were reactive with vimentin, actins, and calponin, while the histiocytes were reactive with CD68. All patients had surgical excision. One patient developed local recurrence (12 months later). All were alive and disease free at last follow-up, with a mean 133 months of follow-up. The principle differential diagnoses include fibrosarcoma, fibromatosis, pleomorphic adenoma, myoepithelioma, neurofibroma, schwannoma, solitary fibrous tumor, leiomyoma, fibrous histiocytoma and myxoma. NF of the parotid gland occurs in middle-aged patients who present with a mass (mean 2.2 cm) in the parotid gland of short duration (1.9 months). FNA misinterpretation frequently leads to excision. Separation from myoepithelial and mesenchymal lesions affecting the parotid gland results in appropriate management.

Primary Myoepithelioma of Bone

The clinical and pathologic features of 8 primary myoepitheliomas of bone were analyzed. There were 5 female and 3 male patients who ranged in age from 16 to 49 (mean, 33.5) years. Three tumors arose in the ilium, 2 in the tibia, and 1 each in the maxilla, sacrum, and L1 vertebral body. Microscopically, the tumors had a solid, lobulated, reticular, or storiform growth pattern and were predominantly composed of spindle-shaped cells arranged in intersecting fascicles with eosinophilic cytoplasm. The round to polygonal epithelioid cells were arranged randomly or formed small clusters and contained variable amounts of eosinophilic or clear cytoplasm. Immunohistochemically, all the tumors were positive for vimentin and S100 protein, and 7 were positive for epithelial membrane antigen. No tumors were positive for keratin (AE1.3/CAM5.2). Smooth muscle actin was positive in 3 tumors and negative in 4, whereas desmin was negative in all 7 tumors tested. Nuclear staining for p63 was negative in 3 tested tumors. Staining for GFAP and CD34 was performed on 4 and 5 tumors, respectively, and all showed no expression. Fluorescence in situ hybridization for EWSR1 rearrangement was performed in 7 tumors. Five tumors (71%) showed the presence of EWSR1 gene rearrangement, and 2 were negative. Cytogenetic studies conducted on 1 tumor showed 46,XY,t(1;22)(q21;q12) associated with EWSR1-PBX1 fusion. Surgical procedures included curettage in 3 patients, resection in 3 patients, and 2 patients only had an open biopsy. Follow-up information was available for 4 patients; all remain free of disease with no recurrence. Although experience with primary myoepithelioma of bone is limited, histologically, banal tumors appear to behave in a benign manner, and conservative surgery appears to be sufficient treatment. Immunohistochemical and molecular analyses are helpful in their accurate identification.

Pleomorphic Dermal Sarcoma

The behavior of atypical fibroxanthoma is benign, if strict diagnostic criteria are applied. Tumors with similar pathologic features but deep subcutaneous invasion, necrosis, and/or lymphovascular or perineural invasion are thought to be associated with adverse outcome and are better regarded as pleomorphic dermal sarcoma or undifferentiated pleomorphic sarcoma of skin. This tumor group is not well documented in the literature, and its characteristics are only poorly defined. To study the clinical and pathologic spectrum more comprehensively, we retrieved 32 pleomorphic dermal sarcomas from our departmental files. The tumors were large (median: 25 mm) and exclusively presented on sun-damaged skin with a strong predilection for the head. Typically, elderly men were affected (median age: 81 y). Histologically, these often ulcerated tumors were poorly marginated, asymmetrical, and deeply invasive into deep subcutaneous, muscular, and/or fascial tissues. The tumors were cellular and composed of pleomorphic epithelioid cells, atypical spindle cells, and multinucleated tumor giant cells in varying proportions. Mitotic count was brisk and often atypical. Tumor necrosis was observed in 53%, lymphovascular invasion in 26%, and perineural infiltration in 29%. The majority of tumors showed a predominance of atypical spindle cells in a fascicular arrangement. A sheet-like growth of pleomorphic epithelioid cells or mixed spindle and epithelioid cell features were less frequently observed. Myxoid and keloidal change, a desmoplastic stromal response, pseudoangiomatous and storiform growth patterns, and admixed osteoclast-like giant cells were additional morphologic features in some cases. No immunoreactivity was noted for multiple cytokeratins, S100, HMB-45, desmin, and CD34. Smooth muscle actin was expressed in 70%, CD31 in 48%, epithelial membrane antigen in 16%, Melan A in 6%, and p63 in 1 case. CD10 was expressed in all cases stained. Follow-up (available for 29 patients; median: 24 mo) showed local recurrence in 28% and a metastatic rate of 10%, mainly in the skin. Progressive metastatic disease was observed in 2 patients. Remission was achieved in 1 patient using systemic chemotherapy. The second patient died in the setting of advanced-stage non-Hodgkin lymphoma. No disease-related mortality was noted. Our data underscore the importance of recognizing adverse histologic features in tumors otherwise resembling atypical fibroxanthoma. Deep subcutaneous invasion, tumor necrosis, and perineural and/or lymphovascular invasion confers at least low-grade malignant potential.

Extraneural Sclerosing Perineurioma of the Buccal Mucosa: A Case Report and Clinicopathologic Review

The perineurioma is an infrequently encountered benign peripheral nerve sheath tumor composed of a clonal proliferation of perineurial cells. Rare cases of perineurioma have been reported in the oral cavity. An extraneural sclerosing perineurioma arising in the buccal mucosa of a 17-year-old male is presented. Histopathologically, the tumor is composed of a well circumscribed nodular proliferation of spindle cells arranged in a storiform growth pattern, in some areas subtly arranged around vascular channels. The tumor cells reveal positive immunostaining for epithelial membrane antigen (EMA), collagen type IV and vimentin, and negative immunostaining for S-100 protein, consistent with a perineurial origin. To the best of our knowledge, this case represents the first report of an extraneural sclerosing perineurioma involving the oral cavity.

TP53Mutation Analysis of Malignant Peripheral Nerve Sheath Tumors

Mutations in TP53 underlie the development of malignant peripheral nerve sheath tumors (MPNSTs) in animal models, but there is controversy regarding the extent of TP53 mutations in human MPNSTs. We assessed the TP53 mutation frequency in 145 consecutive cases from our department over 36 years; 88 cases were histologically confirmed as MPNSTs, and corresponding clinical data were reviewed. Mutation analysis of TP53 Exons 4 to 9 on DNA from formalin-fixed, paraffin-embedded specimens was performed by bidirectional DNA sequencing. Tumors were localized in the extremities (n = 34), trunk (n = 34), or head and neck (n = 20). A minority of patients (n = 26, 30%) had neurofibromatosis type 1 (NF1); in these patients, the diagnosis of MPNST was made at younger ages (33 [SD, 3.6] years vs 49 [SD, 2.9] years in NF1 vs non-NF1; p = 0.003). High p53 protein expression was detected in 18 (21%) of 86 cases by immunohistochemistry. TP53 mutations were detected in 17 (24%) of 72 evaluable tumors, of which 36% were from NF1 patients. TP53 mutation and strong p53 immunostaining were positively correlated (p = 0.002); high proliferation indices correlated with cellular epithelioid and storiform growth patterns. These results indicate that TP53 mutations are relatively rare in human MPNST and that they are not positively correlated with the presence of NF1.

Primary rhabdomyosarcoma of the sacrum: a case report and review of the literature

We describe herein a rare case of primary rhabdomyosarcoma (RMS) occurring in the sacrum. A 16-year-old woman presented with a 2-month history of pain in bilateral buttocks and posterior thighs. Computed tomography showed a primary tumor with bone destruction in the 2nd sacral vertebra and invasion to the 1st to 3rd vertebrae and retroperitoneal space. Histological examination of the tumor showed proliferation of spindle-shaped cells intermingled with rhabdomyoblasts in a fascicular and storiform growth pattern. Tumor cells showed immunoreactivity for vimentin, desmin, muscle-specific actin, sarcomeric actin, alpha-smooth muscle actin and CD99, and partial immunoreactivity for myoD1, myf-4, myogenin and myoglobin. Reverse transcription polymerase chain reaction demonstrated expression of myoD1. On the basis of the aforementioned findings, a poorly differentiated spindle cell variant of embryonal RMS was diagnosed. The patient underwent combined therapy with chemotherapy and radiotherapy, but died 17 months after incisional biopsy. The present case is instructive in differential diagnosis of primary bone tumors, and the possibility of skeletal RMS needs to be considered.

EBV-Associated Follicular Dendritic Cell Tumor of the Spleen.

Epstein-Barr virus (EBV) expressing follicular dendritic cell proliferations in the spleen is an extremely rare but distinct variant of follicular dendritic cell tumor (FDCT). This neoplasm typically presents as an intra-abdominal mass with a predilection to involve spleen or liver with histologic features reminiscent of inflammatory pseudotumor (IP). However, in contrast to IP, this distinct FDCT consistently is associated with EBV. A subset of splenic tumors previously reported as examples of IP or inflammatory myofibroblastic tumor represent EBV-associated FDCT retrospectively. Despite morphologic similarity with IP, at least focal proliferation of follicular dendritic cells can often be demonstrated using follicular dendritic cell markers. Based on the limited published cases (Cheuk W, et al: Am J Surg Pathol , 2001; 25:721–731), these proliferations can recur and/or metastasize but in contrast to classical intra-abdominal FDCT, their clinical behavior remains indolent. We report a case of 37-year-old gentleman who presented with a four month history of left-sided abdominal and flank pain, 8 lbs weight loss over a month, and on and off night sweats during the past two years. Initial blood tests including a CBC, LDH, electrolytes, renal and liver function were all within normal limits. CT scan of abdomen and pelvis revealed a 5.5 cm in diameter solitary splenic mass with cystic and solid components (Figure 1). There was no intra-abdominal or retroperitoneal lymphadenopathy. Hepatitis panel, EBV DNA PCR and also HIV serology were all negative. The patient underwent splenectomy due to clinical impression of a lymphoproliferative disorder. Pathology: The spleen weighed 237 grams and contained a solitary, 6 cm in greatest dimension, well circumscribed tumor. Histologically, the tumor was composed of a mixed population of small lymphocytes, histiocytes, plasma cells, and variable numbers of large oval to spindle cells. The spindle cells in some foci exhibited a storiform growth pattern. Neither overt cytologic atypia nor significant increased mitotic activity was present. Flow cytometric analysis revealed no monoclonal B-cell population or abnormal T-cell proliferation. Cytogenetic analysis revealed normal 46,XY karyotype in 20 metaphases. By paraffin immunohistochemistry, the spindled cells were positive for follicular dendritic cell markers CD21, CD35 and CD23. In situ hybridization using EBV RNA (EBER) probes revealed abundant EBV RNA transcripts in the nuclei of spindled and large oval cells (Figure 2). The spindle cells were negative for S-100 and ALK protein. The systemic symptoms resolved following splenectomy with no additional treatment. Six months after splenectomy, the patient remains asymptomatic and disease free at last clinical follow up. [Display omitted] [Display omitted]

Establishment and characterization of two distinct malignant mesothelioma cell lines with common clonal origin

We describe two newly established malignant mesothelioma (MM) cell lines derived from a pleural effusion of a male. One cell line, designated as MM-Z03E, reveals an epithelioid cobblestone morphology, while the second one, designated as MM-Z03S and subcloned after in vivo selection, exhibits a sarcomatoid storiform growth pattern. Both cell lines showed the immunologic profile characteristic for MM (i.e., expression of cytokeratin, CK18, calretinin, and vimentin in both phenotypes). Cytogenetics, multicolor fluorescence in situ hybridization, comparative genomic hybridization, and oligonucleotide array CGH were performed on both cell lines. Aberrations shared by both cell lines included chromosomal losses of 1q34∼qter, 4, 9p, 10p, 13, 14, 16q, 18, and 22, as well as a complex structural aberration involving chromosome 17. Aberrations exclusive to MM-Z03E included gains of 3q11q27 and 5p, while gain of 9q and losses of 3q27qter, 11q, and 18 in MM-Z03S were exclusive to MM-Z03E. Both cell lines were able to develop solid transplant tumors in nude mice within 16 weeks, and immunophenotyping of tumor xenografts revealed an overall retained expression profile of the markers used. Remarkably, one xenograft from MM-Z03E revealed overexpression of p53 and widely invasive growth. In conclusion, both cell lines are useful in vivo and in vitro model systems to study the underlying genetic mechanisms of biphasic differentiation in MM, which can be of certain value considering the increasing relevance of assessing MM tumor biology for the clinical management of this disease.

Benign hybrid perineurioma-schwannoma in the colon. A case report

A 48-year-old man of Haitian descent presented with progressive constipation, hematochezia, and weight loss. Colonoscopy and computed tomography scan revealed an obstructing colonic mass, causing intussusception and pneumatosis of the descending/upper sigmoid colon and necessitating an emergency left hemicolectomy. Gross examination revealed a 4.9-cm obstructing mass in the sigmoid colon extending through the muscularis propria. Histologically, the lesional cells were bland, spindled, with tapered and often wavy nuclei set in a loose fibromyxoid stroma. Focally, the lesional cells displayed whorling or storiform growth pattern mixed with spindle wavy cells. In many areas, the cells had bipolar cytoplasmic processes. Immunohistochemistry revealed patchy positivity for epithelial membrane antigen, CD34, vimentin, diffuse positivity for S-100, and negativity for CD117, cytokeratin (AE1/AE3), ALK1, desmin, smooth muscle actin, neuronal nuclei antigen (NeuN), and neurofilament protein. The morphology and immunohistochemical findings were consistent with hybrid perineurioma-schwannoma. Electron microscopic examination revealed the characteristic features of perineuriomal and schwannomatous differentiation. Based upon the histopathology, immunophenotype, and ultrastructure, this tumor was classified as a benign hybrid perineurioma-schwannoma, a counterpart to the tumor described in the soft tissue. This is the first case report of hybrid perineurioma-schwannoma in the colon.

Interdigitating dendritic cell tumor with breast and cervical lymph-node involvement: a case report and review of the literature

Interdigitating dendritic cell tumor (IDCT) is an extremely rare malignancy. It occurs primarily in lymph nodes, but extranodal involvement has also been reported. A 38-year-old woman with IDCT with breast and cervical lymph-node involvement is reported in this paper. To our knowledge, this is the first case of IDCT originating from the breast. In the breast and lymph node, the tumor displayed diffuse sheets, fascicles and storiform growth pattern. It was composed of oval to spindle cells with pale to eosinophilic cytoplasm, ill-defined cell outlines, oval nuclei with vesicular chromatin and prominent eosinophilic nucleoli. Mitotic activity was three per ten high-power fields. The neoplastic cells were intermingled with small mature lymphocytes and plasma cells. Immunohistochemical studies showed that the tumor cells were strongly and diffusely positive for vimentin, CD68, S-100 protein, CD45/leukocyte common antigen and fascin and focally positive for lysozyme, alpha-1 antitrypsin and CD4. Ki-67 labeling index was 10%. The patient was treated with combined therapeutic approaches, including surgery, radiotherapy and chemotherapy. IDCT has the potential for an aggressive clinical course. However, 32 months after the initial diagnosis, the patient is still alive and being followed with a stable tumor burden.

Angioarchitecture of tumors induced by two different cloned cell lines established from a transplantable rat malignant fibrous histiocytoma.

Angiogenesis, a biologic process whereby endothelial cells divide and migrate to form new blood vessels, is a key step in tumor growth, invasion, and metastasis. In the present study, we investigated the differences in angioarchitecture between two different tumors induced by cloned cell lines (MT-8 and MT-9), derived from a transplantable rat malignant fibrous histiocytoma, by scanning electron microscopy of vascular corrosion casts. During a 3-week observation period after implantation, the growth of MT-8 tumors appeared to be faster than that of MT-9 tumors. Histologically, MT-8 tumors were of the uniformly undifferentiated sarcoma type arranged in characteristic organoid structures, and MT-9 tumors showed a storiform growth pattern. In MT-8 tumors, neovascularization occurred by sprouting at postimplantation (PI) week 1, and the newly formed capillaries gradually became more tortuous. In MT-9 tumors, at PI week 1, the corrosion casts of newly formed capillaries mainly showed a wavy course but no finger-like outgrowths of capillaries were seen. At PI weeks 2 and 3, the sprouting was seen specifically in MT-9 tumors, forming basket-like structures and glomeruloid structures of capillaries. These results indicate that angiogenesis or angioarchitecture of MT-8 tumors is different from that of MT-9 tumors, depending on the differences in their tumor histology and by the features like absence or presence of basket-like structures and glomeruloid structures of capillaries.

Cutaneous rosai-dorfman disease is a distinct clinical entity.

Rosai-Dorfman disease (RDD) is a rare but distinctive clinicopathologic entity of unknown etiology affecting lymph nodes as well as extranodal sites. Although cutaneous involvement in RDD is common, purely cutaneous disease is rare and not well documented. We report 22 patients with cutaneous and superficial subcutaneous RDD. The lesions presented as papules and nodules, often with discoloration (9/22) and frequent multifocality (13/22), without predilection for a specific site of the body. Age distribution was wide and ranged from 15 to 68 years, with a median of 43.5 years. Of the 17 patients for whom information on racial background was available, 7 were Asian, 8 were white, and 2 were black, with a marked female predominance (2:1). The lesions resolved in 6 of 13 patients for whom follow-up data were available, regardless of the treatment given. Lesions persisted or recurred in 7 patients. Histologically, the lesions are invariably characterized by a proliferation of polygonal S100-positive histiocytes showing emperipolesis and a mixed inflammatory infiltrate. This study characterizes the histologic spectrum of cutaneous RDD in regard to variation in the numbers of typical S100-positive histiocytes and emperipolesis, variation in the quality and quantity of the inflammatory response, and the degree of stromal fibrosis, which resulted in a strikingly storiform growth pattern in six lesions and a lobulated pattern in two lesions. Whereas the clinical as well as histologic appearance of the cutaneous and subcutaneous lesions in the purely extranodal forms of RDD is indistinguishable from that of systemic RDD, this study emphasizes that purely cutaneous RDD is a distinct clinical entity in regard to its epidemiology and remains localized to the skin even with long-term follow-up. Patients with purely cutaneous RDD are of an older age at onset of disease (median = 43.5 years), with a reversed male/female ratio. There are no significant systemic extracutaneous or serologic manifestations. Whereas systemic RDD is commonly seen in blacks and only rarely reported in Orientals, the majority of the patients in this series with purely cutaneous RDD are Asians and whites.

Intrarenal Solitary Fibrous Tumor of the Kidney

Solitary fibrous tumor (SFT) is a neoplasm that can occur in the urogenital tract, and is also reported occurring in the spermatic cord, seminal vesicles, urinary bladder, prostate, and kidney. Furthermore, it is most important to consider its existence in the kidney, because it is usually diagnosed as renal cell carcinoma pre-operatively. To our knowledge, only 10 cases of SFT have been reported in the kidney to date. We report the clinico-pathological features of an intrarenal SFT occurring in a 31-year-old woman. The tumor, measuring 8.6 cm in its greatest diameter, completely replaced the cortex and the medulla of the middle region of the right kidney, compressing the pelvis. Radiological imaging was consistent with a renal cell carcinoma. Histologically, the tumor was composed of a proliferation of bland-looking vimentin+, CD34+, bcl2+ and CD99+ spindle cells exhibiting a haphazard to storiform growth pattern, pushing borders, and a low mitotic rate (2 mitoses x 10 HPF). We placed emphasis on the differential diagnostic problems, i.e., its differentiation from other primary monomorphous benign and malignant spindle cell tumors of the kidney, such as fibroma, benign fibrous histiocytoma, hemangiopericytoma, inflammatory myofibroblastic (pseudo-)tumor, leiomyoma, angiomyolipoma with predominant spindle cell smooth muscle component, benign peripheral nerve sheath tumors, renal mixed epithelial/stromal tumors, adult type mesoblastic nephroma, fibrous type monophasic synovial sarcoma, malignant peripheral nerve sheath tumors, fibrosarcoma, and low-grade fibromyxoid sarcoma.