Residual Pure Intralymphatic Breast Carcinoma Following Neoadjuvant Chemotherapy is Indicative of Poor Clinical Outcome, Even in Node-Negative Patients.

Residual carcinoma confined to lymphovascular spaces following neoadjuvant chemotherapy (NAC) for invasive breast carcinoma is an uncommon finding. We studied pathologic features and outcome for patients with pure intralymphatic carcinoma (PIC) following NAC, a pattern of residual disease reported to have a poor outcome in the only previously published series of this entity. Six of 284 (2.1%) patients treated with NAC were studied. All 6 patients had axillary lymph node involvement before NAC. Tumors were triple-negative (n=3) and HER2+ (n=3: 2 ER+, 1 ER-). Two patients presented with clinical findings of inflammatory carcinoma. Three of 5 pre-NAC core biopsies showed lymphovascular invasion. Three patients showed complete clinical response to NAC, and 3 showed partial response. Post-NAC surgical specimens showed foci of intralymphatic carcinoma in the breast spanning an extent of 0.5 mm to 0.5 cm. Residual ductal carcinoma in situ was present in 2 cases. Four of 6 patients converted to node-negative following NAC. One patient had distant metastasis at presentation and 1 patient died of pulmonary embolism 2 months after surgery. Three of the 4 remaining patients developed distant metastasis, of which 2 first recurred locally (in mean follow-up of 46.5 mo). Patients with PIC had significant greater risk for relapse (hazard ratio, 10.18 [1.97, 52.58]; P=0.006) compared with other NAC-treated patients, after controlling for residual lymph node involvement, tumor size, tumor subtype, histologic grade, and age. Residual PIC following NAC is associated with poor outcome, including in patients that are node-negative following NAC.

Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

DICER1 Mutations are Consistently Present in Moderately and Poorly Differentiated Sertoli-Leydig Cell Tumors.

Ovarian Sertoli-Leydig cell tumors (SLCTs) are uncommon sex cord-stromal tumors associated with both germ-line and somatic DICER1 mutations, the frequency of which has varied widely in different studies (0% to 62.5%). The current World Health Organization Classification includes 3 histologic types of SLCTs (well-differentiated, moderately differentiated, and poorly differentiated); heterologous elements and/or retiform patterns may be present in moderately and poorly differentiated neoplasms. We investigated the frequency of DICER1 mutations in a series of 38 ovarian tumors initially diagnosed as SLCTs, and explored whether identified mutations were associated with specific morphologic features. Specialist pathology review performed blinded to molecular results confirmed 34 tumors to be SLCTs (22 moderately differentiated, 8 poorly differentiated; 4 well-differentiated), while the remaining 4 neoplasms were considered not to represent SLCTs. Of the 34 cases diagnosed as SLCTs, 30 (88%) harbored >=1 DICER1 mutation. All 30 moderately differentiated/poorly differentiated SLCTs contained mutations, but we did not find deleterious DICER1 mutations in the 4 well-differentiated SLCTs. Our study reports the highest DICER1 mutation frequency to date in SLCTs, with 100% of moderately differentiated and poorly differentiated tumors being DICER1-mutated. This suggests that DICER1 mutation may be a defining feature of these neoplasms. Although the number of cases is limited, well-differentiated SLCTs appear to be DICER1-independent. Moderately differentiated and poorly differentiated SLCT components often coexist with each other and form part of a spectrum, while well-differentiated SLCTs usually occur in pure form, suggesting that fundamentally, these represent 2 separate and independent tumor types with a different pathogenesis. We suggest that all patients with ovarian SLCTs undergo germ-line DICER1 mutation testing.

Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

Proliferation index of different Gleason pattern 4 histomorphologies and associated pattern 3 adenocarcinoma of the prostate

Publication date: Available online 27 June 2017
Source:Human Pathology
Author(s): Liying Fu, Michael Hwang, Adebowale J. Adeniran, Peter A. Humphrey
Gleason grade is one of the most powerful prognostic indicators for adenocarcinoma of the prostate. A higher proliferation index of prostatic adenocarcinoma has been demonstrated in numerous studies to be significantly associated with more aggressive behavior. To date, the proliferation index of the different Gleason pattern 4 histomorphologies, including cribriform, fused glands, and poorly-formed glands, has not been determined. The aim of this investigation was to quantitate and compare the proliferation index, as assessed by Ki67 labeling index, of different Gleason pattern 4 histomorphologies. We also analyzed the Ki67 labeling index of Gleason pattern 3 adenocarcinoma associated with and without cribriform adenocarcinoma. Amongst Gleason pattern 4 morphologies, cribriform adenocarcinoma exhibited a higher mean proliferation index at 5.3% compared to fused gland adenocarcinoma at 3.9% (P = .03) and poorly-formed glands at 3.6% (P < .01). The mean Ki67 labeling index for Gleason pattern 3 associated with cribriform adenocarcinoma was higher at 4.1% compared to pure Gleason pattern 3 at 2.2% (P < .01) and Gleason pattern 3 associated with non-cribriform pattern 4 adenocarcinoma at 2.9% (P = .02). This higher proliferation index of Gleason pattern 3 adenocarcinoma associated with cribriform pattern 4 adenocarcinoma indicates that not all Gleason pattern 3 cells are identical and that cribriform adenocarcinoma may influence or be related to associated Gleason pattern 3. Gleason pattern 4 adenocarcinoma of the prostate with cribriform growth has a higher proliferation index than other grade 4 histomorphologies, consistent with the more clinically aggressive nature of cribriform adenocarcinoma of the prostate.

Anastomotic patterns of the facial parotid plexus (PP). A human cadaver study#

Publication date: Available online 27 June 2017
Source:Annals of Anatomy – Anatomischer Anzeiger
Author(s): Habib Bendella, Barbara Spacca, Svenja Rink, Hans-Jürgen Stoffels, Makoto Nakamura, Martin Scaal, Heide Heinen, Orlando Guntinas-Lichius, Roland Goldbrunner, Maria Grosheva, Doychin N. Angelov
Details of the human facial parotid plexus (PP) are not readily accessible during ordinary anatomical teaching because of insufficient time and difficulties encountered in the preparation. For parotid and facial nerve surgery however, precise knowledge of PP is of crucial importance. The aim of this study was therefore to provide more details of PP in anatomic specimens. Following anatomical dissection, its location, syntopy and morphology were analyzed in 158 cervico-facial halves of 95 cadavers. The facial nerve (FN) divides into a larger temporo-facial and a smaller cervico-facial trunk. Both trunks branch, form PP, and thus form connections along six distinctive anastomotic types. These anastomoses may explain why accidental or essential severance of a supposed terminal facial branch fails to result in the expected muscle weakness. However, whereas earlier anatomical and clinical studies report connections between both trunks in 67-90% of the cases, our data indicate the presence of anastomoses only in 44%. One reason for this difference may be found in our microscope-assisted dissection in infratemporal regions from which the parotid gland has been removed. Thereby we tracked both FN-trunks in both directions − distally and proximally − and determined the exact origin of all terminal FN branches. This lower rate of occurrence of connections between both trunks reduces the chances of luckily preserved muscle innervation and enhances the risk of facial palsy after transection of a terminal branch. Accordingly, precise anatomical knowledge on PP should be renewed and transection of facial nerve branches avoided.

The hypaxial origin of the epaxially located rhomboid muscles

Publication date: Available online 26 June 2017
Source:Annals of Anatomy – Anatomischer Anzeiger
Author(s): Minu Saberi, Qin Pu, Petr Valasek, Tannaz Norizadeh Abbariki, Ketan Patel, Ruijin Huang
In vertebrates, skeletal muscles of the body are made up of epaxial and hypaxial muscles based on their innervation and relative position to the vertebral column. The epaxial muscles are innervated by the dorsal branches of the spinal nerves and comprise the intrinsic (deep) back muscles, while the hypaxial muscles are innervated by the ventral branches of the spinal nerves including the plexus and consist of a heterogeneous group of intercostal, abdominal, and limb as well as girdle muscles. The canonical view holds that the epaxial muscles are derived from the medial halves of the somites, whereas the hypaxial muscles are all derived from the lateral somitic halves. The rhomboid muscles are situated dorsal to the vertebral column and therefore in the domain typically occupied by epaxial muscles. However, they are innervated by a ventral branch of the brachial plexus called the N. dorsalis scapulae. Due to the apparent inappropriate position of the muscle in relation to its innervation we investigated its origin to help clarify this issue. To study the embryonic origin of the rhomboid muscles, we followed derivatives of the medial and lateral somite halves using quail-chick chimeras. Our results showed that the rhomboid muscles are made up of cells derived mainly from the lateral portion of the somite. Therefore the rhomboid muscles which lie within the epaxial domain of the body, originate from the hypaxial domain of the somites. However their connective tissue is derived from both medial and lateral somites.

Massive tumor embolism in the abdominal aorta from pulmonary squamous cell carcinoma: Case report and review of the literature

Acute arterial tumor embolism is a rare complication in cancer patients. Most of the previously reported cases of arterial tumor embolism have been associated with pulmonary malignancies and occurred during the intraoperative and postoperative periods. Very few cases occurred spontaneously. To our knowledge, there is no previous report of spontaneous and massive tumor embolism occluding the abdominal aorta in patients suffering from primary pulmonary carcinoma. We describe the case of 64-year-old man who presented with left homonymous hemianopsia and backache. Further evaluation revealed a mass in the right lung, severe coagulopathy, and cerebral hemorrhagic infarction in the right occipital lobe. He suddenly developed lower limb ischemia 4 weeks after his first clinical visit, and finally, died of multiple organ failure. Autopsy showed non-keratinizing squamous cell carcinoma in the right lung and massive tumor emboli in the abdominal aorta containing nests of squamous cell carcinoma. Infarct regions were found in the bilateral kidneys, spleen, liver, and brain; fibrin thrombi, but not tumor emboli, were found in these regions. This case suggested that tumor embolism should be considered when patients suffering from primary pulmonary malignancies develop arterial embolism and arterial tumor emboli could be massive enough to occlude the abdominal aorta.