Malignant Small Cell Tumor Research Articles

Cytology of desmoplastic small round cell tumor.

Desmoplastic small round cell tumor (DSRCT) is a high-grade malignant tumor that has a predilection for adolescent males and usually affects the abdominal cavity. The cytology literature regarding DSRCT, including aspirates and ascitic fluid, is limited. To the authors' knowledge, findings in ThinPrep slides have not been described previously. Seven cytologic specimens from five patients with histologically confirmed DSRCT were reviewed. Five specimens were fine-needle aspiration biopsies (FNABs), (liver, flank soft tissue, abdomen, and two resected colons [pericolic]) and two specimens were ascitic fluid. Cytologic features were studied in ThinPrep slides and direct smears, which included hematoxylin and eosin, Papanicolaou, and Quik-Dip stains. All specimens showed moderate to high cellularity. The tumor cells were arranged singly and in clusters. The cells demonstrated high nuclear/cytoplasmic ratios, granular chromatin reminiscent of small cell carcinoma, usually inconspicuous nucleoli, smooth to irregular nuclear membranes, and frequent nuclear molding. The cytoplasm was scant to moderate, pale blue, and occasionally vacuolated. Pseudorosettes were observed in six specimens. One ThinPrep slide and the direct smears contained cells with perinuclear, cytoplasmic densities. Stromal fragments were present in the direct smears but were uncommon in ThinPrep. Three specimens were diagnosed as being consistent with DSRCT. Two specimens were diagnosed as malignant small cell tumor. Molecular studies performed on histologic material in four cases confirmed the presence of the diagnostic translocation, t(11;22)(p13;q12). DSRCT may be diagnosed accurately in cytology specimens. Characteristic cytologic features include granular chromatin, smooth to irregular nuclear membranes, nuclear molding, cytoplasmic vacuoles, pseudorosettes, and metachromatic stroma. Cytoplasmic densities may be observed in direct smears and ThinPrep slides.

Merkel Cell (Neuroendocrine) Carcinoma of the Vulva: A Case Report with Immunohistochemical and Ultrastructural Findings and Review of the Literature

A new case of primary Merkel cell carcinoma (MCC) of the vulva is reported and the literature reviewed for noting its clinical presentation, microscopic, immunohistochemical and ultrastructural features, as well as for establishing the role of immunohistochemistry in the ultimate diagnosis of this uncommon and aggressive tumor. The lesion occurred in a 79 year old patient. Histologically, the tumor was composed of intradermal small cells with high mitotic index and frequent apoptosis. The immunohistochemical study showed positivity for wide spectrum and low molecular weight cytokeratins, epithelial membrane antigen, neurofilaments, neuron specific enolase and chromogranin A. Electron microscopy revealed intermediate filaments in a typical globular paranuclear arrangement. The coexpression of cytokeratins (including cytokeratin 20) and neurofilaments, both in typical globular paranuclear arrangement, made possible the diagnosis of MCC, differentiating it from other malignant small cell tumors such as neuroendocrine metastatic carcinoma.

Neurogenic tumors of the mediastinum in children.

Neurogenic tumors of the mediastinum are among the most common mediastinal tumors. They include nerve sheath, autonomic nervous system, and paraganglionic tumors and malignant small cell tumor. Neurogenic tumors arise primarily in the paravertebral sulcus. They are most frequently identified as asymptomatic lesions on routine chest X-rays. The majority of symptoms can be related either to compression of neural elements or other intrathoracic structures or to excess production of biogenic amines. Complete surgical excision performed by a thoracotomy approach offers the best opportunity for cure. In the case of tumors with extension into the spinal canal, a combined thoracic and neurosurgical approach should be performed.

Malignant small cell (Askin) tumor of the thoracopulmonary region originating from the phrenic nerve

Malignant small cell (Askin) tumor of the thoracopulmonary region originating from the phrenic nerve

Primitive neuroectodermal tumor

The primitive neuroectodermal tumor is a rare soft tissue neoplasm occurring in children and young adults. It derives from a carcinogeneic alteration of pluripotent neural crest cells, caused by a balanced reciprocal translocation t(11;22) (q24;q12). Treatment of this undifferentiated, extremely malignant small cell tumor is carried out in compliance with the soft tissue trail (CWS) from the German Society of Pediatric Oncology. Biopsy-proven diagnosis is followed by primary chemotherapy, which in 95% of cases leads to remission, allowing excision of the remainder of the tumor without mutilation and avoidance of intraoperative tumor cell dissemination. After excision, irradiation of the tumor site and two further sequences of chemotherapy are performed. If PNETs of the paravertebral region cause symptoms of paralysis and immediate surgery is required, postoperative chemotherapy, a second-look operation and irradiation are mandatory. Between 1986 and 1994, in cooperation with our pediatric and radiotherapy colleagues, we treated ten patients. In four patients (median age, 14 years) the PNET originated from the chest wall, in six patients from the paravertebral and retroperitoneal region. Five patients died after 20 months on average, while the remaining five patients are in full remission after 31, 46, 50, 51 and 91 months, respectively.

Preresection Chemotherapy Improves Survival for Children With Askin Tumors

To test whether patients with Askin tumor treated with aggressive neoadjuvant chemotherapy have a better clinical outcome. Retrospective case series. Pediatric referral center. All children diagnosed with malignant small-cell tumors of the chest wall (Askin tumor) and treated from 1975 to September 1987 (phase 1, n = 6) and from September 1987 to the present (phase 2, n = 9). Survival as a function of extent of disease and response to therapy as measured by tumor volume, survival, and recurrence. All phase 2 patients had significant reduction of tumor volume and improved survival by Kaplan-Meier estimates compared with phase 1 patients. No phase 1 patients are still alive. Patients with Askin tumor treated with aggressive preresection chemotherapy have smaller tumors to resect and improved survival.

Peripheral neuroectodermal tumor of the chest (Askin tumor) as secondary neoplasm after Hodgkin's disease: A case report

The authors present the case of a 20-year-old woman who developed a peripheral neuroectodermal neoplasm of the thoracopulmonary region (Askin tumor) 7 years after achieving complete remission of stage-IV Hodgkin's disease. The previous treatment had consisted of eight courses of alternating MOPP/ABVD combined with involved-field 20-Gy radiotherapy. The second neoplasm appeared in a nonirradiated area of the chest wall, with erosion of the ribs as shown by sonography and computed tomography. The histological pattern was in accordance with a generic diagnosis of a malignant small cell tumor; the immunostaining positivity of the neoplastic cells for the neuron-specific enolase allowed us to make the diagnosis of a tumor with a neuroectodermal origin. Partial resection of the neoplasm and four courses of chemotherapy including adriamycin, cisplatin, and ifosfamide induced a complete remission, confirmed by surgical restaging. She is alive and well 10 months after the completion of therapy. The clinical, radiological, and microscopic features of this tumor occurring as a secondary neoplasm after Hodgkin's disease are described.

Small round blue cell malignant tumors of soft tissues and bone in adult patients

Small round blue cell malignant tumors of soft tissues and bone in adult patients

Nonpulmonary small cell carcinomas of extragenital origin metastatic to the ovary

Seven small cell carcinomas of extragenital and extrapulmonary origin that metastasized to the ovary are described. The tumors occurred in women who were 21-77 years of age (mean, 49 years) and were discovered at, or close to, the time of presentation. The primary sites were the intestine (three cases), thymus (two cases), and inguinal skin (one case), and in one case it was undetermined. The ovarian tumors, four of which were bilateral, ranged from 1.2 to 25 cm in diameter (mean, 11 cm). Microscopic examination showed typical features of small (oat) cell carcinoma in six cases; one neoplasm resembled a small cell carcinoma of intermediate cell type and contained rare glands. On immunohistochemical examination, six of six tumors stained for cytokeratin, five of five for neuron-specific enolase, two of six for chromogranin, and none of four for vimentin. The primary cutaneous tumor was a Merkel cell carcinoma. The patient with that case died at 8 months. Two patients with intestinal tumors died at 1 and 2 months, and one is free of disease at 4 years after receiving chemotherapy. Both patients with mediastinal tumors received chemotherapy; one died at 11 months and one had brain metastases at 5 months and was lost to follow-up. The final case is recent. The differential diagnoses in these cases include primary ovarian small cell carcinomas of hypercalcemic and pulmonary types and various other small cell malignant tumors metastatic to the ovary. Consideration of a variety of clinical and pathologic features should enable these important distinctions to be made.

Merkel cell carcinoma of the labial mucosa: An immunohistochemical and ultrastructural study with a review of the literature on oral Merkel cell carcinomas

Merkel cell carcinoma is a rare cutaneous neuroendocrine tumor that occurs predominantly in the head and neck region of older patients. An 88-year-old white man had an erythematous, umbilicated tumor on his lower lip, which on histopathologic examination showed solid sheets of infiltrating basaloid round cells with a high mitotic index. Globular, paranuclear immunostaining for low-molecular-weight cytokeratins (Nos. 8, 18, and 19) and neurofilament was observed. On ultrastructural examination, the tumor cells demonstrated paranuclear whorls of intermediate filament aggregates and occasional electron-dense granules. This unique cytokeratin- and neurofilament-staining pattern with coexpression enabled the Merkel cell carcinoma to be differentiated from other small cell malignant tumors that included metastatic neuroendocrine carcinomas from other regions. The follow-up 1 year after surgery and radiation showed that the patient remained disease free. Review of the literature revealed 11 cases of oral Merkel cell carcinomas with a predilection for the labial mucosa of older men. The mode of treatment and the clinical course of these cases are also presented, with an update on therapeutic management of Merkel cell carcinomas.

Radioiodinated somatostatin analog scintigraphy in small-cell lung cancer : Kwekkeboom DJ, Krenning EP, Bakker WH, Oei HY, Splinter TAW et al. University Hospital Dijkzigt, 40 Dr. Molewaterplein, 3015 GD Rotterdam. J Nucl Med 1991;32:1845–8

Somatostatin receptors have been characterized on biopsy specimens from small-cell lung carcinoma (SCLC) and on cultured human SCLC cells. We recently described the in vivo visualization of various somatostatin receptor-positive tumors, such as carcinoids and endocrine pancreatic tumors, after injection of 123I-Tyr-3-octreotide, a radiolabeled somatostatin analog. In the present study, this imaging procedure using 123I-Tyr-3-octreotide is reported in 11 patients with lung tumors. In five of eight patients with SCLC (63%), we were able to demonstrate tumor deposits using 123I-Tyr-3-octreotide scintigraphy. Unexpected metastases were found in two patients. In one of three patients with SCLC in whom tumor was not visualized, nonvisualization may have been caused by tumor necrosis and recent radiotherapy. In one of two patients with malignant small-cell tumors as described by Askin, the neoplasm was visualized. Like SCLC, these tumors are thought to derive from neuroendocrine cells. In one patient, a squamous-cell carcinoma and a bronchial adenoma were not visualized. We conclude that in the majority of patients with SCLC, the tumor and its metastases can be visualized using 123I-Tyr-3-octreotide scintigraphy. However, the value of this new technique in terms of specificity and sensitivity requires further studies in a larger group of patients.

A CASE REPORT OF ASKIN TUMOR IN A INFANT

A case of malignant small cell tumor of the thoraco-pulmonary region, so called Askin tumor, in a three year-old female complaining fever is described.In the chest plain roentrenogram and pulmonary CT scan, a spindle shaped chest wall mass situated on the right 5th rib was disclosed. The rib destructed. Ewing sarcoma or osteosarcoma was suspected. The chest wall resection with the 5th to 7th ribs, and the partial resection of the pulmonary segment 4 were performed. The tumor was elastic soft and 80×30×25 mm in size, a grayish-white appearance. The ribs, lung, and pleura were involved. Pathologically, the tumor was diagnosed as Askin tumor.Askin tumor is uncommon in infants and the prognosis is generally so dismal. Here the important of multidisplinary treatments as well as early diagnosis and operation is emphasized.

Metastatic tumors in the ovary: a problem-oriented approach and review of the recent literature.

Metastatic tumors account for a significant proportion of the ovarian tumors that cause major problems in diagnosis for the surgical pathologist. This subject is reviewed with a consideration of the various patterns and cell types encountered in these tumors. The first two categories considered, tumors with endometrioid-like and mucinous appearances, include a variety of neoplasms originating in the gastrointestinal tract and its appendages that simulate closely primary ovarian endometrioid and mucinous tumors. Other important categories reviewed include several varieties of metastatic tumors with follicle-like spaces, small cell malignant tumors, and tumors characterized by cells with abundant eosinophilic cytoplasm. The review also includes a discussion of the general considerations that are helpful in the distinction of primary and metastatic ovarian tumors. Important recent reports in the literature concerning metastatic tumors are additionally summarized.

Intra-abdominal Desmoplastic Small Round-Cell Tumor

Nineteen cases of a distinctive type of malignant small-cell tumor are presented. The main features of the entity are as follows: a predilection for adolescent males (mean age: 18.6 years); predominant or exclusive intra-abdominal location, with only inconstant and secondary organ involvement; nesting pattern of growth; focal rhabdoid features; intense desmoplastic reaction; immunohistochemical reactivity for epithelial [keratin, epithelial membrane antigen (EMA)], neural [neuron-specific enolase (NSE)], and muscle (desmin) markers; and highly aggressive behavior. It is proposed that this represents yet another member of the continuously enlarging and evolving family of small round (blue) cell tumors of infancy and childhood that features, more than any other member of this group, the capacity for simultaneous multidirectional phenotypical expression.

Diagnosis of a peripheral neuroectodermal tumour by fine needle aspiration

One case of malignant peripheral neuroectodermal tumour successfully diagnosed by cytology is presented. Although a Papanicolaou stained smear could not lead to a diagnosis more specific than a malignant small cell tumour, ancillary analytic methods performed on the cytologic material including immunocytochemistry and electron microscopy yielded the correct diagnosis of peripheral neuroectodermal tumour. This case demonstrates that a precise categorization of small round cell tumours may be achieved by cytology as long as some material is kept for immunocytochemical and ultrastructural studies.

Malignant small-cell tumor of the thoracopulmonary region: ‘Askin tumor’

Malignant small-cell tumor of the thoracopulmonary region (MSCT) is an uncommon neoplasm in children. We describe five cases diagnosed since 1981 that fulfill the criteria put forth by Askin et al. Surgery was performed for diagnosis or therapy in all patients. Two patients underwent open lung biopsy, only because of tumor extent. The other three had chest wall resections. All patients received radiotherapy and chemotherapy. Three patients presenting initially with extensive disease died at intervals of 2.5 to 7 months after diagnosis. Two patients are alive and disease-free at 16 and 24 months postdiagnosis. All five cases were reviewed for standard histology and differential immunohistochemistry. Electronmicroscopy and tissue cultures were done in 3 of the 5 patients. All five patients were neuron-specific enolase-positive. MSCT is an exclusion diagnosis not always readily made. Clinical course and pathologic expertise may point to the correct diagnosis.

Alveolar rhabdomyosarcoma metastatic to the ovary. A report of two cases and a discussion of the differential diagnosis of small cell malignant tumors of the ovary

Two young women with alveolar rhabdomyosarcoma metastatic to the ovary are reported. In each case, the ovarian involvement was detected within a few weeks of the discovery of a soft tissue mass by the patient. Symptoms attributable to the ovarian tumor dominated the initial clinical picture in one case. In the other case, the soft tissue mass was not appreciated by the treating physicians until after the diagnosis of rhabdomyosarcoma had been established by examination of the ovarian tumor. The ovarian tumor was unilateral in one case and bilateral in the other. One primary site was the right foot and the other primary site was the left forearm. These cases illustrate that metastatic alveolar rhabdomyosarcoma rarely enters into the differential diagnosis of a small cell malignant tumor of the ovary. Both patients experienced progression of their disease and died, despite aggressive chemotherapy, within 1 year of presentation.

Peripheral neurogenic tumors of the soft tissues in children and adolescents: a clinicopathologic study of 139 cases.

A review of over 900 soft tissue neoplasms in children and adolescents revealed 139 neurogenic tumors in 122 patients from newborn to 20 years of age, which had been accessioned in a 25-year period. Based upon clinicopathologic criteria, 84 (60%) tumors were regarded as unequivocally benign or borderline and the remaining 55 (40%) were malignant. The average age at diagnosis for the entire series was 10 years; the sex distribution was approximately equal; and the trunk (66, 48%) was the most frequent topographic site, followed by the head and neck (39, 29%) and extremities (31, 23%). Eighteen tumors (13%) were recognized at birth. Twenty-one patients (17%) had the stigmata of von Recklinghausen's neurofibromatosis (VRN). Neurofibromas and cellular peripheral nerve sheath tumors accounted for 43% (60 cases) of the diagnoses; these 60 neoplasms occurred in 41 patients, 12 of whom had VRN. The second largest category of neoplasms (38 cases, 28%) was the primitive neuroectodermal tumor (PNET) including the subset of "malignant small cell tumor of thoracopulmonary origin" or Askin tumor. The PNETs other than the Askin tumor (26 cases) presented mainly on the trunk (63%) and head and neck region (33%), showed a male predilection (58%) and had a mean age at diagnosis of 7 years. Askin tumors (12 cases) were, by definition, confined to the chest wall or thoracic cavity, showed a female predilection (71%), and presented in the second decade (82%, mean age 14 years). There were 16 (11%) malignant peripheral nerve sheath tumors, seven of which occurred in children with VRN. Six other categories of neurogenic tumors constituted the remaining cases. Our findings indicate that neurogenic neoplasms are an important nosologic group of soft tissue tumors in the pediatric population.

Extraskeletal Ewing's tumor with translocation t(11;22) in a patient with Down syndrome

A case of a small cell malignant tumor that occurred in the soft tissues of a 16-year-old boy with Down syndrome (47,XY,+21) is reported. The histologic and histochemical patterns were consistent with an extraskeletal Ewing's sarcoma (ES). The cytogenetic analysis of the tumor cells showed a t(11;22)(q24;q21), tetrasomy of chromosome 21, and trisomy of chromosome 14. The observation of a t(11;22) in an ES gives credit to the morphologic evidence in favor of the common (probably neuroectodermal) origin of the skeletal and extraskeletal forms of Ewing's sarcoma (ES). The possible pathogenetic significance of the constitutional trisomy of chromosome 21 in determining the occurrence of this tumor is discussed.

Periosteal Ewing's sarcoma.

Ewing's sarcoma is a small cell malignant tumor that usually arises in the medullary cavity of bone. Less frequently, it originates in soft tissue and may secondarily invade underlying bone. The origin of Ewing's sarcoma in a periosteal location without extension into either the bone or adjacent soft tissue has not been clearly documented. Other malignant tumors of bone (e.g., osteosarcoma) appear to have a somewhat better prognosis when confined between periosteum and bone. The case of a patient with a periosteal Ewing's sarcoma who received a radical excision and postoperative chemotherapy and who is without evidence of disease with over 2 years follow-up is reported.