The diagnostic utility of zinc E-box 1 (ZEB1) transcription factor for identification of pulmonary sarcomatoid carcinoma in cytologic and surgical specimens.

OBJECTIVE: Although uncommon, pulmonary sarcomatoid carcinoma carries a worse prognosis due to poor chemotherapeutic response. Currently, a histologic spindle and/or giant cell component indicates sarcomatoid differentiation, with zinc E-box binding homeobox 1 (ZEB1) implicated in promoting epithelial-mesenchymal transition. However, diagnostic use of ZEB1 in limited specimens, including cell block (CB) preparations, remains unclear. MATERIALS AND METHODS: Pulmonary sarcomatoid (SARC, n = 15), typical (TC, n = 10) and atypical carcinoid (AC, n = 10), small cell (SCLC, n = 8) and large cell neuroendocrine carcinoma (LCNEC, n = 9), squamous cell carcinoma (SQ, n = 7), and adenocarcinoma (ADC, n = 7) CBs along with 69 SARCs, 20 TCs, 21 ACs, 9 SCLCs, 10 LCNECs, 71 SQs, 402 ADCs, 16 large cell carcinoma (LCC) and 17 other thoracic tumor (OT) surgical specimens between 2007 and 2018 were retrieved. ZEB1 (Sigma Aldrich, St. Louis, Mo and Novus Biological, Centennial, Colo) immunohistochemistry was graded 1+ to 3+, with ≥1+ and >5% staining considered positive. RESULTS: Nuclear ZEB1 was seen in 80% SARC (12/15), 0% TC (0/10), 0% AC (0/10), 12.5% SCLC (1/8) and 11.1% LCNEC (1/9), 0% SQ (0/7), and 0% ADC (0/7) CBs. In surgical specimens, 75.4% SARCs (52/69), 0% TCs (0/20), 0% ACs (0/21), 11.1% SCLCs (1/9), 30% LCNECs (3/10), 0% SQs (0/71), 0.2% ADCs (1/402), 12.5% LCCs (2/16), and 11.8% OTs (2/17) demonstrated ZEB1. ZEB1 sensitivity and specificity in cytology and surgical specimens were 80% and 96.1%, and 75.4% and 98.1%, respectively. CONCLUSIONS: ZEB1 is sensitive and highly specific for pulmonary sarcomatoid carcinoma in limited cytologic and surgical specimens. Diagnostic pitfalls include high-grade neuroendocrine tumors and large cell carcinoma, which are resolvable by morphologic considerations.

Osteoclast-like giant cell-rich carcinomas of the lung: a clinicopathological, immunohistochemical, and molecular study of 3 cases.

Three cases of primary carcinomas of the lung each with an extensive osteoclast-like giant cell component are presented. The patients are 3 men between the ages of 58 and 67 years (average, 62.5 years) who presented with nonspecific symptoms. A history of malignancy, infectious, or granulomatous disease was negative in all the patients. Diagnostic imaging disclosed the presence of a large intrapulmonary mass; in 1 case in the right upper lobe and in 2 cases in the right lower lobe. Surgical resection via lobectomy was performed in the 3 patients. Grossly, the tumors were described as soft, friable intrapulmonary masses, reddish in color, and measuring from 6 to 13 cm in largest diameter. Histologically, the tumors were each characterized by the extensive presence of a multinucleated osteoclast-like giant cell component, which represented approximately 80% of the tumor mass. The osteoclast-like giant cell component was admixed with a sarcomatoid carcinoma in 2 cases and an adenocarcinoma in 1 case. Immunohistochemistry showed that the osteoclast-like giant cells were positive for CD-68, cathepsin K, and histone H3, whereas the carcinoma component was positive for keratin, thyroid transcription factor-1, and histone H3 (patchy). Molecular studies were performed in 2 patients with negative results. Clinical follow-up was obtained in 2 patients; 1 died 14 months after initial diagnosis, whereas 1 remains alive 6 months after initial diagnosis. One patient was lost to follow-up. The current neoplasms represent an unusual type of lung carcinoma that needs highlighting as a separate type from conventional giant cell carcinoma.

Prostatic Adenocarcinoma With Focal Pleomorphic Giant Cell Features: A Series of 30 Cases.

Prostatic adenocarcinoma with focal pleomorphic giant cell features is rare with the only prior series consisting of 6 cases. From 2005 to 2018, we identified 29 cases from our consult service and 1 case from our own institution. Men ranged in age from 39 to 90 years (median=75.5). Diagnostic specimens consisted of needle biopsies (n=13); transurethral resections (n=7), urethral/bladder biopsies (n=8), radical prostatectomy (n=1), and orchiectomy (n=1). In all cases, there was usual acinar prostatic adenocarcinoma, where the highest grade in all cases was Gleason score 9 to 10 (Grade Group 5). On average, 68% of the involved cores had cancer with a maximum percent of cancer averaging 55%; on average, transurethral resections had 85% of the area involved by cancer. Areas of cancer showing pleomorphic giant cell features were focal (<5%). Two of the needle biopsies showed extraprostatic extension. The radical prostatectomy had seminal vesicle invasion and positive margins with lymphovascular invasion. Prostatic adenocarcinoma with focal pleomorphic giant cell features is always accompanied by extensive usual acinar prostate adenocarcinoma where the highest grade in all cases was Gleason score 9 to 10 (Grade Group 5). Although the pleomorphic component is focal, it can mimic urothelial carcinoma. IHC can be misleading as PSA staining is often negative or focal in both the pleomorphic and usual prostatic adenocarcinoma components. NKX3.1 is the most sensitive prostate marker, but was still focal in 1 usual prostatic adenocarcinoma and negative in 2 pleomorphic components. Prostatic adenocarcinoma with focal pleomorphic giant cell features has a dismal prognosis. In men with no prior diagnosis of prostate adenocarcinoma and >1-year follow-up, 7/19 (37%) were dead at a median of 8 months after diagnosis. Of the 7 men with a prior history of prostate adenocarcinoma, 4/7 (57%) were dead at a median of 7 months after diagnosis of recurrent prostate adenocarcinoma with pleomorphic giant cell features.

Giant cell tumour of the patella with local recurrence: successful management with excision, curettage and artificial bone grafting.

Primary patellar neoplasms are rare, comprising 0.12% of primary bone tumours; thus, no standardised treatment related to staging exists. 70%-90% of primary patellar neoplasms are benign or intermediate with giant cell tumour (GCT) being the most common. GCTs are locally aggressive, have a high recurrence rate and metastasise in 1%-2%. We report the case of a 23-year-old man with histologically confirmed recurrent GCT of the patella to demonstrate that aggressive surgical management options described in the literature, such as patellectomy with or without complex reconstruction, may be excessive and cause patients undue morbidity. Initially, the patient underwent intralesional curettage with excellent recovery, but presented again with a local recurrence within a year. A further definitive operation was performed which included excision of the inferior pole followed by curettage of the patellar body and artificial bone grafting. The patient made a good recovery and at 5-year follow-up has maintained good function.

Spondylectomy for Giant Cell Tumor After Denosumab Therapy.

STUDY DESIGN: A case report. OBJECTIVE: To report a case of the lumbar giant cell tumor (GCT) utilizing a new clinical treatment modality (denosumab therapy), which showed a massive tumor reduction combined with the L4 spondylectomy. SUMMARY OF BACKGROUND DATA: There are some controversies about spinal GCT treatments. Denosumab has provided good clinical results in terms of tumor shrinkage, and local control in a short-time follow-up clinical study phase 2, although for spinal lesions, it has not been described. Nonetheless, "en bloc" spondylectomy has been accepted as being the best treatments modalities in terms of oncological control. METHODS: A case study with follow-up examination and series radiological assessments 6 months after therapy started, followed by a complex spine surgery. RESULTS: The denosumab therapy showed on the lumbar computed tomography scans follow-up 6 months later, a marked tumor regression around 90% associated to vertebral body calcification, facilitating a successful L4 spondylectomy with an anterior and posterior reconstruction. The patient recovered without neurological deficits. CONCLUSION: A new therapeutic modality for spinal GCT is available and showing striking clinical results; however, it is necessary for well-designed studies to answer the real role of denosumab therapy avoiding or facilitating complex spine surgeries as spondylectomies for spinal GCT. LEVEL OF EVIDENCE: 5.

Primary giant cell carcinomas of the lung: a clinicopathological and immunohistochemical analysis of seven cases.

AIMS: Seven cases of primary giant cell carcinomas of the lung are presented. METHODS AND RESULTS: The patients were five women and two men between the ages of 48 and 72 years (average: 63 years). Clinically, the patients presented with symptoms of cough, chest pain, dyspnoea and general malaise. Diagnostic imaging revealed the presence of intrapulmonary masses; five tumours were located in the right lung and two in the left, with a general predilection for the upper lobes. All patients underwent surgical resection and staging of their tumours. Five patients were staged as T2 and T3 with nodal metastasis, while two patients in stages T1 and T3, respectively, had no nodal disease. Histologically, the giant cells were typed as syncytiotrophoblast-like or 'null type', according to the expression of ß-human chorionic gonadotrophin or expression of cytokeratin alone. Follow-up information revealed that five patients died within a period of 1-3 years, while two patients remain alive between 1 and 3 years. CONCLUSIONS: The cases presented herein highlight the importance of separating these tumours from the group of sarcomatoid carcinomas and analysing them carefully by immumohistochemical means, as we believe that these neoplasms represent a specific tumour entity.

Locally advanced undifferentiated carcinoma with osteoclast-like giant cells of the pancreas.

Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas (UCOGCP) is an unusual pancreatic neoplasm that represents < 1% of all pancreatic malignancies. Moreover, the giant cells of UCOGCP morphologically resemble the benign giant cells of bone tumors. Due to the rarity of this tumor type, the histogenesis and biologic behavior of UCOGCP remain controversial. Here, we report a case of UCOGCP that exhibited an invasive growth pattern involving infiltration of the adjacent bowel loop and portal vein, as well as superior mesenteric vein thrombosis. The patient underwent a distal pancreatectomy with splenectomy and partial colectomy, followed by four cycles of gemcitabine chemotherapy. No evidence of recurrence was detected after ten years. In addition to this case, clinical information on other UCOGCP cases reported in the English literature is summarized.

Gigantomastia gestacional: como abordar essa situação clínica / Gestational gigantomastia: how to address this clinical situation

A gigantomastia gestacional é uma desordem rara, na qual ocorre o crescimento excessivo e rápido das mamas, culminando com edema e congestão venosa das mesmas, além de ocasionar dor, ulceração da pele e infecção local. Estas complicações, em alguns casos, levam à necessidade de mastectomia de emergência ou abortamento induzido. A hipótese etiológica mais aceita é a de que exista uma estimulação anormal do tecido mamário, que pode ser desencadeada por níveis excessivos de hormônios ou por uma hipersensibilidade deste tecido a níveis hormonais normais. Apesar de a mama regredir após a gestação, raramente volta ao estado original; portanto, a redução da mama através de mastectomia ou mamoplastia geralmente é necessária. Além disso, é grande o risco de recorrências em gestações futuras. Os autores relatam o caso de gigantomastia em uma primigesta, com necessidade de interrupção da gravidez, devido ao risco de morte materna, e posterior intervenção cirúrgica com mamoplastia redutora.

Gestational gigantomastia is a rare disorder characterized by an excessive and rapid enlargement of the breasts, resulting in edema and venous congestion of breast tissue. It is a painful condition that causes skin ulceration and local infection. In some cases, these complications lead to an emergency mastectomy or induced abortion. The most probable etiology is an abnormal stimulation of breast tissue that is probably triggered by an abnormally elevated level of hormones or by the hypersensitivity of breast tissue to normal hormone levels. Although the breast volume decreases after pregnancy, it rarely returns to its original state; therefore, breast reduction through mastectomy or mammaplasty is usually necessary. Moreover, there is a high likelihood of recurrence in subsequent pregnancies. The authors report a case of gigantomastia in a primigravida that required pregnancy termination, because of the risk of maternal death, and a subsequent breast reduction surgery.

Metástase gigante de carcinoma papilífero / Giant metastasis of thyroid papillar carcinoma

O carcinoma papilífero da tireoide, o mais comum deste órgão, geralmente se apresenta como lesões parenquimatosas pequenas e, eventualmente, com metástases cervicais numerosas, raramente volumosas. É descrito um caso raro de uma paciente do gênero feminino, 44 anos, com um tumor cervical anterior, nodular e volumoso há nove anos. Após o tratamento cirúrgico, o anatomopatológico mostrou tratar-se de metástases linfonodais de carcinoma papilífero. O objetivo deste estudo é relatar um caso clínico de apresentação incomum de carcinoma papilífero da tireoide, de diagnóstico inicial difícil e apresentando-se com metástases linfonodais volumosas. Arq Bras Endocrinol Metab. 2014;58(9):967-9 Papillary thyroid carcinoma, the most common type of thyroid cancer is usually presented as small parenchymatous lesions and, eventually, with cervical lymph node metastasis, rarely voluminous. Here we describe a rare case of a 44-year-old woman presenting a visible anterior cervical tumor, nodullary and voluminous, for nine years. After surgical treatment, the anatomical pathology sample revealed that the mass was composed of several cervical lymph node metastatic lesions of a papillary thyroid carcinoma. We report the discovery of an uncommon papillary thyroid carcinoma manifestation, with a difficult initial diagnosis and presenting voluminous lymph node metastases.

Tratamiento del tumor de células gigantes con curetaje e injerto con hidroxiapatita porosa coralina HAP-200® / Treatment of the giant cells tumor with curettage and graft of porous coral hydroxyapatite HAP-200®

Se realizó la presentación de un caso con un tumor de células gigantes en el extremo distal del fémur derecho a nivel del cóndilo femoral interno. Se retira quirúrgicamente, previo estudio, donde se confirmó el diagnóstico a través de la biopsia. En dicho proceder se efectuó un raspado extenso de la lesión respetando la superficie articular del cóndilo femoral, rellenando la cavidad con la hidroxiapatita HAP-200 ®, sin necesidad de apoyar dicho acto con una osteosíntesis interna o externa, sólo con una calza de yeso por 6 semanas. El seguimiento del paciente ha sido, hasta la fecha, de 6 años y no se ha reportado ninguna recidiva o metástasis, con una osteointegración positiva del biomaterial, lográndose la curación ósea y una función articular sin restricción(AU)

We presented a case of a giant cells tumor in the distal end of the right thigh at the level of the internal femoral condyle. Previously studied, the tumor was surgically retired, and the diagnosis was established through the biopsy. In that procedure we carried out a lesion extended scrape respecting the join surface of the femoral condyle, filling the cavity with hydroxyapatite HAP-200®, being unnecessary to support it with an internal or external osteosynthesis, only with plaster wedge for 6 weeks. The patient´s follow-up has lasted for 6 years up to day, and no recidivism or metastasis has been reported, with a biomaterial positive osteointegration, achieving the bone healing and a join functioning without restriction(AU)

A case study using total en bloc sacrectomy and neuroanastomosis for sacral tumor.

PURPOSE: To study the oncological and functional outcomes of patients undergoing en bloc tumor excisions and neuroanastomosis for sacral tumors. METHODS: Five patients who underwent en bloc total sacrectomy and neuroanastomosis from January 2006 to August 2010 were observed. A procedure combining the anterior and posterior approach was used on these patients. Neuroanastomosis was performed after sacrectomy. Perioperative complications and postoperative functions in these patients were analyzed. RESULTS: All patients had partial or complete loss of bladder and bowel functions, foot plantar flexion weakness and increased residual urine volume after surgery. Three patients were ambulatory. After 6 months, four patients were disease-free, two patients reported slightly improved bladder and bowel functions, four patients could ambulate with a walking stick and the one patient with sarcoma had other metastases and died after 8 months. After 1 year, two patients reported improved bladder and bowel functions, one patient slightly improved bladder and bowel functions and there was no change in one patient. CONCLUSION: Successful neuroanastomosis of sacral nerve roots does not occur in all patients, but lower limb, bladder and bowel functions can improve with time after the surgery.

[Clinical characteristics and prognosis of three rare and poor-prognostic subtypes of primary liver carcinoma].

OBJECTIVE: To explore the clinicopathological features and prognostic factors of three rare and poor-prognostic pathological subtypes of primary liver carcinoma, and improve the clinical diagnosis and surgical treatment. METHODS: A retrospective analysis of clinicopathological data of 69 patients with rare pathological subtypes of primary liver carcinoma, diagnosed by postoperative pathology in our hospital from October 1998 to June 2013 was carried out. The data of 80 cases of common poorly differentiated hepatocellular carcinoma treated in the same period were collected as control group. Kaplan-Meier method was used to analyze the survival rate, and Cox proportional hazards model was used for prognostic analysis in the patients. RESULTS: Thirty-four cases were combined hepatocellular carcinoma and cholangiocarcinoma (CCC, 28 males, 6 females), with a median age of 52 years (range, 33 to 73). Ninteen cases were giant cell carcinoma (GCC, 16 males and 3 females), with a median age of 59 years (range, 38 to 66). Sixteen cases were sarcomatoid carcinoma (SC, 14 males and 2 females), with a median age of 57 years (range, 46 to 70). The survival analysis revealed that median survival time and the 1-, 3-, 5-year survival rates for these 3 groups were 20 months, 61.8%, 29.4%, and 20.6% in the CCC patients, 13 months, 52.6%, 31.6%, and 0% in the GCC patients, and 8 months, 31.3%, 0%, 0% in the SC patients, respectively. The median survival time and survival rate of the SC group were significantly lower than those of the other three groups (P < 0.05). However, in the SC group, the incidences of hilar lymph nodes metastasis, vascular tumor emboli and invasion of adjacent organs were significantly higher than those in the other three groups (P < 0.05). There were no statistically significant differences among the other three groups (P > 0.05). The levels of carcino-embryonic antigen were higher in the three rare subtype groups than that of the control group. The incidences of multiple tumors of the three rare subtype groups were higher than that of the control group (P < 0.05). Positive surgical margin was an independent unfavorable prognostic factor. CONCLUSIONS: The combined hepatocellular carcinoma and cholangiocarcinoma, giant cell carcinoma and sarcomatoid carcinoma have a poor prognosis. Among them sarcomatoid carcinoma is the most malignant and poor prognostic one. Radical resection is recommended.

A case report of anaplastic carcinoma of the pancreas with remarkable intraductal tumor growth into the main pancreatic duct.

We herein report a case of anaplastic carcinoma of the pancreas with remarkable intraductal tumor growth into the main pancreatic duct. A 76-year-old male was referred to our hospital for treatment of a pancreatic tumor. Preoperative examinations revealed a poorly defined tumor in the main pancreatic duct in the body of the pancreas, accompanied with severe dilatation of the main pancreatic duct, which was diagnosed as an intraductal papillary-mucinous neoplasm. We performed distal pancreatectomy and splenectomy. The pathological examination revealed that the tumor consisted of a mixture of anaplastic carcinoma (giant cell type) and adenocarcinoma in the pancreas. There was a papillary projecting tumor composed of anaplastic carcinoma in the dilated main pancreatic duct. The patient is now receiving chemotherapy because liver metastasis was detected 12 mo after surgery. In this case, we could observe a remarkable intraductal tumor growth into the main pancreatic duct. We also discuss the pathogenesis and characteristics of this rare tumor with specific tumor growth.

[Case of giant cell anaplastic ductal carcinoma of the pancreas].

A 56-year-old woman was admitted to our hospital with fever and systemic malaise. Abdominal computed tomography revealed an enhanced tumor of the pancreatic head, measuring 9cm in maximal diameter and containing a low-density area. Subtotal stomach-preserving pancreatoduodenectomy was performed. Hemorrhage and necrosis were evident within the tumor, and osteoclastic polynuclear giant cells were also identified. A diagnosis of giant cell anaplastic ductal carcinoma of the pancreas was made. The patient has been free from recurrence for 6 months since surgery.

Mammary carcinoma with osteoclast-like giant cells: a case report.

Mammary carcinoma with osteoclast-like giant cells is rare, and comprises less that 2% of breast carcinoma cases. Herein, we present a case of a 45-year-old woman who underwent breast lumpectomy and sentinel lymph node biopsy for a solitary well defined breast tumor. Histological examination revealed an invasive tumor composed of ducts, small nests and cribriform formations intermixed with a prominent osteoclast like giant cell component. The background stroma is hemorrhagic with conspicuous hemosiderin deposition. The paper will outline the clinico-pathologic characteristic features of this uncommon subtype as well as the current understanding on the pathogenesis of the osteoclast-like giant cells. The invasive carcinoma and the osteoclast-like giant cells staining patterns using immunohistochemical stains for estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, receptor activator of nuclear-kB, RANK ligand, and matrix metalloproteinase 1 are reported.

Polyomavirus (BK)-associated pleomorphic giant cell carcinoma of the urinary bladder: a case report.

This report describes the morphological features of a pleomorphic giant cell carcinoma with focal trophoblastic differentiation of the urinary bladder in a male, 12 years post living related donor renal transplant. The voided urine cytology demonstrated rare decoy cells admixed with markedly atypical urothelial cell clusters, papillae and giant cells. Cystoprostatectomy demonstrated a nodular mass involving the trigone and right lateral-posterior wall, adjacent to the ureteral orifice. Hematoxylin-eosin stained sections showed two synchronous malignancies: (a) pleomorphic giant cell carcinoma with focal trophoblastic differentiation of the urinary bladder, metastatic to the omentum and (b) prostatic adenocarcinoma, Gleason score 3+4=7, involving the right prostate lobe. Strong diffuse expression of polyomavirus large T antigen was demonstrated in the primary and metastatic pleomorphic giant cell carcinoma, supporting a possible role for polyomavirus (BK) in the oncogenetic pathway. The prostatic adenocarcinoma was negative for polyomavirus large T antigen. Our findings of p63, CK7 and CK903 expression in pleomorphic giant cell carcinoma suggest that the tumor is of urothelial derivation. This is the first report describing the morphological features of urinary bladder pleomorphic giant cell carcinoma with trophoblastic differentiation, positive for polyomavirus large T antigen, arising in the background of BKV reactivation.

Treatment of giant basal cell carcinomas of the head and neck with aggressive resection and complex reconstruction.

Basal cell carcinoma is exceedingly common, but giant basal cell carcinomas (GBCCs) are rare. We retrospectively reviewed 34 patients with GBCC on the head and neck region treated with aggressive surgical excision and reconstruction in a single operative procedure.The large defects were reconstructed with 15 free tissue transfers and 20 pedicled muscle, musculocutaneous flaps, and skin flaps. We were able to observe 23 patients for a minimum 5 years after the surgery. Locoregional recurrence and/or distant metastasis were not observed in 22 patients. Only 1 patient with the scalp BCC had local recurrence between the flap and the normal tissue 2 years after the surgery. Recurrent tumor was widely excised and reconstructed with a skin graft. Our results imply that low complications, good oncologic control, and acceptable cosmetic results can be achieved by a 1-stage team approach with aggressive surgical resection and reconstruction.