Pagets Disease of the Nipple

Right sided Paget's Disease

Left side normal nipple and areola

Hyperkeratosis right nipple and areola

A 15yr old girl presented to the clinic with complaints of itching in the nipple area of left breast for the past 2 years. She was shy to reveal her distress to her parents. She is otherwise healthy and has no family history of breast cancer. On examination, the whole of the nipple and areolar region was covered with hyperkeratotic plaques, but no oozing. No underlying lump was palpable. No axillary lymph node enlargement was seen. Plaques were sent off for cytological examination. She was advised to have a mammography and also to undergo a breast biopsy tomorrow.


Sir James Paget first described Paget disease (PD) of the breast in 1874. He reported a chronic eczematous disease on the skin of the nipple and the areola in 15 women, with an associated intraductal carcinoma of the underlying mammary gland.

 It is now widely accepted that mammary PD is always associated with an underlying carcinoma of the breast. By thorough histologic examination, Muir documented intraepidermal extension of malignant ductal epithelial cells through the lactiferous ducts and ductules into the epidermis (epidermotropism).^[2] The findings are the basis of the epidermotropic theory of mammary PD.





                                                                          nearly 100% of mammary PD cases are associated with an underlying carcinoma, either in situ
(intraductal, 10%) or infiltrating cancer (90%)
 In female patients with mammary PD, ages range from 24 to 84 years, with a mean age at diagnosis of 55 years; the average age range is 53-59 years. The average patient age is 5-10 years older for patients with mammary PD than for individuals with breast carcinoma.
 Mammary PD occurs almost exclusively in females; PD of the male breast is extremely rare


Survival is related to the presence or the absence of a palpable breast tumor. When present, the prognosis is the poorest. In one study, 31 (62%) of 50 patients with mammary PD presented with a detectable breast mass.
One half (50%) of patients with PD presenting with a palpable breast mass have associated axillary lymph node metastasis. Two thirds of patients with axillary node metastasis were reported to have a palpable breast mass, whereas one third of patients with axillary metastasis did not have a palpable mass.

Mastectomy is the standard treatment of mammary Paget disease. Conservative treatment with preservation of the nipple-areola complex results in a higher rate of recurrence than treatment by mastectomy.

Mammography changes include

• Subareolar microcalcifications (helpful in evaluating and locating clinically occult, nonpalpable underlying breast carcinoma)
• Architectural distortion
• Thickening of the nipple and the areola (reflecting edema)
• Nipple changes (in a minority of patients)
   
   
  Statistical evidence suggests that in the setting of negative mammography findings, magnetic resonance imaging (MRI) of the involved breast can detect otherwise occult PD and thus facilitate treatment planning for patients with PD.
   
   Scrape cytology has been suggested as a noninvasive and reliable, rapid diagnostic screening method for mammary PD
   
  Punch, wedge, or excisional biopsy of the lesional skin of the nipple-areola complex to include the dermal and subcutaneous tissue for detailed microscopic examination provides an adequate sample for the accurate diagnosis of mammary PD.  
  
  
  Tumorous Paget cells are negative for estrogen and progesterone receptor sites,
   
   Mammary Paget disease has been classified into 4 clinical stages.
  

  • Stage 0 - Lesion confined to the epidermis, without underlying in situ ductal carcinoma of the breast
  • Stage 1 - Associated with in situ ductal carcinoma just beneath the nipple
  • Stage 2 - Associated with extensive in situ ductal carcinoma
  • Stage 3 - Associated with invasive ductal carcinoma
     
     Mastectomy (radical or modified) and lymph node clearance are appropriate therapies for patients with mammary Paget disease (PD) with a palpable mass and underlying invasive breast carcinoma. As many as two thirds of patients are reported to have axillary lymph nodes positive for metastasis. Noninvasive breast carcinoma (in situ carcinoma) is found in about 65% of patients with mammary PD without a palpable mass
   

Ovarian Hyperstimulation Syndrome

                        A 24 year old lady presented to the nephrologist in our hospital with acute renal failure. She is nulliparous and was undergoing treatment for subfertility and IVF was planned. According to her history, as she failed to bring her records, she was given HMG for ovarian stimulation.  At time of egg collection, she was found to have mild ascites and enlarged ovaries. Eggs were retrieved and 3 embryos were transferred. She then developed dyspnea and renal failure. She also had 2.5L of ascites drained. She was transferred to our hospital.

                       On admission, Urine output was less than 300ml per day and she had developed ascites and dyspnea. Her full blood count revealed Hb of 8.6g/dl. platelets 4,30,000, hematocrit 30%. Electrolytes were within normal limits. Blood urea 42mg/dl, serum creatinine 4.8mg/dl. She underwent hemodialysis on the day of admission in acute medical care unit. Ultrasound scan revealed ascites, pleural effusion and massive enlargement of ovaries with normal looking endometrium. She improved symptomatically the next day. Her abdominal girth went down from 36cm to 32cm. Serum creatinine was still 4.3mg/dl. Hb 9.2g/dl, platelets 4,30,000/cumm. She was transferred to the ward. 

                       On the third day, her creatinine was 2.8mg/dl, abdominal girth was 29cm, no ascites on ultrasound scan. She was discharged with follow up in 4days with urea and creatinine and abdominal ultrasound scan to be repeated then.

Here are the scan pictures of her ovaries taken at admission. The right ovary is abdominal and 9.5cm in size and the left ovary is in the pouch of douglas and measures 6.5cm 

Left Ovary

Right Ovary

                       Ovarian hyperstimulation syndrome(OHSS) is particularly associated with injection of a hormone called hCG which is used for release of oocytes. The risk is further increased by multiple doses of hCG after ovulation and if the procedure results in pregnancy

Symptoms

                      In mild OHSS, patient complains of bloating sensation in the abdomen, nausea, diarrhea, weight gain

                      In moderate OHSS, excessive weight gain (weight gain of greater than 2 pounds per day), increased abdominal girth, vomiting, diarrhea, darker urine and less in amount, excessive thirst, and skin and/or hair feeling dry (in addition to mild symptoms). 

                      In Severe OHSS, symptoms are fullness/bloating above the waist, shortness of breath, pleural effusion, dark urine or anuria, calf and chest pains, marked abdominal distention, and lower abdominal pain can occur. 

It can also be classified according to the sizes of the ovaries, as they can go upto 12-15cm in size.

Pathophysiology  

                     In response to HCG for oocyte retrieval, there is hyperperfusion of the ovaries resulting in fluid shift to third space. The HCG given will result in multiple luteinised follicles which in turn lead to excess estrogen, progesterone and cytokines. There is excess production of vascular endothelial growth factor under the influence of HCG which is the cause for increased vascular permeability of ovaries.

Risk Factors

                     Young age, multiple follicular development, multiple doses of HCG

Complications

                     ovarian torsion, ovarian rupture, thrombophlebitis and renal failure can occur.

Treatment

                    In mild OHSS, supportive aand conservative treatment with monitoring of abdominal girth and clinical symptoms is all that is necessary.

In moderate OHSS, aspiration of pleural effusion or paracentesis may be necessary. monitoring of blood counts and electrolytes is necessary. Ultrasound scan for monitoring size of ovaries and strict maintenance of fluid input, output chart is essential.

In severe OHSS, posponement of embryo transfer is advised as severity of symptoms can be reduced.

Prevention

                    Use GnRH antagonists can eliminate the risk of OHSS, but there is slight decrease in success rate of IVF with this. Use of FSH should not be indiscriminate and HCG should be withheld in cases of suspicion.

Fibroid uterus causing retention of urine in a nullipara

Aerial view

Rt lateral view

Left lateral view

End-on view

                                                 A 30yr old nulliparous women presented with pain lower abdomen and inability to pass urine for > than 18hrs. She was treated elsewhere with diuretic and analgesia. Later she was catheterised and 1.5 litres of urine was obtained. On ultrasound scan she was found to have an anterior wall fibroid of size 6cm. She was offered a myomectomy, but insisted on a hyterectomy as she had taken an oath of celibacy and was dedicated to God and despite warnings of future problems of early onset menopause and its attendent risk of osteoporosis and heart disease, she was adamant about hysterectomy. The same was performed.

              Although common in men with prostatic disease, urinary retention is an uncommon condition in young women. Etiologies include anti-cholinergic use, detrusor muscle hypotony, infection, pregnancy, prolonged catheter use, myasthenia gravis and other neurologic diseases. Extrinsic causes include a retroverted uterus in pregnancy, large ovarian masses, hematocolpos, uterine prolapse and uterine fibroids. As urinary retention is an uncommon condition in young women, many physicians may have a difficult time making a timely diagnosis. As evidenced by the delay in diagnosis in our patients, Urologists may look for non-gynecologic causes of retention more commonly, and delay pelvic examinations. As pelvic organ etiologies are common causes of retention in women, this delay can lead to unnecessary invasive tests and patient suffering.

Although previously thought uncommon, patients frequently presented with urgency, frequency and intermittent retention prior to complete inability to void. Patients may present with urinary urgency and frequency, recurrent UTI, intermittent difficulty in voiding and defecating and complete and sudden urinary obstruction. Fibroids were commonly found projecting off the posterior uterus, and were often difficult to elevate from the cul-de-sac at the time of surgery because of pelvc impaction.

               Multiple theories have been proposed to explain the mechanism of urinary retention. One common theory describes the incarceration of posterior fibroids into the cul-de-sac causing compression of the urethra against the pubic bone. A large fibroid may weigh down the uterus, causing acute retroversion and compression of the cervix against the proximal urethra (1). This may cause anterior deflection of the cervix and subsequent urethral compression (2). As the fibroid enlarges and becomes incarcerated in the pelvis, the bladder can be stretched across the uterus also affecting function. Other causes of urgency and frequency include urethra elongation causing intermittent voiding dysfunction.
Treatment of urinary retention caused by fibroids includes placement of a pessary to elevate the bladder neck, gonadotropin-releasing hormone receptor agonists to decrease the size of the uterus, uterine artery embolization (UAE), myomectomy and hysterectomy. Although recommended as a treatment for retention and fibroids,  patient can have recurrence of her symptoms after UAE.


              Uterine fibroids that result in compression of the proximal urethra, elongation of the urethra and bladder, can cause voiding dysfunction and urinary retention in young women. These and other pelvic aetiologies should be considered in young women presenting with voiding dysfunction and urinary retention

Related citations

• Uterine fibroid embolization for patients with acute urinary retention. [J Vasc Interv Radiol. 2008]
• Acute urinary retention caused by a uterine leiomyoma: a case report. [J Reprod Med. 2004]
• Review Acute complications of fibroids. [Best Pract Res Clin Obstet Gyn...]
• Objective cure of urinary retention following laparoscopic hysterectomy for a large uterine fibroid. [Int Urogynecol J. 2010]
• Review Acute urine retention in early pregnancy resulting from fibroid incarceration: proposition for management. [Fertil Steril. 2008]

Diabetes insipidus in pregnancy

                      A 25 year old primigravida presented to the gastroenterologist at 26 weeks' gestation with complaints of 10-12 episodes of diarrhea and increased thirst for a duration of 2 months. No history of fever. She was apparently drinking about 8-10 L of water everyday and was still complaining of dryness of mouth and thirst and weakness. She was from a rural area with limited access to medical aid.
                      Day 1: She was referred to me to check on fetal status. Fetus was normal size and heart beat was around 150bpm.  A renal profile and complete blood count was requested. She was treated for gastroenteritis and blood sugar was 132mg/dl. Blood pressure was normal at 110/80mmHg. Amylase 62U/L(0-80), Urea 15mg/dl(15-40), Creatinine 0.5mg/dl(0.6-1.6), Hb 10.4g%(11-16.5), WCC 8,800/cumm(4000-11000). Na147mEq/L(135-146) and K 2.9mEq/L(3.5-5.5) and chloride 113mEq/L(95-105). By the end of first day of admission, she had one episode of diarrhea. Strict input/output chart was being maintained. Ultrasound scan showed a live intrauterine singleton pregnancy of 31 weeks' gestation, liver, GB, pancreas, kidneys were normal looking. Urine for ketone bodies was negative.In a 17hour period, she had passed, 3.5L of urine and intake was 5.8L.

                     Day 2: Electrolytes were repeated and by next morning she had 8 episodes of diarrhea, no vomitings and intake of fluids at 4litres in 9 hours. Stool and urine were sent for culture and sensitivity. Iron, calcium and antacids were stopped. Fluids were restricted to 2L per day on day2 as it has been observed that excess fluid intake can be a cause of diarrhea. Diarrhea continued, sodium was now raised at 154mEq/L and potassium at 3.3mEq/L, Chloride 123mEq/L. Urine and serum osmolality was requested. Urine osmolality was 77.6mosm/kg(300-850 mosm/kg). Serum osmolality was 396.2mosm/kg(280-295) Thyroid function tests were normal. She passed stools about 20times that day. Her urine was very clear on inspection. She was asked to restrict her fluid intake and staff were asked to give her a bedpan to pass stools to notice any abnormality. She was very desperate for water in the night to the point of being abusive to the hospital staff and her urine remained very dilute. Input 3.8L and output 2.9L.

                    Day 3: By morning, she started to get drowsy. Pt appeared very dehydrated. One episode of diarrhea at night. Passed urine 3 times. Electrolytes were repeated urgently and sodium was 190mEq/L, potassium 3.2mEq/L. She was developing cerebral edema due to electrolyte imbalance. She was given 1/2 NS, Frusemide 40mg iv. Urine output was 1.8L, very dilute.Rapid infusion of fluids in Intensive care was started. 2.5L of half normal saline with a potassium sparing diuretic, Spironolactone was given and Desmopressin (DDAVP) nasal spray was started. Blood gases were done at 8am: pH:7.3, pCO2 17mmHg, pO2 107mmHg, Na 180 mEq/L, K 3.7mEq/L. Ultrasound scan  repeated showed intrauterine fetal death. Repeat electrolytes showed Na 163, K 4.2, Cl 134. Input 7.6L, Urine output 3.8L. She continued to have polydipsia despite oral fluid intake of 0.9L and IV fluids of 4L. Lungs were clear. DDAVP was given as 20µg each nostril. By 8pm she was stable and was having tightenings of the uterus.  At midnight,Electrolytes Na 143, K 3.4, Cl 113

                   Day 4: At 6 am, Electrolytes Na 143, K 3.8, Cl 114 Misoprostol induction of labour was started at 9am and she went on to deliver a stillborn female baby at 5pm. Thirst was reduced. Input: 5.3L, Output:L 3.7L.

                  Day 5: DDAVP was continued. Electrolytes Na 142, K 3.1,Urine output 70-150ml/hr.Input 1.25L, Output 1.1L. A diagnosis of Diabetes insipidus in pregnancy was made. Her diarrhea was due to excess water intake.

                                         She was discharged on the sixth day after admission. She was warned of recurrence in next pregnancy and to seek early medical attention. 

                     Diabetes insipidus is a very rare condition and even rarer in pregnancy with an approximate incidence of 1 in 30,000 pregnancies. These women have either decreased central secretory reserve or impaired renal responsiveness to vasopressin. In addition, women can experience diabetes insipidus de novo in pregnancy through the actions of placental vasopressinase, which causes accelerated degradation of vasopressin. This form of diabetes insipidus may be associated with increased complications of pregnancy, including preeclampsia. DDAVP cannot be degraded by placental vasopressinase and is the treatment of choice.

Painful Fibroid Uterus

A 38yr old lady presented with a history of pain lowers abdomen on and off for three months but constant for the past 20days. She has had 3 normal vaginal deliveries. No significant past medical history. On examination per abdomen, she was found to have an 18-19 weeks size uterus, which was tender on palpation.vaginal examintion showed cervix pulled up. Intraoperatively, she was seen to have a 8cm fibroid to the left of the fundus. Procedure was uneventful. When the uterus was bisected, there was softening at the centre., probably some hyaline degeneration. non pregnant fibroids are generally speaking painless. If they are painful, degeneration, torsion of a pedunculated fibroid, pressure on adjacent organs or malignant change is suspected.