Papillary thyroid carcinoma with fibromatosis-like stroma: a case report and review of the literature.

BACKGROUND: Papillary thyroid carcinoma (PTC) is a common neoplasia with multiple variants. One of these extremely rare and poorly described variants is PTC with fibromatosis-like stroma (PTC-FMS), a peculiar entity distinguished by its predominant mesenchymal component. This paper reviews the literature, discusses the diagnostic challenges, and the clinical and surgical implications of this type of tumor which has fewer than 30 cases reported in the literature. CASE PRESENTATION: We reported a case of PTC-FMS found in a 41-year-old Italian woman, who came to our Institute with a recent growth in the form of a mass on the neck. Further immunohistochemical examination showed ß-catenin aberrant staining both in the nuclei and cytoplasm of the mesenchymal cells. The patient underwent total thyroidectomy and received radioactive iodine (RAI) 2 months after surgery. CONCLUSION: Given the possibility of recurrence of PTC-FMS and the ineffectiveness of RAI therapy, complete surgical resection represents the main treatment for this type of tumor. Despite the fact that the specific nature of these lesions has yet to be determined, guidelines for classical PTC should be followed.

Pazopanib-related secondary polycythemia in metastatic myxofibrosarcoma: A case report and review of the literature.

INTRODUCTION: Pazopanib, a tyrosine kinase inhibitor (TKI), is a standard treatment for various tumours, including metastatic non-adipocytic soft-tissue sarcomas. In literature, erythrocytosis has been described as a TKI-related condition. CASE REPORT: A 59-year-old man underwent surgical removal of a sub-scapular mass consistent with myxofibrosarcoma. After distant relapse, he first started chemotherapy, and then Pazopanib. He was found to have increased levels of hemoglobin (Hb) and hematocrit (Hct). He was asymphtomatic, with no history of pulmonary disease nor smoking habit. Erythropoietin (EPO) level was higher than normal. A polycythemia vera was ruled out.Management & outcome: The patient started a prophylactic therapy with lysine acetylsalicylate, and we observed a reduction of Hb, but not Hct. Due to disease progression, we interrupted Pazopanib. After a week from drug discontinuation, Hb levels got back to the normal range, Hct was lowering. We decided not to perform phlebotomy, considering the declining trend in Hb and Hct values and the absence of symptoms. DISCUSSION: We postulated a Pazopanib-related secondary erythrocytosis, since Hb and Hct levels increased from baseline during treatment, then normalized when Pazopanib was discontinued. We used the Naranjo Nomogram to assess the correlation between the adverse effect and Pazopanib, the correlation was "Probable", a score of 5. To the best of our knowledge, this is the first case report of Pazopanib-related secondary polycythemia in a patient with sarcoma. It is important to pay attention to blood count and to any symptoms potentially related to erythrocytosis in patients treated with TKIs.

Experimental models of pancreatic cancer desmoplasia.

Desmoplasia is a fibro-inflammatory process and a well-established feature of pancreatic cancer. A key contributor to pancreatic cancer desmoplasia is the pancreatic stellate cell. Various in vitro and in vivo methods have emerged for the isolation, characterization, and use of pancreatic stellate cells in models of cancer-associated fibrosis. In addition to cell culture models, genetically engineered animal models have been established that spontaneously develop pancreatic cancer with desmoplasia. These animal models are currently being used for the study of pancreatic cancer pathogenesis and for evaluating therapeutics against pancreatic cancer. Here, we review various in vitro and in vivo models that are being used or have the potential to be used to study desmoplasia in pancreatic cancer.

Familial multiple discoid fibromas: unique histological features and therapeutic response to topical rapamycin.

Familial multiple discoid fibromas is a rare genodermatosis that bears some resemblance to Birt-Hogg-Dubé syndrome but is not associated with mutations in the folliculin (FLCN) gene or systemic manifestations. It is characterized by the development of papules over the face and pinnae early in life. Histological findings are of fibrovascular tumours adjacent to hair follicles without features characteristic of fibrofolliculomas, which have recently been termed discoid fibromas. We present siblings with multiple papules over the face and pinnae that developed in childhood. Histological specimens from both siblings demonstrated discoid fibromas, but with some lesions exhibiting an unusual keloidal-like pattern with thick hyalinized collagen fibres surrounded by plump spindle and histiocyte-like cells. FLCN gene mutations were not found. We report on clinical improvement with topical rapamycin solution (1 mg mL(-1)) applied daily to the face for 4 months. Therapeutic response to topical rapamycin may provide a clue to the underlying genetic basis of this condition.

Unilateral pachydermodactyly misdiagnosed as juvenile idiopathic arthritis: A case report.

RATIONALE: Pachydermodactyly is a rare, benign disease that can manifest in healthy adolescent boys as painless, spindle-shaped, soft-tissue swelling of the proximal interphalangeal joints in the hand. It is usually bilateral, with symmetrical joint enlargement. There are relatively few documented cases of pachydermodactyly worldwide, signifying either a low incidence or lack of recognition by physicians; therefore, its diagnosis is challenging. PATIENT CONCERNS: A 16-year-old boy with a 3-year history of painless unilateral swelling of the proximal interphalangeal joints of his left hand was misdiagnosed with juvenile idiopathic arthritis and was treated with oral methotrexate for 1 year. He had a history of frequent finger cracking. DIAGNOSIS: He had normal levels of inflammatory markers, including erythrocyte sedimentation rate and C-reactive protein. His autoantibody profile results were normal, and radiography of his hands showed soft tissue swelling with no bone abnormalities. Therefore, the patient was diagnosed with Parkinson disease. INTERVENTIONS: Methotrexate was discontinued, and a skin biopsy was performed, which revealed hyperkeratosis in the epidermis with thick collagenous fibers in the dermis. Therefore, the patient was informed of the benign nature of the disease and was advised to stop cracking his fingers. OUTCOMES: After regular follow-up, there was no progression of the patient's symptoms, and repeated blood tests revealed normal results. LESSONS: Pachydermodactyly should be considered in the differential diagnosis of painless swelling in adolescent men with normal blood testing. Early recognition of this rare benign condition helps physicians appropriately reassure the patient and his parents without exposing them to unnecessary therapy.

Imatinib for progressive and recurrent aggressive fibromatosis (desmoid tumors): an FNCLCC/French Sarcoma Group phase II trial with a long-term follow-up.

BACKGROUND: Imatinib evaluated as a new treatment option in patients with recurrent or established progressive aggressive fibromatosis/desmoid tumor (AF/DT). PATIENTS AND METHODS: Forty patients with unresectable and progressive symptomatic AF/DT were treated with imatinib (400 mg/day for 1 year) in a Simon's optimal two-stage phase II study (P(0) = 10%, P(1) = 30%, α = 5%, ß = 10%). The primary end point was non-progressive at 3 months (RECIST). RESULTS: The study population consisted of 28 women and 12 men, with a mean age of 41 (range 20-72 years). Most of the primary sites were extra-abdominal (24, 54.5%). Familial adenomatous polyposis was observed in six (15%) cases. The median follow-up was 34 months. Imatinib toxicity was similar to that previously reported in literature. Tumor assessment was validated by a central independent radiology committee for 35 patients At 3 months, one (3%) complete and three (9%) partial confirmed responses were observed. The non-progression rates at 3, 6 and 12 months were, respectively, 91%, 80% and 67%. The 2-year progression-free and overall survival rates were 55% and 95%, respectively. Two patients with mesenteric AF/DT died from progressive disease. CONCLUSION: Imatinib is active in the treatment of recurrent and progressive AF/DT, providing objective response and long-term stable disease in a large proportion of patients.

Sirolimus therapy for fibromatosis and multifocal renal cell carcinoma in a child with tuberous sclerosis complex.

A male with tuberous sclerosis complex (TSC) developed a chest wall fibromatosis and bilateral multifocal renal cell carcinoma (RCC). The fibromatosis tumor was initially resected during infancy but recurred 5 years later. At that time, bilateral RCC was also detected, leading to the resection of the more extensively affected right kidney. In an attempt to avoid bilateral nephrectomies, the patient was treated with the mTOR inhibitor sirolimus. Within 6 months of therapy, the fibromatosis and remaining RCC tumors responded substantially with minimal adverse effects.

Fibroblastic rheumatism: fibromatosis rather than non-Langerhans cell histiocytosis.

BACKGROUND: Fibroblastic rheumatism is a unique fibro-proliferative disease affecting the skin and joints. It is characterized by distinctive clinical and histological features related to benign spindle-shaped cells proliferation. Pediatric reports are scarce in the literature. OBJECTIVE: We describe here a new case in a 10-year-old boy and discuss the potential origin of the cell proliferation. METHODS: Clinical findings, radiology, microscopic examination and outcome are reviewed. Histopathology and immunochemistry studies were performed on skin biospies using CD68, CD163, desmin, factor XIIIa, CD34, smooth muscle actin, PS100, epithelial membrane antigen, and calponin. RESULTS: Histological sections disclosed a rather circumscribed nonencapsulated nodular infiltrate, invading the dermis and the upper subcutaneous tissue, consisted of a proliferation of spindle or stellate-shaped cells and thickened collagen fibers. Orcein staining showed disappearance of the elastic network. Aponeurosis and muscle were normal. A mild perivascular lymphohistiocytic infiltrate was noted. Calponin-staining was less strongly expressed as SMA, and some of them but not all were CD68 positive, as well. On the other hand, all were CD34, CD163, FXIIIa, PS100, EMA and desmin-negative. CONCLUSION: The true origin of these cells remains unclear. Some authors have speculated a histiocytic origin. However, immuno-chemical staining in our case failed to confirm this hypothesis and instead supported a fibroblastic/myofibroblastic origin. Given the clinical course and the histological and immunohistochemical results, we suggest that FR should be added to the group of fibromatoses.

PET surveillance of patients with Ewing sarcomas of the trunk: Must the lower legs be included?

AIM: FDG-PET(/CT) is frequently used in surveillance of Ewing sarcoma (ES) patients. Since ES and PNET (primitive neuroectodermal tumours) may cause peripheral metastases some centers routinely recommend whole body PET acquisition from head to toe what may necessitate repositioning of the patient and thus extending examination time. It is not clear yet whether inclusion of lower leg adds to the diagnostic accuracy of PET scanning, especially in primary tumors of the trunk. PATIENTS, METHOD: 40 patients with ES and PNET of the trunk who were referred for surveillance after primary therapy with complete remission, were evaluated retrospectively: 27 men, 13 women; mean age at diagnosis 16.3 (3-35) years. At the time of diagnosis 28 patients had localized and 12 metastatic disease. Almost all of the patients had undergone a combined chemotherapy with surgery or/and radiotherapy. 156 follow-up PET scans of the legs of these patients were evaluated retrospectively. RESULTS: only in three (1.9%) of 156 scans a pathologic FDG accumulation was attributed to metastatic disease of the lower extremities. In these cases the observation of metastatic disease in the legs did not alter therapy, since in all three cases a multifocal disease progression was observed. CONCLUSION: scanning of the lower legs may be omitted during follow-up in patients in whom the primary tumor was located in the trunk and in whom no clinical signs pointing to metastases in the lower legs are present. This provides a sufficient diagnostic power and a shorter examination time, thus increasing patient comfort and scanner availability.

Pachydermodactyly in a young girl: cutaneous manifestation of a psychiatric disorder?

; Pachydermodactyly is a benign process characterized by painless fusiform skin swellings affecting radial and ulnar aspects of the proximal interphalangeal joints of the fingers. We report a case of this condition in a young girl, suggesting a major role of psychiatric disorder in the development of cutaneous lesions.

Low-grade Fibromyxoid Sarcoma: Treatment Outcomes and Efficacy of Chemotherapy.

BACKGROUND: Low-grade fibromyxoid sarcoma (LGFMS) is a rare sarcoma subtype with a generally indolent pattern of clinical behaviour, but treatments for advanced disease are limited. PATIENTS AND METHODS: A retrospective search of a prospectively maintained institutional database identified 102 patients treated from December 1994 to August 2018. We evaluated the outcome of patients and the efficacy and safety of non-surgical therapies in LGFMS. RESULTS: Ninety-four out of 102 (92.2%) underwent primary resection, seven (6.9%) were treated with systemic therapy and one (1.0%) is currently being treated with pre-operative radiotherapy. The RECIST 1.1 response rate to first-line chemotherapy was 0%, and median progression-free survival was 1.84 months (95% confidence intervaI=0.10-3.6 months). CONCLUSION: Conventional systemic therapy has limited efficacy in advanced LGFMS.

A case of Meigs syndrome mimicking metastatic breast carcinoma.

BACKGROUND: Adnexal masses are not uncommon in patients with breast cancer. Breast cancer and ovarian malignancies are known to be associated. In patients with breast cancer and co-existing pleural effusions, ascites and adnexal masses, the probability of disseminated disease is high. Nevertheless, benign ovarian masses can mimic this clinical picture when they are associated with Meigs' syndrome making the work-up and management of these patients challenging. To our knowledge, there are no similar reports in the literature and therefore we present this case to highlight this entity. CASE PRESENTATION: A 56-year old woman presented with a 4 cm, grade 2, invasive ductal carcinoma of her left breast. Pre-treatment staging investigations showed a 13.5 cm mass in her left ovary, a small amount of ascites and a large right pleural effusion. Serum tumour markers showed a raised CA125 supporting the malignant nature of the ovarian mass. The cytology from the pleural effusion was indeterminate but thoracoscopic biopsy failed to show malignancy. The patient was strongly against mastectomy and she was commenced on neo-adjuvant Letrozole 2.5 mg daily with a view to perform breast conserving surgery. After a good response to the hormone manipulation, the patient had breast conserving surgery, axillary sampling and laparoscopic excision of the ovarian mass which was eventually found to be a benign ovarian fibroma. CONCLUSION: Despite the high probability of disseminated malignancy when an ovarian mass associated with ascites if found in a patient with a breast cancer and pleural effusion, clinicians should be aware about rare benign syndromes, like Meigs', which may mimic a similar picture and mislead the diagnosis and management plan.

Fibromatosis of the neck causing airway obstruction managed effectively with weekly low-dose methotrexate and vinblastine.

Fibromatosis is a rare disease with benign histology. Its infiltrative growth pattern may prevent complete resection. We report a case of a 40-year-old woman with fibromatosis of the neck requiring an emergency operation for acute upper airway obstruction. Gross residual tumour was left behind but excellent tumour shrinkage was achieved by using weekly low-dose methotrexate and vinblastine. Despite the use of newer agents such as imatinib, cytotoxic chemotherapy remains an efficacious treatment for inoperable fibromatosis.

Hormone-dependent gynaecological disorders: a pathophysiological perspective for appropriate treatment.

Hormonal changes are involved in several gynaecological disorders. Correct functioning of the hypothalamus-pituitary-ovarian (HPO) axis is critical for ovulatory function, as well as the growth and differentiation of uterine tissue (myometrium and endometrium). However, the correct functioning of other endocrine glands (thyroid, adrenal cortex, pancreas) is also crucial for correct reproductive function. Genes and environmental factors have an influence on women's fertility through their effect on hormonal function. Consequently, dysfunction of the HPO axis and/or other endocrine systems may cause infertility and gynaecological disorders. The pathogenetic basis can be used to help make the correct clinical decision for treating these diseases. Disturbances related to the menstrual cycle, i.e. amenorrhoea, polycystic ovary syndrome (PCOS) and premenstrual syndrome (PMS), have a close correlation with hypo- or hypersecretion of hormones of the HPO axis. The roles of hypothalamic neurohormones and neurotransmitters in the various forms of amenorrhoea and PMS are well established. PCOS has a complex endocrine/metabolic origin, so a variety of hormonal treatments have been proposed. Hormone derangement has also been proposed as the cause of endometriosis and uterine fibroids. These disorders do not have hyper- or hyposecretion of reproductive hormones, but hyperactivity of oestrogen receptors coupled with a genetic predisposition. The relevance of the endocrine changes is confirmed by the clinical effectiveness of hormonal treatments. In order to establish the correct treatment approach in gynaecological disorders, it is important to understand the endocrine pathophysiology.

Low-dose chemotherapy for extra-abdominal desmoid tumor.

OBJECTIVE: To assess the outcome of patients with extra-abdominal desmoid tumor treated with low dose chemotherapy (methotrexate and vinblastine) both for tumor response and treatment related toxicity. METHODS: We retrospectively reviewed the outcome of 12 patients who underwent low dose chemotherapy for extra abdominal desmoid of different locations. The study took place in the McGill University Health Center, Montreal, Canada between 1996 and 2003. We evaluated the patients for their compliance, tumor response, complications of treatment, and impact of treatment on symptoms. There were 7 females and 5 males with a mean age of 46 years. RESULTS: Disease related morbidity included pain in 7 patients, functional limitation in 7 and cosmetic defects in 3. The mean tumor size was 11 cm (3-20 cm). The mean follow-up was 43 months (15-71 months). Chemotherapy was administered weekly. Complications were significant. Only 2 patients did not experience the toxicity. According to Response Evaluation Criteria in Solid Tumors, 6 tumors showed a partial response and 6 remained stable. None showed progression. Of the 7 patients who had painful tumors, 6 achieved significant symptom relief. Function was improved in 3 and restored to normal in 4. Cosmesis was improved in 2 of the 3. At latest follow-up, tumors remained stable in 8, one has markedly regressed and 3 exhibited progression at an average of 54 months. Only one patient required surgery. The only long term side effect was a sensory peripheral neuropathy. CONCLUSION: Low dose chemotherapy was found to be a valuable adjunct to prevent local progression and improve symptoms.

Effects of aglepristone, a progesterone receptor antagonist, in a dog with a vaginal fibroma.

A 12-year-old, entire, nulliparous crossbreed female dog was presented with a history of vulval bleeding, bulging of the perineum and faecal tenesmus. A firm, non-painful perineal mass, measuring 9.11x5.4 cm, with erythema was detected. Abdominal radiography showed compression and elevation of the rectal ampulla. A dose of 10 mg/kg aglepristone was administered subcutaneously on days 1, 2, 8, 15, 28 and 35. An incision biopsy was taken on day 15 and immunohistochemical analysis showed that the majority of neoplastic cells expressed progesterone receptors. Both the cutaneous erythema and the faecal tenesmus had resolved by day 28. A 50 per cent reduction in size was observed by day 60 (surgical excision). This study shows that benign tumours of the vagina of the dog that contain progesterone receptors can be reduced in size in a palliative or neoadjuvant setting using the progesterone receptor antagonist aglepristone.

Treatment of submandibular fibromatosis with chemotherapy and surgery. A case report.

Fibromatoses are a broad group of fibrous tissue proliferation that arise from the musculoaponeurotic structures. Because of the locally aggressive behaviour and the high recurrence rate of these tumors, various treatment options are suggested but there is still no optimal therapy for these diseases. This paper describes a case of infantile fibromatosis of the submandibular region, which was successfully treated with an interdisciplinary approach using chemotherapy and surgery. A three-year-old girl with a growing submandibular mass over a period of six months is described. The tumor was clinically aggressive, causing bone erosion and invading adjacent soft tissue structures. The diagnosis of infantile fibromatosis was established on histological and immunohistochemical findings. With a combined treatment based on ''low-dose'' chemotherapy including vinblastine and methotrexate and surgery; complete remission was achieved in 30 months. Management of head and neck fibromatoses in child-hood needs a specific approach. Combined treatment by chemotherapy and nonmutilating surgery seems to offer the best potential for cure.

Recurrent Severe Hypoinsulinemic Hypoglycemia Responsive to Temozolomide and Bevacizumab in a Patient With Doege-Potter Syndrome.

Nonislet cell tumor hypoglycemia is rare. We highlight the diagnosis and treatment of recurrent severe hypoglycemia in a 49-year-old woman with malignant solitary fibrous tumor of the pleura (Doege-Potter syndrome). The clinical, laboratory and radiologic findings of the case are presented and a brief literature review is provided. Of note, imaging studies showed a large mass in the right hemithorax and pathology and immunehistochemical stains confirmed a malignant solitary fibrous tumor of the pleura. She was a poor surgical candidate owing to a large tumor burden. She was treated with a combination of temozolomide and bevacizumab to which she responded with resolution of hypoglycemia. The treatment of choice for hypoglycemia in patients with the Doege-Potter syndrome is surgical excision. We here report that a combination of temozolomide and bevacizumab may be a viable option in patients with inoperable disease.