Squamous cell carcinoma: pain as a clue to increased tumour diameter, increased invasion depth, the grade of differentiation, acantholysis and perineural invasion.

BACKGROUND: Pain may be associated with actinic keratosis (AK), intraepidermal carcinoma (IEC) and invasive squamous cell carcinoma (SCC), which may all display high-risk features. AIM: To examine variation in pain frequency associated with these three conditions, and assess their invasive SCC surface diameter, invasion depth, grade of differentiation, presence of acantholysis and perineural invasion (PNI). METHODS: Pain was prospectively recorded for consecutive cases of AK, IEC and SCC from three institutions in Australia during the period 2016-2018. RESULTS: Pain with palpation was recorded with 15.8% of AK (n = 30/190), 15.1% of IEC (n = 345/299) and 29.0% invasive SCC (n = 247/853). Pain without palpation was respectively 1.1% (2/190), 4.0% (12/299) and 6.7% (57/853). Invasive SCC with increased surface diameters and deeper invasion recorded increased pain frequency. Pain did not vary significantly by the grade of differentiation in males. In females, well-differentiated SCC recorded more pain (45.4%; n = 473) than poorly differentiated SCC (9.1%; n = 11). Acantholytic SCC recorded more pain 48.7% (n = 29) than nonacantholytic SCC 35.2% (n = 824). Three out of five cases of PNI recorded pain. Pain intensity was not recorded, which was a limitation. CONCLUSION: Pain presence increases from AK to invasive SCC. Pain was more frequent in invasive SCC with increased surface diameter, deeper invasion, acantholysis and PNI. Pain frequency did not vary between the grades of differentiation in males. In females, pain was less frequent in poorly differentiated than in well-differentiated SCC.

Invasive squamous cell carcinoma: comparison of differentiation grade and tumour depth by anatomical site in 1666 tumours.

BACKGROUND: Invasive squamous cell carcinomas (SCCs) presents with different grades of differentiation and depths of invasion. AIM: To compare the grade of differentiation, tumour diameter and tumour depth by anatomical site in invasive SCC. METHODS: Retrospective clinical and histopathological data on consecutive cases of SCC came from a clinic in Sydney, Australia were assessed. A multinomial logistic regression model was applied to compare grades of differentiation by age, sex, anatomical sites, and histological tumour maximum diameter and depth. RESULTS: In total, 1666 SCCs were identified, including 82.1% (n = 1367) well-differentiated, 13.3% (n = 222), moderately differentiated and 4.6% (n = 77) poorly differentiated SCCs. Patients with poorly differentiated tumours were more likely to be older and male (both P < 0.001). The most common site for poor differentiation was the scalp in men (n = 12; 15.6%) and the cheek or chin in women (n = 7; 9.1%). In the multivariate model, compared with well-differentiated SCC, older age was significantly associated with poorly and moderately differentiated SCC (P < 0.01 and P = 0.02, respectively). Larger tumour diameters were related to poor differentiation (P = 0.03). Ear, forehead and chest sites had increased tumour depth and poor differentiation. CONCLUSIONS: This study found increased rates of poorly differentiated SCC on the forehead and cheek for both sexes, while men displayed increased rates of poorly differentiated SCC on the bald scalp and the ears. Tumour diameter and depth increased as tumours varied from well-differentiated to moderately differentiated and from moderately differentiated to poorly differentiated. An increase in depth and increased prevalence of poorly differentiated tumours were found on the ears for men and on various facial sites for both sexes.

Acantholytic invasive squamous cell carcinoma: tumor diameter, invasion depth, grade of differentiation, surgical margins, perineural invasion, recurrence and death rate.

BACKGROUND: Squamous cell carcinoma (SCC) may present with or without the feature of acantholysis. METHODS: Investigate invasive acantholytic SCC by microscopic maximum tumor surface diameter, depth of invasion, grade of differentiation, perineural invasion (PNI) and percentage of acantholysis. Assess recurrence following excision. RESULTS: A total of 1658 consecutive invasive SCC cases were examined, comprising 4.9% acantholytic SCC. Median tumor microscopic maximum diameter was 8 mm for acantholytic SCC and 7.3 mm for non-acantholytic SCC. Median tumor invasion depth was 1.0 mm for acantholytic SCC and 1.5 mm for non-acantholytic SCC. Well, moderate and poor differentiation were not significantly different between acantholytic SCC and non-acantholytic SCC. One PNI case was found in 82 acantholytic SCC cases. A total of 77 acantholytic SCC cases were followed up over a median 25 months finding histologic proven recurrence at three acantholytic SCC excision sites. CONCLUSIONS: Acantholytic SCC were more likely to be located on head sites with less median depth than non-acantholytic SCC. Increasing percentage of acantholysis within acantholytic SCC was not associated with a shift towards poor differentiation. Histologic margins of 1.2 mm may adequately excise small acantholytic SCC. No recorded deaths, low PNI and low recurrence rates suggests acantholytic SCC is low-risk.

Pine oil effects on chemical and thermal injury in mice and cultured mouse dorsal root ganglion neurons.

A commercial resin-based pine oil (PO) derived from Pinus palustris and Pinus elliottii was the major focus of this investigation. Extracts of pine resins, needles, and bark are folk medicines commonly used to treat skin ailments, including burns. The American Burn Association estimates that 500,000 people with burn injuries receive medical treatment each year; one-half of US burn victims are children, most with scald burns. This systematic study was initiated as follow-up to personal anecdotal evidence acquired over more than 10 years by MH Bhattacharyya regarding PO's efficacy for treating burns. The results demonstrate that PO counteracted dermal inflammation in both a mouse ear model of contact irritant-induced dermal inflammation and a second degree scald burn to the mouse paw. Furthermore, PO significantly counteracted the tactile allodynia and soft tissue injury caused by the scald burn. In mouse dorsal root ganglion neuronal cultures, PO added to the medium blocked adenosine triphosphate-activated, but not capsaicin-activated, pain pathways, demonstrating specificity. These results together support the hypothesis that a pine-oil-based treatment can be developed to provide effective in-home care for second degree burns.

Effect of airway disease on blood gas exchange in racehorses.

Inflammatory Airway Disease (IAD), exercise-induced pulmonary hemorrhage (EIPH), and upper airway obstruction (UAO) are common respiratory tract diseases that can decrease performance. The purpose of this retrospective study was to compare bronchoalveolar lavage fluid cytology and arterial blood gas analysis during a treadmill test by poorly performing racehorses presented to Purdue University. One hundred thirty-two horses with a history of poor performance were included in this study. Ten horses with no history or diagnosis of EIPH, IAD, or UAO served as controls. Horses were evaluated by rhinolaryngoscopy for upper airway abnormalities and underwent a standardized treadmill test, and samples were collected for blood gas analysis. Horses with IAD or EIPH had a more severe exercise-induced hypoxemia, (mean+/-SD; 84.8+/-1.5 and 86.0+/-1.7 mm Hg average Pao2, respectively), than horses in the control group (92.8+/-2.1 mm Hg). The average Pao2 of horses with only UAO (88.3+/-3.3 mm Hg) was not significantly different from control horses. Gas exchanges were the most severely impaired in horses affected with both EIPH and UAO because they exhibited the lowest Pao2 and highest Paco2 values (66.5+/-15.2 and 52.2+/-6.3 mm Hg, respectively).

In situ hybridization of parathyroid hormone-related protein in normal skin, skin tumors, and gynecological cancers using digoxigenin-labeled probes and antibody enhancement.

We describe a novel procedure for in situ hybridization that combines the use of digoxigenin-labeled oligonucleotide probes with an antibody enhancement step that can be performed on formalin-fixed, paraffin-embedded tissues. Addition of a second antibody enhances the visibility of parathyroid hormone-related protein (PTHrP) mRNA expression from barely to highly discernible and interpretable, with virtually no nonspecific background expression. This technique has allowed visualization of PTHrP mRNA in normal human skin and epithelium-derived tumors. PTHrP mRNA expression was confined to the basal and spinous keratinocyte layers of skin. There was strong hybridization in the spinous keratinocyte layer and a low level of hybridization in the basal layer. An extensive panel of positive and negative controls included poly d(T) probe to indicate total mRNA present in the sections. Squamous cell carcinomas and basal cell carcinomas of the skin, from pathology archives, were examined for the presence of PTHrP mRNA. The results reflected previous immunohistochemical studies, with every squamous cell carcinoma hybridizing strongly with the PTHrP probes. The basal cell carcinomas showed no expression of PTHrP mRNA, although the total mRNA signal was very strong. The localization of PTHrP mRNA in the tumors of the gynecological tract also reflected the immunohistochemical findings, with expression found in the squamous cell carcinomas but not in the adenocarcinomas. In situ hybridization with digoxigenin-labeled oligonucleotide probes and antibody enhancement has provided a sensitive, highly specific procedure for detection of PTHrP mRNA in tumors and normal tissue.

Pigmented pheochromocytomas of the adrenal medulla.

Three primary pigmented pheochromocytomas of the adrenal gland are presented. The pigment in all cases proved to be melanin. Two of the pheochromocytomas were sporadic and histologically typical, except for a focal spindle cell configuration in one. It is believed that the morphologic appearance of these tumors represents divergent differentiation from neural crest, expressing typical pheochromocytoma (polygonal cells) and melanocytic features (melanin pigment).

Cholecystitis, cholelithiasis, and ganglioneuromatosis of the gall bladder: an unusual presentation of MEN type 2b.

A 40 year old man with multiple endocrine neoplasia type 2b (MEN 2b) presented with cholecystitis caused by gall stones. Twenty four years earlier, he had had a partial thyroidectomy for a cold nodule. At his initial presentation MEN 2b with medullary carcinoma of the thyroid had not been made. This was diagnosed while investigating his gall bladder symptoms and he was found to have asymptomatic residual medullary thyroid carcinoma and bilateral adrenal phaeochromocytomas. The cholecystectomy specimen contained several mixed calculi and extensive ganglioneuromatosis with large, prominent nerves containing ganglion cells in the gall bladder wall.

Testicular germ cell tumor with pineal metastases.

A patient with a mixed testicular germ cell tumor (choriocarcinoma, teratocarcinoma and embryonal carcinoma) that had metastasized to the lungs, cerebrum, and pineal gland is presented. The metastases had resulted in localized neurological signs and initially, on clinical grounds, a primary intracranial lesion could not be excluded. The occurrence of tumor metastases to the pineal gland is discussed and the literature is reviewed.

Leiomyosarcoma of the thyroid: immunohistochemical and ultrastructural study.

A primary leiomyosarcoma of the thyroid was seen in a 54 yr old female. The patient had a solitary, cold nodule with no abnormalities of thyroid function tests. Histologically it was composed of characteristic interlacing fascicles of spindle cells which, electron microscopically, showed thin myofilaments with focal dense bodies. Immunohistochemistry showed a strong reaction with vimentin, smooth muscle actin and desmin. No epithelial differentiation was noted immunohistochemically or ultrastructurally. No tumor recurrence was detected 15 mths after surgery. It is postulated that the smooth muscle differentiation had arisen by metaplastic change or de-differentiation with re-differentiation of anaplastic thyroid carcinoma.

Pseudocysts of the adrenal gland.

Three cases of pseudocysts or hemorrhagic cysts of the adrenal gland were encountered in female patients who presented with loin pain. The adrenalectomy specimens contained cystic structures; 2 had fibrous walls containing organizing blood clot, the remaining lesion was thin walled and contained blood stained fluid. Fat, normal adrenal cortical tissue and calcification were found within the cysts. These lesions (arising from vascular anomalies) require separation from hemorrhagic adrenal neoplasms. Awareness of adrenal pseudocysts and careful attention to the histological features aids this distinction.

Primary small cell carcinoma of the pancreas.

A 59 yr old male presented with abdominal pain and jaundice. CT scan showed a tumor in the pancreas with secondaries in the liver, peri-pancreatic lymph nodes, vertebral bone marrow and subcutaneous tissue of the neck together with a cervical lymph node. The patient died after 2 wks and autopsy revealed complete replacement of the pancreas by tumor. Careful dissection of both lungs failed to show any tumor. A diagnosis of primary small cell carcinoma of the pancreas was made. Review of the literature indicates that this type of carcinoma accounts for about 1% of all pancreatic cancers and is commoner in elderly males who have a history of cigarette smoking. There is usually a rapid progression of disease and widespread dissemination, especially if untreated. Some success has been obtained with chemotherapy.

Papillary cystadenocarcinoma of the appendiceal stump with mucocele and peritoneal metastases.

A 54-year-old Polynesian male developed a mucocele of the appendiceal stump 25 years after appendicectomy. Scattered peritoneal deposits up to 0.4 cm in diameter were also identified at laparotomy, and these were confined to the right iliac fossa. The cyst was excised with a right hemicolectomy and histology showed a mucus-producing papillary cystadenocarcinoma arising in the unburied appendiceal stump. There was invasion of the cyst wall and the peritoneal nodules contained metastatic tumour acini. The patient is well 12 months after surgery. This is a case of a rare tumour arising uniquely in an appendiceal stump and producing a mucocele. The term mucocele is discussed and recommendations made for its usage in pathological diagnosis.

The effects of comfrey derived pyrrolizidine alkaloids on rat liver.

Three groups of young adult rats were fed pyrrolizidine alkaloids derived from Russian comfrey to study the effects of the herb on the liver. Group I animals received a single dose of 200 mg/kg body wt, Group II 100 mg/kg three times a week for 3 weeks and Group III 50 mg/kg three times a week for 3 weeks. All rats showed light and electron-microscopic evidence of liver damage, the severity of which was dose dependent. There was swelling of hepatocytes and hemorrhagic necrosis of perivenular cells. There was a concomitant loss of sinusoidal lining cells with disruption of sinusoidal wall and the sinusoids were filled with cellular debris, hepatocyte organelles and red blood cells. Extravasation of red blood cells was evident. Terminal hepatic venules were narrowed by intimal proliferation, and in Group II and III, reiculin fibres radiated from these vessels. These appearances have been described in veno-occlusive disease due to pyrrolizidine alkaloids from other plant sources such as Senecio and Crotalaria. The safety of comfrey, a widely used herb, in relation to human consumption requires further investigation.

Fine-needle aspiration of cystic nephroma (multilocular cyst of the kidney).

Cystic nephromas are rare tumors of the kidney most commonly affecting boys or adult females. The fine-needle aspiration cytomorphology has not yet been described. A renal cystic mass in a 56 year old female was aspirated under ultrasound guidance. Papanicolaou stained smears of the cyst fluid revealed markedly atypical cells forming papillary clusters. Subsequent nephrectomy showed a typical cystic nephroma with lining epithelium resembling that seen in the aspirate. The cytomorphology of cystic nephroma has been misdiagnosed as renal cell carcinoma in the literature. Low cellularity, absence of necrosis, and paucity of single cells are features that should raise the possibility of cystic nephroma in a cystic renal mass.

Acetate and propionate impact on the methanogenesis of landfill leachate and the reduction of clogging components.

Synthetic leachate with different initial concentrations of acetate (500-2500 mg HAc/L) and propionate (500-3500 mg HPr/L) was treated with active biomass acclimated to landfill leachate under anaerobic mesophilic conditions for 72 h. Methanogenesis was observed within all samples during the first 48 h. The greatest removal of acetate (80-100%) and propionate (15-35%) was achieved in tests with initial concentrations ranging from 1500 to 190 0mg HAc/L and from 1000 to 1800mgHPr/L. Concurrent with the removal of acids, pH increased between 0.3 and 0.45 units, to above the threshold pH for precipitation of CaCO(3). Therefore, some 50-70% of dissolved Ca(2+) was removed from solution. This study suggests that by using an equalization tank (prior to the anaerobic digester) to maintain the acetate and propionate concentrations to within their optimum range would help to alleviate clogging through the removal of dissolved Ca(2+) and maximizing CH(4) production.