Predominance Of Spindle Cells Research Articles

S1575 Isolated Gastrointestinal Gangliocytic Paraganglioma

Introduction: Gangliocytic paragangliomas of the GI tract are neuroendocrine tumors located in the second portion of the duodenum. Isolated gastrointestinal paragangliomas are rare, as paragangliomas are often associated with genetic conditions, including Von Recklinghausen disease (NF1) and Paraganglioma-Pheochromocytoma Syndrome (HPPS). We present the case of a 45 year-old woman --without the aforementioned hereditary conditions-- with symptomatic anemia found to have an ulcerated ampullary paraganglioma. Case Description/Methods: Our patient is a 45 year-old woman with a medical history of iron deficiency anemia and a remote cholecystectomy who presented with a four day history of melena, weakness, palpitations, and dyspnea. Her exam did not reveal epigastric tenderness, abdominal pain, rebound or guarding. Labs were notable for a microcytic anemia (Hgb: 3.4 g/dl) without transaminitis or elevated lipase. She was transfused 5 units packed red blood cells with appropriate response. A CT abdomen/pelvis was normal. Colonoscopy was without evidence of bleeding. Enteroscopy revealed a large mass in the second portion of the duodenum adjacent to the Ampulla of Vater. EUS characterized the mass as a well defined, hypoechoic submucosal lesion measuring 3 cm, without extension to the common bile duct and pancreatic duct. Fine needle biopsy revealed rare atypical spindle cells with high S-100 positivity. The patient underwent resection with a transduodenal ampullectomy. Surgical pathology demonstrated a 3.8 cm ampullary gangliocytic paraganglioma. Further genetic testing for HPPS was negative (FH, MAX, MEN1, NF1, RET, SDHA, SDHAF2, SDHB, SDHC, SDHD, TMEM127, VHL). She did not have evidence of upregulated hormonal activity, with normal levels of 24 hour urine metanephrines, TSH, and renin/aldosterone. Discussion: Gastrointestinal gangliocytic paragangliomas require a comprehensive work-up beyond fine needle biopsy to achieve a diagnosis. EUS/FNA is often inconclusive, as spindle cell predominance on cytology can mimic a schwannoma, necessitating further tissue sampling and/or resection. In addition, genetic testing and hormonal lab work is favored to rule out associated conditions such as NF1 and HPPS. Our patient’s diagnosis was made after transduodenal ampullectomy as the initial fine needle biopsy did not contain ganglion and epithelioid cells, additional neural crest derivatives. Post operatively, genetic and hyperadrenal testing were noncontributory, confirming the diagnosis of an isolated paraganglioma.Figure 1.: Large, submucosal mass in the second portion of the duodenum with 2 areas of surface ulceration. Lesion is close in proximity but not in direct continuity to the ampullary orifice.

Melanocytic Lesions- A Hospital-based Descriptive Study from Central Kerala, India

Introduction: Malignant melanoma is a tumour of melanocytic origin. There is considerable geographic variation in the incidence of melanocytic lesions and are related to exposure to sunlight and susceptibility of the population. Descriptive and statistical studies of melanocytic lesions are few among Indian populations. Aim: To describe and categorise melanocytic lesions, analyse their histological features and form evidence based data applicable to Indian population. Materials and Methods: The present descriptive study was conducted in Department of Pathology in a tertiary care centre in central Kerala, India from August 2013 to July 2016. Total duration of the study was 36 months starting from 2013 August to 2016 July. Melanocytic lesions received in Pathology Department for the study period were analysed. Data including age, gender, signs and symptoms, anatomical site, clinical and gross photographs were analysed. For each case, gross and histopathological examination were done. In some cases histopathological study alone was not diagnostic, so Immunohistochemistry (IHC) including Human Melanoma Black (HBM)-45 and Melan-A were conducted to establish melanocytic differentiation. Final statistical analysis was done by frequency measurements and cross tabulation using Statistical Package for the Social Sciences (SPSS) software version 17.0. Results: Total sample size was 57, among which 44 cases were from cutaneous sites (27 benign and 17 malignant) and 13 were from mucosal sites (2 benign and 11 malignant). Most of the cases were from above 60 years age group (35%). Anatomically, majority of cutaneous melanomas were from lower limb {15 (88.2%)} and majority of mucosal melanomas were from upper gastrointestinal tract {5 (38.4%)}. Although prominent nucleoli are said to be characteristic feature of melanomas, 8 out of the 28 total cases of melanomas had inconspicuous nucleoli (28.5%). When cell morphology of melanomas was studied, majority of cases had oval cells 10 (35.7%). It was also found that there was a significant correlation between spindle cell morphology and absence of pigment in melanomas (p-value=0.004). There was no association between mitosis in melanomas and vertical tumour diameter (p-value=0.1837). Conclusion: A female predominance was observed and the commonly effected age group was above 60 years. Intradermal nevi were the major benign melanocytic lesion, while the common site was lower limb among cutaneous melanomas and upper gastrointestinal tract among mucosal melanomas. A positive association between absence of pigment in malignant melanomas and predominance of spindle cells was found.

Immunohistochemical Study of Vasculogenic Mimicry and Angiogenesis in Melanocytic Tumors of the Eye and the Periocular Area.

The ability of a tumor to grow requires a sufficient blood supply. Microvascular density is considered the standard for assessing the neovasculature. Tumor cell vasculogenic mimicry refers to the formation of tumor cell-lined vessels that contribute to tumor neovascularization. The aim of the present work was to study angiogenesis and vasculogenic mimicry in benign and malignant melanocytic tumors of the eye and the periocular region. Histological sections from 118 patients were studied. Eighty-eight of the patients had nevi while the remaining 30 had malignant melanomas. Microvascular density was assessed by using antibodies against the endothelial cell markers CD31 and CD34. Vascular-like channels between neoplastic cells, that were not lined by endothelial cells and thus were negative for CD31 and CD34, represented areas of vasculogenic mimicry. Angiogenesis was more pronounced in melanomas compared to melanocytic nevi and was increased in melanomas with high mitotic index and/or epithelioid cell preponderance compared to melanomas with low mitotic index and/or spindle cell predominance. Vasculogenic mimicry was observed in many melanomas, while it was evident in the minority of benign nevi as well. The existence of vasculogenic mimicry in benign nevi might have prognostic implications.

Cytomorphological Study of Gastrointestinal Stromal Tumors: A Study of 40 Cases

Gastrointestinal stromal tumors (GIST) are a heterogenous group of neoplasms. So the aim is to assess the cases of spindle cell and epithelioid cell neoplasms of the GI tract and classify them as GIST and Non GIST morphologically. The study included 40 cases of GISTs. GIST cases were reviewed based on morphology and classified into “Risk of metastasis” categories. The small intestine was the most commonly involved site (46.67%), followed by stomach (30%). Based on the size of the tumor and mitotic activity, the tumors were categorized as high risk (62%), intermediate risk (17.67%), low risk (7.5%), and very low risk (5.04%). There was a spindle cell predominance (70.8%) among all the cases. Epithelioid cells were seen in 23.3% of the cases. Identifying mitotic figures and counting of GIST was associated with problems and were due to uneven distribution of the mitotic figures, variable thickness of the section and presence of inflammatory cells. In spite of the difficulty mitoses is still considered as a good prognostic marker.

A Case of Bleeding Rectal Ulcer Caused by Kaposiʼs Sarcoma in AIDS Patient

Introduction: AIDS-related Kaposi's sarcoma (KS) is a low-grade vascular tumor associated with human herpesvirus 8 (HHV-8) infection. We report the case of a 24 year old HIV male with rectal ulcer from disseminated KS with visceral involvement. Case: 24 year old male with AIDS/HIV (CD4 13) not on HAART, presented with rectal bleeding and weight loss. Examination revealed diffuse palpable lymphadenopathy and shiny papular, non-pruritic lesions in inguinal, scrotal and perirectal area. CT abdomen revealed lymphadenopathy and rectal inflammation. Initial infectious work up was negative for chlamydia, gonorrhea, HSV, CMV, stool for Cryptococcus, giardia, C.difficle, mycobacterium, pneumocystis smear. Colonoscopy showed large 3 cm necrotic, friable rectal ulcer and multiple focal erythematous lesions in rectum. Meanwhile, he developed epigastric pain with elevated liver tests, Ultrasound abdomen revealed new findings of splenomegaly, multiple nodules in liver concerning for abscesses vs. lymphoma. Based on findings, bone marrow and axillary lymph node biopsies were performed. Rectal ulcer and lymph node biopsies were positive for KS. The patient was diagnosed with disseminated KS involving the lung, GI tract, liver and spleen. He was started on HAART therapy. He was not a candidate for chemotherapy in view of multiorgan dysfunction. Patient eventually died. Discussion: AIDS related KS is the most common neoplasm in HIV patients, especially those with lower CD4 counts. Co-infection with HIV promotes the oncogenic capabilities of HHV-8, leading to the development of KS. KS is rare in the post HAART era. AIDS related KS preferentially affects homosexual or bisexual men. It frequently involves the skin, although extra cutaneous spread is common and may involve any organ. GI involvement is seen in 40% of untreated patients and portends a worse prognosis. Disease of the GI tract is typically asymptomatic but can present with abdominal pain, vomiting, diarrhea, weight loss, malabsorption and GI bleeding. Histopathology reveals a predominance of spindle cells. Immunohistochemical stains are positive for CD34 and CD31, which can confirm the diagnosis, although 10% of KS are CD34 negative. Treatment includes HAART therapy, chemotherapy is considered for more advanced disease using liposomal doxorubicin as the first line of treatment. KS should always be considered as a strong differential diagnosis in lesions of the gastrointestinal tract in HIV host.

Juvenile Granulosa Cell Tumors of the Testis

The clinical and pathologic features of 70 juvenile granulosa cell tumors (JGCTs) of the testis are presented. The patients were from 30 weeks gestational age to 10 years old; 60 of 67 (90%) whose ages are known to us were 6 months old or younger. Sixty-two underwent gonadectomy, 6 wedge excision, and 2 only biopsy. Twenty-six tumors were left sided and 22 right sided. Six occurred in an undescended testis and 2 in dysgenetic gonads. The most common presentation was a testicular mass (65%), followed by an "enlarging testis" (25%). Six of 14 patients in whom it was measured had "elevated" serum α-fetoprotein (AFP), likely physiologically, and 1 had gynecomastia. The tumors measured 0.5 to 5 cm (mean, 1.7 cm; median, 1.5 cm) and were most commonly well circumscribed and typically yellow-tan; approximately 2/3 had a cystic component, whereas 1/3 were entirely solid. Microscopic examination typically showed a lobular growth, punctuated in 67 cases by variably sized and shaped follicles containing material that was basophilic (21%), eosinophilic (44%), or of both characters (35%); 3 lacked follicles. In nonfollicular areas, the tumor cells typically grew diffusely but occasionally had a corded arrangement (26%) or reticular appearance (29%). The stroma was either fibrous or fibromyxoid; hemorrhage associated with hemosiderin-laden macrophages was focally seen in 16%. The tumor cells were mostly small to medium sized with round to oval nuclei containing inconspicuous nucleoli and moderate to abundant, but occasionally scant, pale to lightly eosinophilic, sometimes vacuolated, cytoplasm; nuclear grooves were infrequent (6%). Focal columnar morphology was seen in 27% of the tumors. Mitoses were plentiful in 37%, and apoptosis was prominent in 46%. Intratubular tumor was seen in 43% and entrapped seminiferous tubules in 70%. Lymphovascular invasion was present in 2 cases, rete testis involvement in 4, and necrosis in 1. Rare features/patterns included: regressed tumor with hyalinization and prominent blood vessels (13%), papillary growth (4%), basaloid morphology (1%), spindle cell predominance (1%), microcystic foci (1%), adult granulosa cell-like (1%) patterns, and hyaline globules (1%). Inhibin (16/18), calretinin (8/9), WT1 (6/7), FOXL2 (12/12), SF-1 (12/12), and SOX9 (6/11) were positive, whereas SALL4 and glypican-3 were consistently negative in the neoplastic granulosa cells. Only 1 of 10 tumors was focally positive for α-fetoprotein. JGCT is a rare neoplasm with a wide morphologic spectrum that also occurs rarely in undescended testes and dysgenetic gonads. The solid and reticular patterns may pose diagnostic challenges, but the lobular appearance and follicular differentiation are characteristic. Immunohistochemical stains may aid in its distinction from other tumors of young male individuals, particularly yolk sac tumor, a neoplasm that peaks at a somewhat later age. Twenty-four patients with follow-up, including 4 of 6 patients treated with wedge resection/biopsy, had no evidence of disease (2 to 348 mo; mean, 83 mo; median, 61 mo). One additional patient was alive at 260 months, but the disease status is unknown. The benign clinical course of all cases of JGCT with follow-up, despite often frequent mitotic activity, supports testis sparing surgery when technically feasible.

Mucin poor mucinous tubular and spindle cell carcinoma of the kidney, with nonclassic morphologic variant of spindle cell predominance and psammomatous calcification

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare type of kidney tumor that has only been recently described. The classic MTSCCs are polymorphic renal neoplasms characterized by small, elongated tubules lined by cuboidal cells and/or cords of spindled cells separated by pale mucinous stroma. Nonclassic morphologic variants and features of MTSC have not been well studied and rarely been reported. We report a challenging case of mucin-poor MTSCC with marked spindle cell predominance and focal psammomatous calcification in a 39-year-old man and describe its histologic and immunohistochemical features. Pathologists must be aware of the histologic spectrum of MTSCCs to ensure their accurate diagnosis.

Spindle cell lesions of the breast—the pathologic differential diagnosis

Spindle cell lesions of the breast represent an interesting diagnostic problem, as the differential diagnoses are wide. Diagnosing this is particularly problematic but important when encountered in a needle core biopsy, as treatments of different entities are different. In the histologic assessment of spindle cell lesions, the simplified approach is to evaluate the spindle cells and the accompanying epithelial cells. In the biphasic lesions with predominance of spindle cells with benign epithelial component, fibroepithelial lesions including fibroadenomas and phyllodes tumors are the most common, followed by pseudoangiomatous stromal hyperplasia, hamartoma and adenomyoepithelioma. For biphasic lesions with predominance of spindle cells with malignant epithelial component, the biphasic metaplastic carcinoma is likely. For monophasic lesions with pure pleomorphic spindle cell only, the monophasic metaplastic carcinoma is more common than the rare primary sarcomas like malignant fibrous histiocytoma, angiosarcoma, and other high grade sarcomas. In monophasic lesions with pure bland spindle cells only, the possible lesions include fibromatosis, fibromatosis like metaplastic carcinoma and other unusual conditions like dermatofibrosarcoma protuberance. By careful searching for the accompanying epithelial element, and with the aid of appropriate clinical input and judicious use of immunohistochemistry, many of these lesions can be confidently diagnosed in the needle core biopsy, thus facilitating appropriate treatments.

Expanding the Histologic Spectrum of Mucinous Tubular and Spindle Cell Carcinoma of the Kidney

Mucinous tubular and spindle cell carcinomas (MTSCs) are polymorphic neoplasms characterized by small, elongated tubules lined by cuboidal cells and/or cords of spindled cells separated by pale mucinous stroma. Nonclassic morphologic variants and features of MTSC have not been well studied. We identified 17 previously unreported MTSCs from Surgical Pathology and consultative files of the authors and their respective institutions and studied their morphologic features. A total of 10/17 cases were considered "classic," as described above, with 5/10 showing at least focal (20% to 50%) tubular predominance without apparent mucinous matrix. Alcian blue staining revealed abundant (>50%) mucin in all classic cases. Seven of 17 MTSCs were classified as "mucin-poor," with little to no extracellular mucin appreciable by hematoxylin and eosin. Four of these cases showed equal tubular and spindled morphology, 2 cases showed spindle cell predominance (70%; 95%), and 1 case showed tubular predominance (90%). In 5/7 mucin-poor cases, staining for Alcian blue revealed scant (<10%) mucin in cellular areas with the other 2 cases having 30% mucin. Unusual histologic features identified in the 17 cases were: foamy macrophages (n=8), papillations/well formed papillae (n=6/n=1), focal clear cells in tubules (n=3), necrosis (n=3), oncocytic tubules (n=2; 40%, 5%), numerous small vacuoles (n=2), heterotopic bone (n=1), psammomatous calcification (n=1), and nodular growth with lymphocytic cuffing (n=1). An exceptional case contained a well-circumscribed, HMB45-positive angiomyolipoma within the MTSC. MTSCs may be "mucin-poor" and show a marked predominance of either of its principal morphologic components, which coupled with the presence of other unusual features such as clear cells, papillations, foamy macrophages, and necrosis, may mimic other forms of renal cell carcinoma. Pathologists must be aware of the spectrum of histologic findings within MTSCs to ensure their accurate diagnosis.

Unclassified sex cord/gonadal stromal testis tumor with predominance of spindle cells

Unclassified sex cord/gonadal stromal tumors (SCSTs) of the testis comprised predominantly of spindle cells are extremely rare. It is important to differentiate these tumors from other testicular neoplasms, especially other types of sex cord/gonadal stromal tumors. In addition to histological criteria, immunohistochemistry plays an important role in the differential diagnosis. We describe a single case of this rare tumor type and discuss the differential diagnostics options based on a review of the related literature. The problem of the lack of reliable morphological prognostic factors is also addressed.

Primary pure intratesticular fibrosarcoma

Testicular sarcoma appears to be a rare stromal tumor usually of indolent course with potential for distant metastases. A pure primary intratesticular fibrosarcoma in a 71-year-old male is presented. By the time the tumor became evident metastases had already occurred widely. The course was rapidly fatal. A review of the literature yielded only one case reported previously. The present case illustrates that pure fibrosarcoma occurs occasionally as a stromal tumor and may be associated with a dismal prognosis. The diagnosis of pure fibrosarcoma should be made only after extensive sampling of the testicular tumor to rule out an associated germ cell component. The differential diagnosis also includes the fibroma of gonadal stroma origin and the unclassified sex cord-stromal tumor with a predominance of spindle cells.

Malignant melanoma in childhood

The clinical and histological features of 13 malignant melanomas in children under 13 years of age were compared with a control group of childhood nevi consisting of 15 Spitz nevi and 2 unusual compound nevocellular nevi. Six of the controls had been previously diagnosed as malignant melanoma. The clinical features proportionally mure common in malignant melanomas were bleeding, ulceration, itching, black color and variegated or mottled color. Recent enlargement and darkening in color were noted in both the malignant melanomas and Spitz nevi. Histological features which favoured malignancy were mitoses within 0.25mm of the dermal margins of the melanoma, mitoses >2mm/ 2 in the dermis, ulceration, surface exudate, large pigment granules and clear-cell differentiation. Features favouring Spitz nevi were absence of mitoses, predominance of spindle cells and diffuse maturation. Six of the 13 children with malignant melanomas died with their disease. I his study confirms that malignant melanoma does occur in childhood. Early recognition and management similar to adult melanoma is required.

Localized fibrous “mesothelioma” of pleura (submesothelial fibroma).A clinicopathologic study of 18 cases

Eighteen cases of solid fibrous tumors of the visceral pleura are studied. The series includes neoplasms of various sizes removed during the last 17 years at The Mount Sinai Hospital. Most tumors showed consistent gross and light microscopic features, such as encapsulation, preservation of pedicle, origin from visceral pleura, predominance of spindle cells with more or less hyalinized stroma, little or no pleomorphism or mitotic activity and no infiltration of the underlying lung. No sex predominance or relation to environmental pollutants was noted. Peak incidence was in the 6th decade of life. Total excision proved curative in all cases with no recurrences or complications. The cell of origin of this tumor appears to be a noncommitted mesenchymal cell present in the areolar tissue subjacent to the mesothelial lining.