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Brain Pathology (Zurich, Switzerland) Mar 2020Desmoplastic small round cell tumors (DSRCTs) are highly aggressive sarcomas that most commonly occur intra-abdominally, and are defined by EWSR1-WT1 gene fusion....
Desmoplastic small round cell tumors (DSRCTs) are highly aggressive sarcomas that most commonly occur intra-abdominally, and are defined by EWSR1-WT1 gene fusion. Intracranial DSRCTs are exceptionally rare with only seven previously reported fusion-positive cases. Herein, we evaluate the clinical, morphologic, immunohistochemical and molecular features of five additional examples. All patients were male (age range 6-25 years; median 11 years), with four tumors located supratentorially and one within the posterior fossa. The histologic features were highly variable including small cell, embryonal, clear cell, rhabdoid, anaplastic and glioma-like appearances. A prominent desmoplastic stroma was seen in only two cases. The mitotic index ranged from <1 to 12/10 HPF (median 5). While all tumors showed strong desmin positivity, epithelial markers such as EMA, CAM 5.2 and other keratins were strongly positive in only one, focally positive in two and negative in two cases. EWSR1-WT1 gene fusion was present in all cases, with accompanying mutations in the TERT promoter or STAG2 gene in individual cases. Given the significant histologic diversity, in the absence of genetic evaluation these cases could easily be misinterpreted as other entities. Desmin immunostaining is a useful initial screening method for consideration of a DSRCT diagnosis, prompting confirmatory molecular testing. Demonstrating the presence of an EWSR1-WT1 fusion provides a definitive diagnosis of DSRCT. Genome-wide methylation profiles of intracranial DSRCTs matched those of extracranial DSRCTs. Thus, despite the occasionally unusual histologic features and immunoprofile, intracranial DSRCTs likely represent a similar, if not the same, entity as their soft tissue counterpart based on the shared fusion and methylation profiles.
Topics: Adolescent; Adult; Biomarkers, Tumor; Brain Neoplasms; Child; Desmoplastic Small Round Cell Tumor; Humans; Male; Young Adult
PubMed: 31837177
DOI: 10.1111/bpa.12809 -
Pathology Mar 2023Desmoplastic melanoma is a subtype of melanoma characterised by amelanotic fusiform melanocytes dispersed in a collagenous stroma. Cell-poor and fibrous stroma-rich...
Desmoplastic melanoma is a subtype of melanoma characterised by amelanotic fusiform melanocytes dispersed in a collagenous stroma. Cell-poor and fibrous stroma-rich 'pure' variants have been distinguished from 'mixed' variants with areas of higher cell density and/or less desmoplastic stroma. This distinction is relevant because patients whose tumours display a pure phenotype have a lower risk for regional lymph node metastasis and distant recurrence. However, little is known about interobserver agreement among pathologists in the subclassification of desmoplastic melanoma. To address this issue, we conducted a study in which eleven dermatopathologists independently evaluated whole slide scanned images of excisions from 30 desmoplastic melanomas. The participating pathologists were asked to classify the tumours as pure or mixed. They were also asked to record the presence or absence of neurotropism and angiotropism. We found substantial interobserver agreement between the 11 dermatopathologists in the classification of tumours as pure versus mixed desmoplastic melanoma (kappa=0.64; p<0.0001). There was fair agreement between the 11 dermatopathologists in the evaluation of presence versus absence of neurotropism (kappa=0.26; p<0.0001), and slight agreement in the assessment of angiotropism (kappa=0.13; p<0.0001). The level of concordance in the subclassification of desmoplastic melanomas is encouraging for the acceptance of this prognostic parameter in the real-world practice of melanoma pathology.
Topics: Humans; Skin Neoplasms; Observer Variation; Melanoma; Prognosis
PubMed: 36653238
DOI: 10.1016/j.pathol.2022.12.347 -
Cureus May 2024Primary orbital melanoma and metastatic cutaneous melanoma of the orbit are extremely rare. Desmoplastic melanoma (DM) is an infrequent variant of melanoma that can...
Primary orbital melanoma and metastatic cutaneous melanoma of the orbit are extremely rare. Desmoplastic melanoma (DM) is an infrequent variant of melanoma that can extend from a superficial location into deep tissues by neurotropic mechanisms. A 78-year-old male was referred to us with a periocular mixed malignant melanoma (spindle cell melanoma with desmoplastic reaction) in his left lower eyelid with uncontrollable disease (orbital and inferior orbital rim invasion) despite treatment. The surgical technique consisted of an extended orbital exenteration, maxillectomy, and ethmoidectomy, with a 2 cm macroscopic surgical margin. We performed a delayed socket reconstruction with a temporalis muscle flap using a transorbital approach. The patient remained disease-free for 1.5 years with a good quality of life since exenteration surgery. At this time, he presented a recurrence in the area of the malar scar with a new orbital invasion, and finally, he died due to mediastinal, pleural, and pulmonary metastasis. The treatment of a cutaneous melanoma arising in the periocular region is a challenging reconstructive problem and it may compromise the globe and visual function.
PubMed: 38887344
DOI: 10.7759/cureus.60541 -
Journal of Medical Case Reports Nov 2022Down's syndrome is the most common chromosomal abnormality in humans. It has been associated with central nervous system tumors such as primary acute lymphoblastic...
BACKGROUND
Down's syndrome is the most common chromosomal abnormality in humans. It has been associated with central nervous system tumors such as primary acute lymphoblastic leukemia and germinomas, but desmoplastic infantile astrocytoma has not yet been reported with Down's syndrome. Desmoplastic infantile astrocytoma is a rare intracranial tumor that mostly occurs in the first 2 years of life. It usually presents as a large, aggressive tumor with both solid and cystic components. Genetically, it has been linked to the BRAF V600E mutation. Despite the rapid growth pattern, it usually has a favorable prognosis after neurosurgical excision. The presence of this extremely rare, genetically linked tumor, and its combination with Down's syndrome, the most common human genetic defect, makes this a very novel clinical presentation. It also raises a very research-worthy question of an undiscovered link between these two genetic disorders.
CASE PRESENTATION
In this case, we report a 1-year-old Pakistani origin male child with Down's syndrome, who presented with progressive macrocephaly and developmental regression over the last 2 months. He was unable to sit by himself, and had lost his handgrip bilaterally. Down's Syndrome was diagnosed soon after birth, based on typical facial features and presence of palmar crease, and later confirmed karyotypically for Trisomy 21. Upon presentation, initial blood tests did not show any abnormality. Magnetic resonance imaging of the brain was done, and showed a mixed intensity cystic mass with solid dural component posteriorly in the right parieto temporo occipital region. Craniotomy was performed, and about 85% of the tumor mass was excised. Histological examination and immunochemistry confirmed the suspected radiological diagnosis of desmoplastic infantile astrocytoma. After surgical excision, our patient gradually reacquired his previously regressed developmental milestones. Unfortunately, the remaining mass, which could not be excised due to its attachment to the highly vascular dura mater, showed regrowth on repeat brain magnetic resonance imaging. As his parents did not consent to further surgery, chemotherapy was offered as the next treatment option to prevent tumor regrowth.
CONCLUSIONS
This case report highlights the need for more case data and research to understand desmoplastic infantile astrocytoma, and their genetic correlation with Down's syndrome. From a clinical standpoint, since desmoplastic infantile astrocytoma has a good postresection prognosis in a majority of early-diagnosed clinical cases, pediatricians, radiologists, and pathologists should consider desmoplastic infantile astrocytoma in their initial differential diagnosis in Down's syndrome patients with macrocephaly and developmental regression during the first 2 years of life.
Topics: Humans; Infant; Male; Astrocytoma; Brain Neoplasms; Down Syndrome; Ganglioglioma; Hand Strength; Hyperplasia; Magnetic Resonance Imaging; Megalencephaly
PubMed: 36333774
DOI: 10.1186/s13256-022-03615-0 -
International Journal of Surgery Case... 2011Desmoplastic small round cell tumor is a rare malignancy with poor prognosis that predominantly affects young males. Its etiopathogenesis is still unknown and diagnosis...
INTRODUCTION
Desmoplastic small round cell tumor is a rare malignancy with poor prognosis that predominantly affects young males. Its etiopathogenesis is still unknown and diagnosis can be achieved only by immunohistochemistry and cytogenetic studies. Due to our limited knowledge of the pathologic and clinical nature of this disease, there is no clear consensus regarding the optimal therapeutic procedures for treating this neoplasm. A high degree of care and improvements in diagnostic capabilities are required in order to identify this entity and avoid misdiagnosis.
CASE PRESENTATION
We report a new case of a 29-year-old male who proceeded to our Emergency Department complaining about non-specific abdominal pain. Physical examination revealed no abnormalities except for a palpable mass in the lower abdomen and a diffuse abdominal pain. Computed Tomography scan showed enlarged paraortic and mesenteric lymphadenopathy, thickness of the small bowel wall and dispersed masses intraperitoneally. He underwent an exploratory laparotomy and the resultant biopsy revealed desmoplastic small round cell tumor.
DISCUSSION
Diagnosis of desmoplastic small round cell tumor can easily be missed because it presents with few early warning symptoms and signs, while the routine blood tests are within normal limits.
CONCLUSION
A high degree of suspicion, a thorough physical examination, a full imaging check and an aggressive therapeutic approach are required in order to identify this disease and fight for a better quality of life for these patients. In addition we make a review of the literature in an effort to clarify the epidemiological, clinical and pathological aspects of this entity.
PubMed: 22096758
DOI: 10.1016/j.ijscr.2011.08.013 -
Annals of Surgical Oncology Jan 2020Desmoplastic small round cell tumor (DSRCT) is a rare intra-abdominal soft tissue sarcoma affecting adolescents and young adults. Cytoreduction, hyperthermic...
BACKGROUND
Desmoplastic small round cell tumor (DSRCT) is a rare intra-abdominal soft tissue sarcoma affecting adolescents and young adults. Cytoreduction, hyperthermic intraperitoneal chemotherapy (CRS/HIPEC), and adjuvant radiotherapy may improve local control. We review our experience with patients who undergo CRS/HIPEC and adjuvant radiotherapy for DSRCT.
METHODS
A retrospective review was performed for patients with DSRCT from 2013 to 2017 who underwent CRS/HIPEC. Clinicopathologic, operative, and outcome data were reviewed.
RESULTS
Ten CRS/HIPEC procedures were performed for nine patients (7 males, 6 Caucasian, median age 19 years (range 10-24)). Four patients presented with extra-abdominal disease; five had liver involvement. The median peritoneal cancer index was 16 (range 5-20). All received neoadjuvant chemotherapy. CCR 0/1 resection was possible in nine patients. Major complications occurred in four with no operative mortalities. All received adjuvant chemotherapy, seven received radiation therapy, and three received stem-cell transplant. All but one patient recurred after treatment. The median recurrence-free and overall survival (OS) were 12 and 45 months (95% confidence interval 35.1-54.9) respectively, with a 3-year OS of 55%. Long-term parenteral nutrition was required in eight for a median of 261 days (range 37-997). Clinically significant long-term complications requiring further surgery included gastroparesis (N = 1), small bowel obstruction (N = 3) and hemorrhagic cystitis (N = 2).
CONCLUSIONS
Multimodal therapy for DSRCT consisting of multiagent neoadjuvant chemotherapy, CRS/HIPEC, adjuvant chemotherapy, and radiation therapy is associated with potential cumulative toxicity. Recurrence after resection is common. Prolonged parenteral nutrition may be necessary, and late gastrointestinal and genitourinary complications may require additional treatment.
Topics: Adolescent; Antineoplastic Agents; Chemotherapy, Adjuvant; Child; Combined Modality Therapy; Cytoreduction Surgical Procedures; Desmoplastic Small Round Cell Tumor; Female; Follow-Up Studies; Humans; Hyperthermia, Induced; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Peritoneal Neoplasms; Postoperative Complications; Retrospective Studies; Survival Rate; Young Adult
PubMed: 30963398
DOI: 10.1245/s10434-019-07339-2 -
BMC Cancer Aug 2022The histopathological growth patterns (HGPs) are a prognostic and predictive biomarker in colorectal cancer liver metastasis (CRLM). This study evaluates the...
BACKGROUND
The histopathological growth patterns (HGPs) are a prognostic and predictive biomarker in colorectal cancer liver metastasis (CRLM). This study evaluates the relationship between the HGP and primary colorectal cancer (CRC) histopathology.
METHODS
A total of 183 treatment-naive patients with resected CRC and CRLM were included. Thirteen CRC histopathology markers were determined and compared between the desmoplastic and non-desmoplastic HGP; tumour sidedness, pT&pN stage, tumour grade, tumour deposits, perineural- (lympho-)vascular- and extramural venous invasion, peritumoural budding, stroma type, CRC growth pattern, Crohn's-like lymphoid reaction, and tumour-infiltrating lymphocyte (TIL) density. Logistic regression analysis was performed using both CRC and CRLM characteristics.
RESULTS
Unfavourable CRC histopathology was more frequent in non-desmoplastic CRLM for all markers evaluated, and significantly so for a lower TIL density, absent Crohn's-like lymphoid reaction, and a "non-mature" stroma (all p < 0.03). The cumulative prevalence of unfavourable CRC histopathology was significantly higher in patients with non-desmoplastic compared to desmoplastic CRLM, with a median (IQR) of 4 (3-6) vs 2 (1-3.5) unfavourable characteristics observed, respectively (p < 0.001). Multivariable regression with 9 CRC histopathology markers and 2 CRLM characteristics achieved good discriminatory performance (AUC = 0.83).
CONCLUSIONS
The results of this study associates primary CRC histopathology with the HGP of corresponding liver metastases.
Topics: Cell Proliferation; Colorectal Neoplasms; Humans; Liver Neoplasms; Lymphocytes, Tumor-Infiltrating; Prognosis
PubMed: 35996090
DOI: 10.1186/s12885-022-09994-3 -
Journal of Bone Oncology Feb 2021Desmoplastic fibroma (DF) is an intraosseous counterpart of desmoid-type soft tissue fibromatosis. It is most frequently seen in the jawbones. The clinical and...
Desmoplastic fibroma (DF) is an intraosseous counterpart of desmoid-type soft tissue fibromatosis. It is most frequently seen in the jawbones. The clinical and radiological features of the present cases were nonspecific. The accumulation of beta-catenin in the nuclei of neoplastic cells which is a diagnostic feature of desmoid-type soft tissue fibromatosis could not be detectED in the present DF series. The aim of this study is to report a series of 22 cases of DF involving either mandible or maxilla. A retrospective evaluation of desmoplastic fibroma and beta-catenin, smooth muscle actin, nestin, cyclin D1 immunostaining's patterns. Most of the DF cases expressed only cytoplasmic beta-catenin immunostainings. We suggest that nuclear beta-catenin staining may not be used as a corroborating the diagnosis of DF. Immunohistochemical staining difference of jaw bone desmoplastic fibromas from other soft tissue and bone lesions may be related to the origination of jaw bone from The neural crest. Strong nestin and cyclin D1 positivity in our series supported this. A combined clinical, radiological, and histopathological analysis of the DF cases is essential in the diagnosis and management.
PubMed: 33204607
DOI: 10.1016/j.jbo.2020.100333 -
Oncology Letters May 2013Desmoplastic small round cell tumor (DSRCT) is an extremely rare and aggressive neoplasm, which mainly affects young males and generally presents as a widely...
Desmoplastic small round cell tumor (DSRCT) is an extremely rare and aggressive neoplasm, which mainly affects young males and generally presents as a widely disseminated tumor within the peritoneal cavity. Due to the rarity of the tumor, its younger and overall healthier patient population (compared with other tumor types) and the fact that it lacks definitive histological and immunohistological features, the diagnosis of DSRCT may be frequently delayed or the tumor may be entirely misdiagnosed as a different type of abdominal sarcoma. The present study aimed to rectify the lack of models that exist for this rare neoplasm, through the development of several DSRCT tissue cultures and xenograft lines. Samples were received from surgeries and biopsies from patients worldwide and were immediately processed for xenograft development in nude mice. Tumor tissues were minced and fragments were injected into the dorsal flanks of nude mice. Of the 14 samples received, nine were established into xenograft lines and five into tissue culture lines. Xenografts displayed the microscopic histology of their parent tumors and demonstrated two different growth rates among the established xenograft lines. Overall, the establishment of these xenograft and tissue culture lines provides researchers with tools to evaluate DSRCT responses to chemotherapy and to investigate DSRCT-specific signaling pathways or mechanisms.
PubMed: 23759995
DOI: 10.3892/ol.2013.1265 -
International Journal of Molecular... Nov 2020Kinase drug discovery represents an active area of therapeutic research, with previous pharmaceutical success improving patient outcomes across a wide variety of human... (Review)
Review
Kinase drug discovery represents an active area of therapeutic research, with previous pharmaceutical success improving patient outcomes across a wide variety of human diseases. In pancreatic ductal adenocarcinoma (PDAC), innovative pharmaceutical strategies such as kinase targeting have been unable to appreciably increase patient survival. This may be due, in part, to unchecked desmoplastic reactions to pancreatic tumors. Desmoplastic stroma enhances tumor development and progression while simultaneously restricting drug delivery to the tumor cells it protects. Emerging evidence indicates that many of the pathologic fibrotic processes directly or indirectly supporting desmoplasia may be driven by targetable protein tyrosine kinases such as Fyn-related kinase (FRK); B lymphoid kinase (BLK); hemopoietic cell kinase (HCK); ABL proto-oncogene 2 kinase (ABL2); discoidin domain receptor 1 kinase (DDR1); Lck/Yes-related novel kinase (LYN); ephrin receptor A8 kinase (EPHA8); FYN proto-oncogene kinase (FYN); lymphocyte cell-specific kinase (LCK); tec protein kinase (TEC). Herein, we review literature related to these kinases and posit signaling networks, mechanisms, and biochemical relationships by which this group may contribute to PDAC tumor growth and desmoplasia.
Topics: Adenocarcinoma; Desmoplastic Small Round Cell Tumor; Discoidin Domain Receptor 1; Disease Progression; Humans; Neoplasm Proteins; Pancreatic Neoplasms; Protein-Tyrosine Kinases; Proto-Oncogene Mas; Proto-Oncogene Proteins c-hck; Signal Transduction; src-Family Kinases
PubMed: 33233470
DOI: 10.3390/ijms21228823