Evolution of a refractory prolactin-secreting pituitary adenoma into a pituitary carcinoma: report of a challenging case and literature review

Abstract Background Pituitary carcinomas (PCs), defined as distant metastases of pituitary neoplasms, are very rare malignancies. Because the clinical presentation of PCs is variable, early diagnosis and management remain challenging. PCs are always refractory to comprehensive treatments, and patients with PCs have extremely poor prognoses. Case presentation We describe one case of a prolactin-secreting pituitary adenoma (PA) refractory to conventional therapy that evolved into a PC with intraspinal metastasis. A 34-year-old female was diagnosed with an invasive prolactin-secreting PA in 2009 and was unresponsive to medical treatment with bromocriptine. The tumor was gross totally removed via transsphenoidal surgery (TSS). However, the patient experienced multiple tumor recurrences or regrowth despite comprehensive treatments, including medical therapy, two gamma knife radiosurgeries (GKSs), and four frontal craniotomies. In 2016, she was found to have an intradural extramedullary mass at the level of the fourth lumbar vertebra. The intraspinal lesion was completely resected and was confirmed as a metastatic PC based on histomorphology and immunohistochemical staining. The literature on the diagnosis, molecular pathogenesis, treatment, and prognosis of patients with prolactin-secreting PCs was reviewed. Conclusion PCs are very rare neoplasms with variable clinical features and poor prognosis. Most PCs usually arise from aggressive PAs refractory to conventional therapy. There is no reliable marker to identify aggressive PAs with a risk for progression to PCs; thus, it is difficult to diagnose these PCs early until the presence of metastatic lesions. It is still very challenging to manage patients with PCs due to a lack of standardized protocols for diagnosis and treatment. Establishing molecular biomarkers and the pathobiology of PCs could help in the early identification of aggressive PAs most likely to evolve into PCs.

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Real-life use of talimogene laherparepvec (T-VEC) in melanoma patients in centers in Austria, Switzerland and Germany

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-001701 ◽

2021 ◽

Vol 9 (2) ◽

pp. e001701

Author(s):

Julia Maria Ressler ◽

Matthias Karasek ◽

Lukas Koch ◽

Rita Silmbrod ◽

Joanna Mangana ◽

...

Keyword(s):

Chart Review ◽

Progressive Disease ◽

Overall Response Rate ◽

Real Life ◽

Retrospective Chart Review ◽

Distant Metastases ◽

Complete Response ◽

Talimogene Laherparepvec ◽

Metastatic Lesions ◽

Melanoma Patients

BackgroundTalimogene laherparepvec (T-VEC) is a licensed therapy for use in melanoma patients of stage IIIB-IVM1a with injectable, unresectable metastatic lesions in Europe. Approval was based on the Oncovex Pivotal Trial in Melanoma study, which also included patients with distant metastases and demonstrated an overall response rate (ORR) of 40.5% and a complete response (CR) rate of 16.6%.ObjectivesThe aim of this study was to assess the outcome of melanoma patients treated with T-VEC in a real-life clinical setting.MethodsBased on data from 10 melanoma centers in Austria, Switzerland and southern Germany, we conducted a retrospective chart review, which included 88 patients (44 male, 44 female) with a median age of 72 years (range 36–95 years) treated with T-VEC during the period from May 2016 to January 2020.Results88 patients fulfilled the inclusion criteria for analysis. The ORR was 63.7%. 38 patients (43.2%) showed a CR, 18 (20.5%) had a partial response, 8 (9.1%) had stable disease and 24 (27.3%) patients had a progressive disease. The median treatment period was 19 weeks (range: 1–65), an average of 11 doses (range: 1–36) were applied. 39 (45.3%) patients developed adverse events, mostly mild, grade I (64.1%).ConclusionThis real-life cohort treatment with T-VEC showed a high ORR and a large number of durable CRs.

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A Review of the Literature on Extrarenal Retroperitoneal Angiomyolipoma

International Journal of Surgical Oncology ◽

10.1155/2016/6347136 ◽

2016 ◽

Vol 2016 ◽

pp. 1-19 ◽

Cited By ~ 3

Author(s):

Anthony Kodzo-Grey Venyo

Keyword(s):

Radical Nephrectomy ◽

De Novo ◽

Treatment Options ◽

Distant Metastases ◽

Surgical Excision ◽

Radical Resection ◽

Malignant Tumours ◽

Selective Embolization ◽

Metastatic Lesions ◽

Benign Tumours

Background. Extrarenal retroperitoneal angiomyolipomas are rare.Aim. To review the literature.Results. Angiomyolipomas, previously classified as hamartomas, are now classified as benign tumours. Thirty cases of primary retroperitoneal angiomyolipomas have been reported. Diagnosis of the disease upon is based radiological and pathological findings of triphasic features of (a) fat and (b) blood vessels and myoid tissue. Immunohistochemistry tends to be positive for HMB45, MART1, HHF35, calponin, NKI-C3, and CD117. The lesion is common in women. Treatment options have included the following: (a) radical surgical excision of the lesion with renal sparing surgery or radical nephrectomy in cases where malignant tumours could not be excluded and (b) selective embolization of the lesion alone or prior to surgical excision. One case of retroperitoneal angiomyolipoma was reported in a patient 15 years after undergoing radical nephrectomy for angiomyolipoma of kidney and two cases of distant metastases of angiomyolipoma have been reported following radical resection of the tumour.Conclusions. With the report of two cases of metastases ensuing surgical resection of the primary lesions there is need for academic pathologists to debate and review angiomyolipomas to decide whether to reclassify angiomyolipomas as slow-growing malignant tumours or whether the reported cases of metastases were de novo tumours or metastatic lesions.

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Identification of Independent Primary Tumors and Intrapulmonary Metastases Using DNA Rearrangements in Non–Small-Cell Lung Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2014.56.7644 ◽

2014 ◽

Vol 32 (36) ◽

pp. 4050-4058 ◽

Cited By ~ 56

Author(s):

Stephen J. Murphy ◽

Marie-Christine Aubry ◽

Faye R. Harris ◽

Geoffrey C. Halling ◽

Sarah H. Johnson ◽

...

Keyword(s):

Lung Cancer ◽

Distant Metastases ◽

Small Cell ◽

Genomic Rearrangements ◽

Next Generation ◽

Primary Tumors ◽

Histologic Subtype ◽

Metastatic Lesions ◽

Mate Pair ◽

Clinical Dilemma

PurposeDistinguishing independent primary tumors from intrapulmonary metastases in non–small-cell carcinoma remains a clinical dilemma with significant clinical implications. Using next-generation DNA sequencing, we developed a chromosomal rearrangement–based approach to differentiate multiple primary tumors from metastasis.MethodsTumor specimens from patients with known independent primary tumors and metastatic lesions were used for lineage test development, which was then applied to multifocal tumors. Laser capture microdissection was performed separately for each tumor. Genomic DNA was isolated using direct in situ whole-genome amplification methodology, and next-generation sequencing was performed using an Illumina mate-pair library protocol. Sequence reads were mapped to the human genome, and primers spanning the fusion junctions were used for validation polymerase chain reaction.ResultsA total of 41 tumor samples were sequenced (33 adenocarcinomas [ADs] and eight squamous cell carcinomas [SQCCs]), with a range of three to 276 breakpoints per tumor identified. Lung tumors predicted to be independent primary tumors based on different histologic subtype did not share any genomic rearrangements. In patients with lung primary tumors and paired distant metastases, shared rearrangements were identified in all tumor pairs, emphasizing the patient specificity of identified breakpoints. Multifocal AD and SQCC samples were reviewed independently by two pulmonary pathologists. Concordance between histology and genomic data occurred in the majority of samples. Discrepant tumor samples were resolved by genome sequencing.ConclusionA diagnostic lineage test based on genomic rearrangements from mate-pair sequencing demonstrates promise for distinguishing independent primary from metastatic disease in lung cancer.

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Papillary thyroid microcarcinoma: distinct form or cancer growth stage?

Endocrine Surgery ◽

10.14341/serg12696 ◽

2021 ◽

Vol 14 (4) ◽

pp. 19-25

Author(s):

Vladimir A. Solodkiy ◽

Dmitri K. Fomin ◽

Dmitri A. Galushko ◽

Hayk G. Asmaryan

Keyword(s):

Univariate Analysis ◽

Central Zone ◽

Distant Metastases ◽

Papillary Thyroid Microcarcinoma ◽

Papillary Thyroid ◽

The Past ◽

Thyroid Microcarcinoma ◽

Metastatic Lesions ◽

Thyroid Capsule

Background. Over the past decades an increase in the incidence of papillary thyroid microcarcinoma (PTMC) has been observed throughout the world owing to the improved diagnostics. There are many different opinions about the aggressiveness degree of this group of tumors, as well as about the tactics of managing patients with PTMC.Aim of the study is the identification of the prognostic factors responsible for the features of the clinical course, including the more aggressive one.Materials and methods. A study was carried out with a detailed analysis of a group of patients with papillary thyroid cancer ≤1 cm in size and the existing clinical data of regional and distant metastases. All patients underwent thyroidectomy with bilateral central cervical lymph node dissection. Factors such as gender, patient age, bilaterality, extrathyroid extension, the presence or absence of a capsule around the tumor node, the absence or presence of metastases in the central part were assessed. In 26.6% histological examination revealed metastatic lesions of the central group lymph nodes. Latent metastases were detected in 24.2% of women and 43% of men, in 36.7% of patients <55 and in 14.3% of patients ≥ 55 years, in 29.5% with the absence of the node capsule and in 19.3% with encapsulated tumors, in 48.1% with multicentric growth and in 19.5% with a solitary neoplasm, in 21.7% with a tumor size ≤0.5 cm and in 27.9% with a node of 0.6–1 cm, in 24% with the absence of invasion of the thyroid capsule and in 31% with the presence of extrathyroid invasion, in 21% of patients with typical, in 26% with follicular and 43% with mixed papillary cancer. 95 patients received radioiodine therapy. No additional metastases were found in them.Results. When conducting univariate analysis, the main signs influencing the development of metastases in the central zone were age up to 55 years (p = 0.009, χ2 = 6.919) and multicentric neoplasm (p = 0.004, χ2 = 8.530); in multivariate analysis, similarly, age younger 55 years (p = 0.000, Exp B = 0.011, CI 95.0% 0.001–0.106) and multifocality (p = 0.027, Exp B = 2.686, CI 95.0% 1.119–6.448).Conclusion. PTMC is not a separate group or tumor morphotype, and the determination of treatment tactics for this group of patients should be based not only on the size of the tumor, but on the clinical and biological parameters of the tumor.

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Multiple Cutaneous Metastases as Initial Presentation in Advanced Colon Cancer

Case Reports in Gastrointestinal Medicine ◽

10.1155/2018/8032905 ◽

2018 ◽

Vol 2018 ◽

pp. 1-3 ◽

Cited By ~ 1

Author(s):

Sudheer Nambiar ◽

Asha Karippot

Keyword(s):

Advanced Colorectal Cancer ◽

Clinical Manifestations ◽

Colon Adenocarcinoma ◽

Distant Metastases ◽

Cutaneous Metastasis ◽

Ascending Colon ◽

Visceral Metastasis ◽

Cutaneous Metastases ◽

Advanced Colon Cancer ◽

Metastatic Lesions

Skin metastases from advanced colorectal cancer are relatively rare and occur most often when the cancer is advanced, following the spread to other organs. Cutaneous metastases occur in about 3% of advanced colorectal cancers. We present an extremely rare case of a 68-year-old woman with advanced ascending colon adenocarcinoma that presented with multiple rapidly progressing painless cutaneous metastatic lesions with no other distant metastases. Of all the tumors, breast cancer most commonly spreads as cutaneous metastasis is followed by lung, colorectal, renal, ovarian, and bladder cancers. Cutaneous metastases can present in a variety of clinical manifestations, such as a rapidly growing painless dermal or subcutaneous nodule with intact overlying epidermis or as ulcers. In cases where the cutaneous deposit is isolated, as in visceral metastasis, there is a role for radical management such as wide local excision and reconstruction. In our patient, since she had multiple cutaneous metastases she began treatment with palliative systemic combination chemotherapy.

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A Rare Case of Metastatic Transformation to Pituitary Carcinoma

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1153 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A565-A566

Author(s):

Walter K Woznick ◽

Ashley Engel ◽

Diana Maas

Keyword(s):

Radiation Therapy ◽

Pituitary Adenoma ◽

Vision Loss ◽

Patient Adherence ◽

Pituitary Carcinoma ◽

Immunoperoxidase Staining ◽

Frontal Lesion ◽

Pituitary Mass ◽

Metastatic Lesions ◽

Pituitary Carcinomas

Abstract Background: Pituitary carcinomas are rare and comprise less than 0.5% of pituitary tumors and frequently arise from previously resected and/or radiated infiltrating adenomas.1 Radiation therapy is used to prevent regrowth but does not have significant data supporting improved prognosis.2 True pituitary carcinomas requires the presence of craniospinal and/or systemic metastases. Here, we present a case of benign pituitary adenoma that had progressed to a metastatic tumor and responded to radiation therapy. Clinical Case: Our patient was first diagnosed in 1982 with a pituitary mass after undergoing an MRI due to right eye blindness. He ultimately had a transcranial resection of the tumor and post-operative external radiation to residual tumor. Final pathology was consistent with a nonsecretory tumor. Additionally, he was diagnosed with panhypopituitarism and he was treated accordingly. Due to barriers of patient adherence, only one post-operative MRI was obtained, and he was lost to endocrine follow up. In 2007, he was again referred to endocrinology for new vision loss in the left eye. An MRI revealed a 3.0 x 3.8 x 4.4 cm tumor that compressed the optic chiasm. Additionally, multiple lesions were seen within the dural and leptomeningeal extra-axial areas including the largest left frontal lesion of 2.4 cm and a 1.7 cm lesion posterior to the cord within the foramen magnum. The patient underwent endonasal transsphenoidal resection of the sellar mass and biopsy of the frontal lesion in October 2007. Pathology showed pituitary adenocarcinoma in both the sellar and frontal lesions and immunoperoxidase staining was negative for all hormones. He completed salvage radiation to the sellar and craniospinal lesions in December 2007. MRI scans completed 7 months later showed stable residual pituitary and metastatic lesions. The patient received 6-month MRI screening exams for the first 2 years and then annually thereafter, as well as PET scanning, without significant progression or new metastatic lesions. Conclusion: We present a case of benign pituitary adenoma which transformed following resection to a malignant tumor with metastatic lesions in the brain and spinal cord that was treated with radiation with relative success. Despite the often-aggressive nature of these metastatic tumors, the patient has experienced a successful treatment course with minimal side effects and without progression 13 years after initial treatment of the metastatic pituitary carcinoma.

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Absent p53 Immunohistochemical Staining in a Pituitary Carcinoma

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100052902 ◽

2001 ◽

Vol 28 (2) ◽

pp. 174-178 ◽

Cited By ~ 14

Author(s):

Krishna Kumar ◽

Robert J.B. Macaulay ◽

Michael Kelly ◽

Tyler Pirlot

Keyword(s):

Pituitary Adenoma ◽

Chromogranin A ◽

P53 Protein ◽

Pituitary Hormones ◽

Pituitary Carcinoma ◽

Nuclear Accumulation ◽

Protein Accumulation ◽

Pituitary Neoplasms ◽

Null Cell ◽

Cranial Nerve Palsies

ABSTRACT:Background:Carcinomatous transformation of pituitary adenomas is uncommon, and is generally accompanied by nuclear accumulation of p53 protein. Pituitary carcinoma lacking accumulation of p53 protein is very rare, only two such cases being previously reported.Methods:A patient presented with visual disturbance and cranial nerve palsies and was found to have a suprasellar mass. He underwent both transphenoidal and transfrontal excision of a nonfunctioning pituitary adenoma which recurred several times. The third recurrence was accompanied by multiple dural-based metastases. Despite aggressive surgical management, he continued to develop additional intracranial lesions and died two years after the discovery of metastatic disease. Specimens from 1984, 1995, 1997 and 1998 were available for histological and immunocytochemical analysis. Antibodies recognizing the pituitary hormones (ACTH, PRL, GH, FSH, LH and TSH), as well as cytokeratin, epithelial membrane antigen (EMA), glial fibrillary acidic protein (GFAP) and chromogranin A were applied to investigate the lineage of the neoplasm. Antisera specific for Ki-67 (MIB-1) and p53 protein were also applied to further delineate the biology of the tumour.Results:Although cytokeratin and chromogranin A were detected in neoplastic cells, no expression of pituitary hormones was demonstrable, indicative of a nonfunctioning, null-cell pituitary adenoma. Nuclear pleomorphism and mitotic activity increased with subsequent resections. Abnormal accumulation of p53 protein was not observed, neither in early resections nor in the metastatic deposits.Conclusions:Failure to demonstrate p53 protein accumulation does not ensure a favourable outcome for pituitary adenoma. Accordingly, pituitary carcinoma may occur in the absence of p53 accumulation. The factors which underlie aggressive behaviour of pituitary neoplasms are uncertain but are under investigation.

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Bmi-1 Regulates Snail Expression and Promotes Metastasis Ability in Head and Neck Squamous Cancer-Derived ALDH1 Positive Cells

Journal of Oncology ◽

10.1155/2011/609259 ◽

2011 ◽

Vol 2011 ◽

pp. 1-16 ◽

Cited By ~ 51

Author(s):

Cheng-Chia Yu ◽

Wen-Liang Lo ◽

Yi-Wei Chen ◽

Pin-I Huang ◽

Han-Shui Hsu ◽

...

Keyword(s):

Stem Cells ◽

Tumor Volume ◽

Distant Metastases ◽

Cancer Stemness ◽

Snail Expression ◽

Metastatic Lesions ◽

Squamous Cancer ◽

Regulation Mechanisms ◽

Putative Marker ◽

Hnscc Patient

Recent studies suggest that ALDH1 is a putative marker for HNSCC-derived cancer stem cells. However, the regulation mechanisms that maintain the stemness and metastatic capability of HNSCC-ALDH1+cells remain unclear. Initially, HNSCC-ALDH1+cells from HNSCC patient showed cancer stemness properties, and high expression of Bmi1 and Snail. Functionally, tumorigenic properties of HNSCC-ALDH1+cells could be downregulated by knockdown of Bmi-1. Overexpression of Bmi-1 altered in expression propertyALDH1−cells to that ofALDH1+cells. Furthermore, knockdown of Bmi-1 enhanced the radiosensitivity of radiation-treated HNSCC-ALDH1+cells. Moreover, overexpression of Bmi-1 in HNSCC-ALDH1−cells increased tumor volume and number of pulmonary metastatic lesions by xenotransplant assay. Importantly, knock-down of Bmi1 in HNSCC-ALDH1+cells significantly decreased distant metastases in the lungs. Clinically, coexpression of Bmi-1/Snail/ALDH1 predicted the worst prognosis in HNSCC patients. Collectively, our data suggested that Bmi-1 plays a key role in regulating Snail expression and cancer stemness properties of HNSCC-ALDH1+cells.

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Clinicopathologic and Prognostic Association of GRP94 Expression in Colorectal Cancer with Synchronous and Metachronous Metastases

International Journal of Molecular Sciences ◽

10.3390/ijms22137042 ◽

2021 ◽

Vol 22 (13) ◽

pp. 7042

Author(s):

Sumi Yun ◽

Sukmook Lee ◽

Ho-Young Lee ◽

Hyeon Jeong Oh ◽

Yoonjin Kwak ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Infiltrating Lymphocytes ◽

Distant Metastases ◽

Significant Heterogeneity ◽

Metastatic Lesions ◽

Group Survival ◽

Metastatic Sites ◽

Infiltrating Lymphocytes ◽

Prognostic Association ◽

Metachronous Metastases

Patients with advanced colorectal cancer (CRC) with distant metastases have a poor prognosis. We evaluated the clinicopathological relevance of GRP94 expression in these cases. The immunohistochemical expression of GRP94 was studied in 189 CRC patients with synchronous (SM; n = 123) and metachronous metastases (MM; n = 66), using tissue microarray; the association between GRP94 expression, outcome, and tumor-infiltrating lymphocytes (TILs) was also evaluated. GRP94 was expressed in 64.6% (122/189) patients with CRC; GRP94 positivity was found in 67.5% and 59.1% patients with SM and MM, respectively. In the SM group, high GRP94 expression was more common in patients with a higher density of CD4+ TILs (p = 0.002), unlike in the MM group. Survival analysis showed that patients with GRP94 positivity had significantly favorable survival (p = 0.030); after multivariate analysis, GRP94 only served as an independent prognostic factor (p = 0.034; hazard ratio, 0.581; 95% confidence interval, 0.351–0.961) in the SM group. GRP94 expression was detected in 49.4% of metastatic sites and showed significant heterogeneity between primary and metastatic lesions (p = 0.012). GRP94 is widely expressed in CRC with distant metastases; its expression was associated with favorable prognosis in the SM group, unlike in the MM group.

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Neuroendocrine Carcinoma of the Larynx and Pharynx: A Clinical and Histopathological Study

Cancers ◽

10.3390/cancers13194813 ◽

2021 ◽

Vol 13 (19) ◽

pp. 4813

Author(s):

Primož Strojan ◽

Robert Šifrer ◽

Alfio Ferlito ◽

Cvetka Grašič-Kuhar ◽

Boštjan Lanišnik ◽

...

Keyword(s):

Early Stage ◽

Neuroendocrine Differentiation ◽

Distant Metastases ◽

Histopathological Study ◽

Prognostic Information ◽

Ki 67 ◽

Barr Virus ◽

Epstein Barr ◽

Reliable Marker ◽

Well Differentiated

Neuroendocrine carcinomas (NECs) of the head and neck are rare and the experience scanty. The Cancer Registry of Slovenia database was used to identify cases of laryngeal and pharyngeal NECs diagnosed between 1995–2020. Biopsies were analyzed for the expression of standard neuroendocrine markers (synaptophysin, chromogranin, CD56), INSM1, Ki-67, p16, and PD-L1 (using the combined positive score, CPS). In situ hybridization for human papillomavirus (HPV) and Epstein–Barr virus (EBV) was performed. Twenty patients (larynx, 12; pharynx, 8) were identified. One tumor was well differentiated (WD), five were moderately differentiated (MD), and 14 were poorly differentiated (PD). Disease control was achieved solely by surgery in 4/4 MD/PD T1-2N0-1 tumors. Eight patients died of the disease, seven of which were due to distant metastases. All three traditional markers were positive in 11/17 NECs and the INSM1 marker in all 20 tumors. Two of fourteen p16-positive tumors were HPV-positive, but all three nasopharyngeal NECs were EBV-negative. Three tumors had CPSs ≥ 1. In conclusion, INSM1 was confirmed to be a reliable marker of neuroendocrine differentiation. Except in WD and early-stage MD/PD tumors, aggressive multimodal therapy is needed; the optimal systemic therapy remains to be determined. p16, HPV, and EBV seem to bear no prognostic information.

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